MX2008015918A - Compounds for the treatment of periodontal disease. - Google Patents

Abstract

Compounds, compositions and methods are provided which are useful in the treatment of periodontal disease.

Description

COMPOUNDS FOR THE TREATMENT OF PERIODONTAL DISEASE BACKGROUND OF THE INVENTION Bacterial infections of the mouth include inflammation of the gums, gingivitis and inflammation of the periodontium, periodontitis. Tartar bacteria and bacterial toxins that accumulate below the gum line can cause inflammation of the gums, called gingivitis. The inflammation of the gingiva comprises the influx of lymphocytes and macrophages in the tissue of the gingiva and its release of proinflammatory cytokines (TNFa and ILlb) and matrix metalloproteases (M P). Periodontitis, or pyorrhea, is a disease that involves chronic inflammation of the gums (gingiva), which continues without warning for years and decades in a patient, which results in loss of connective tissue and / or bone that supports the teeth. It is the loss of bone around the teeth that differentiates these two oral inflammatory diseases. The loss of the surrounding bone, which holds the teeth in the jaw, can last for years resulting in the teeth loosening and falling out. While gingivitis is reversible with antibacterial and / or anti-inflammatory treatments and good oral hygiene, periodontitis is irreversible. However, progress can be stopped or significantly diminished with appropriate treatment. The ref . : 198468 Periodontitis is the second most important cause, after tooth loss, of tooth loss. The development of new compounds and methods for treating mouth infections, such as those comprising bacteria, viruses, fungi and / or parasites, would represent a significant advance in the art. This development, and others, have been addressed by the present invention. Brief Description of the Invention In a first aspect, the invention provides an oral care composition comprising a compound described herein. In an exemplary embodiment, the oral care composition is a member selected from a mouth rinse, dentifrice, liquid bleach, chewing gum, soluble or partially soluble or insoluble film or strip, wipe or wipe, implant, dental floss. In an exemplary embodiment, the oral care composition is a selected member of a toothpaste, prophylactic toothpaste, tooth enamel, gel, professional gel and other related products applied by dentists, as well as mouthwash, mouthwash, dental floss. , chewing gum, pill, tablet, edible food product. and similar. In an exemplary embodiment, the dentifrice is a selected member of a powder, a toothpaste and dental gel. In an example embodiment, the compound is present in a therapeutically effective amount. In an exemplary embodiment, the compound is present in an amount of about 0.1% by weight of the compound / weight of the oral care composition to about 5% by weight of the compound / weight of the oral care composition. In an exemplary embodiment, the compound is present in an amount of about 0.3% by weight of the compound / percent of the oral care composition at about 0.6% by weight of the compound / weight of the oral care composition. In an exemplary embodiment, the compound is present in the range of about (all percentages are given by weight of the compound / weight of the oral care composition) 0.3% to about 5%, including about 0.4%, about 0.6%, approximately 0. 8%, approximately 1%, approximately 1. 5%, about 2%, about 2.5%, about 3%, about 3.5%, about 4 %, and similar. In exemplary embodiments, the compound is present in the range of about 2% to about 10%. In exemplary embodiments, the compound is present in the range of about 2% to about 4%. In exemplary embodiments, the compound is present in the range of from about 2.5% to about 6%. In exemplary embodiments, the compound is present in the range of about 0.1% a approximately 1%. In another example embodiment, the compound has a structure according to one of the following formulas: wherein B is boron, 0 is oxygen, R * and R ** is each independently selected from substituted or unsubstituted (C 1 -C 4) alkyl, substituted or unsubstituted (C 3 -C 7) cycloalkyl, substituted or unsubstituted alkenyl, substituted alkynyl or unsubstituted, substituted or unsubstituted aralkyl, substituted or unsubstituted phenyl, and substituted or unsubstituted heteroaryl; z is 0 or 1 and when z is 1, A is CH, CR10 or N; D is N, CH, or -CR12; E is H, OH, alkoxy or 2- (morpholino) ethoxy, C02H or C02alkyl; m = 0-2; r is 1 or 2, and where when r is 1, G is = 0 (oxygen with double bond) and when r is 2, each G is independently H, methyl, ethyl or propyl; R12 is selected from (CH2) kOH (where k = 1, 2 or 3), CH2NH2, CH2NH2-alkyl, CH2N (alkyl) 2, C02H, CC ^ alkyl, CONH2, OH, alkoxy, aryloxy, SH, S-alkyl , S-aryl, S02N (alkyl) 2 S02NHalkyl, S02NH2, SC ^ alkyl, S03H, SCF3, CN, halogen, CF3, O2, NH2, 2 ° -amino, 3 ° -amino, NH2S02 and C0NH2, and where J is CR10 or N; R9, R10 and R11 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, (CH2) nOH (n = 2 to 3), CH2NH2, CH2NHalkyl, CH2N (alkyl) 2, halogen, CHO, CH = N0H , C02H, C02-alkyl, S-alkyl, SC ^ -alkyl, S-aryl, S02N (alkyl) 2, S02NHalkyl, S02NH2, NH2, alkoxy, CF3, SCF3, N02, S03H and OH, including salts thereof. In another example embodiment, the compound has a structure according to where m is 0. In another example embodiment, the compound has a structure according to In another example embodiment, E is OH, R9 is H and R * and R ** is independently selected from substituted or unsubstituted phenyl. In another exemplary embodiment, R * and R ** is independently selected from 4-alkyl, 3-halogen-phenyl and 4-halogen, 3-alkyl-phenyl. In another example embodiment, R * and R ** are -methyl, 3-chloro-phenyl. In another exemplary embodiment, the compound is a member selected from 3-hydroxypyridine-2-carbonyloxy-bis (3-chloro-4-methylphenyl) -borane or (3-hydroxy-piolinate acid (bis (3-chloro-4) ester. -methylphenyl) borinic acid, 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole and 5- (4-cyanophenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole. Another embodiment, the compound is 3-hydroxypyridine-2-carbonyloxy-bis- (3-chloro-4-methylphenyl) borane In another example embodiment, the compound is 3-hydroxypyridine-2-carbonyloxy-bis (3 -chloro-4-methylphenyl) -borane and the compound is present in an amount from about 0.1% w / w to about 5% w / w In another example embodiment, the compound is 3-hydroxypyridine-2 -carbonyloxy-bis- (3-chloro-4-methylphenyl) -borane and the compound is present in an amount of about 0.3% w / w to about 0.6% w / w In an exemplary embodiment, the compound described or in the present has antibacterial properties. In another exemplary embodiment, the compound described herein has anti-inflammatory properties. In a modality of example, the compound described herein has both antibacterial and anti-inflammatory properties. In an exemplary embodiment, the compound described herein has both antibacterial and anti-inflammatory properties, and is 3-hydroxypyridine-2-carbonyloxy-bis (3-chloro-4-methylphenyl) borane. In a second aspect, the invention provides a method for killing a microorganism or for inhibiting the growth of a microorganism, comprising contacting the microorganism with a therapeutically effective amount of a compound described herein, thereby annihilating or inhibiting the growth of the microorganism. In an exemplary embodiment, the microorganism is a selected member of the Actinobacillus species, Porphyromonas species, Tannrella species, Prevotella species, Eubacterium species, Treponema species, Bulleidia species, Mogibacterium species, Slackia species, Campylobacter species, Eikenella species, Peptostreptococcus, Peptostreptococcus species, Capnocytophaga species, Fusobacterium species, Porphyromonas species and Bacteroides species. In another example embodiment, the microorganism is a member selected from Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythensis, Prevotella intermedia, Eubacterium nodatum, Treponema denticola, Bulleidia extructa, Mogibacterium.

Timidum, Slackia exigua, Campylobacter rectus, Eikenella corrodens, Peptostreptococcus micros, Peptostreptococcus anaerobius, Capnocytophaga ochracea, Fusobacterium nucleatum, Porphyromonas asaccharolytica and Bacteroides forsythus. In another example embodiment, the compound for use in the method has a structure described above. In another exemplary embodiment, the compound for use in the method is a member selected from 3-hydroxypyridine-2-carbonyloxy-bis- (3-chloro-4-methylphenyl) -borane or (3-hydroxy-piolinate ester of bis ( 3-chloro-4-methylphenyl) borinic acid), 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole, and 5- (4-cyanophenoxy) -1,3-dihydro-1-hydroxy- 2, 1-benzoxazole. In another exemplary embodiment, the compound for use in the method is 3-hydroxypyridine-2-carbonyloxy-bis- (3-chloro-4-methylphenyl) -borane. In a third aspect, the invention provides a method for treating or preventing periodontal disease in a human or animal, which comprises administering to a human or animal a therapeutically effective amount of a compound described herein, thereby treating or preventing it. periodontal disease. In an exemplary embodiment, periodontal disease is a selected member of gingivitis, periodontitis and juvenile / acute periodontitis. In another example embodiment, the compound for use in the method has a structure described above. In other For example, the compound for use in the method is a member selected from 3-hydroxypyridine-2-carbonyloxy-bis- (3-chloro-4-methylphenyl) -borane or (3-hydroxy-piolinate ester of bis (3- chloro-4-methylphenyl) borinic acid), 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole, and 5- (4-cyanophenoxy) -1,3-dihydro-1-hydroxy-2, 1-benzoxazole. In another exemplary embodiment, the compound for use in the method is 3-hydroxypyridine-2-carbonyloxy-bis- (3-chloro-4-methylphenyl) -borane. In an exemplary embodiment, a compound for use in the compositions and methods described herein have the structure according to Formula I: wherein B is boron, Rla is a member selected from a negative charge, a salt counterion, H, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. M is a selected member of oxygen, sulfur and NR2a, R2a is a selected member of H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. J is a member selected from (CR3aRa) and CR5a, R3a, Ra, and R5a are members independently selected from H, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted aryl or unsubstituted, and substituted or unsubstituted heteroaryl. The index ni is an integer selected from 0 to 2. W is a member selected from C-0 (carbonyl), (CR6aR7a) mi and CR8a, R6a, R7a and R8a are members independently selected from H, cyano, substituted alkyl or unsubstituted, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. The index mi is an integer selected from 0 and 1. A is a selected member of CR9a and N. D is a selected member of CR10a and N. E is a selected member of CRlla and N. G is a selected member of CR12a and N, R9a, R10, Rlla and R12a are members independently selected from H, OR * a, NR * aR ** a, SR * a -S (0) R * a, -S (0) 2R * a, - S (0) 2NR * to R ** a, -C (0) R * a, -C (0) OR * a, -C (0) NR * to R ** a, nitro, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. Each R * a and R ** a are independently selected members of H, nitro, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl . The combination of nitrogens (A + D + E + G) is an integer selected from 0 to 3. A member selected from R3a, R4a and R5a and a member selected from R6a, R7a and R8a, together with the atoms to which they are united, they are optionally joined to form a ring of 4 to 7 members. R3a and R4a, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring. R6a and R7a, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring. R9a and R10a, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring. R10a and Rlla, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring. RUa and R12a, together with the atoms to which they are attached, optionally join to form a 4 to 7 member ring.

In an exemplary embodiment, a compound for use in the compositions and methods described herein has a structure according to formula IX: wherein the variables A, D, E and G are described elsewhere in the present. R20, R21 and R22 are independently selected from a negative charge, or a salt counterion, H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted heteroaryl or unsubstituted In an exemplary embodiment, a compound for use in the compositions and methods described herein have a structure according to Formula XI: where the variables R1, A, D, E, G, J, W and M are described in another part of the present. In an exemplary embodiment, the microorganism is involved in periodontal disease. In another example embodiment, the microorganism is a selected member of a virus, bacterium, fungus, yeast or parasite. In another example embodiment, the bacterium is a selected member of the Actinobacillus species. Porphyromonas species, Tannerella species, Prevotella species, Eubacterium species, Treponema species, Bulleidia species, Mogíbacterium species, Slackia species, Campylobacter species, Eikenella species, Peptostreptococcus species, Peptostreptococcus species, Capnocytophaga species, Fusobacterium species, Porphyromonas species and Bacteroides species. In another example embodiment, the bacterium is a member selected from Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythensis, Prevotella intermedia, Eubacterium nodatum, Treponema denticola, Bulleidia extructa, Mogybacterium timidum, Slackia exigua, Campylobacter rectus, Eikenella corrodens, Peptostreptococcus micros, Peptostreptococcus anaerobius, Capnocytophaga ochracea, Fusobacterium nucleatum, Porphyromonas asaccharolytica and Bacteroides forsythus. In a second aspect, the invention provides a method for treating or preventing periodontal disease in an animal, the method comprising administering to the animal a Therapeutically effective amount of a boron-containing compound described herein. In an example mode, the animal is a human. In another example embodiment, periodontal disease is a selected member of gingivitis, periodontitis, and juvenile / acute periodontitis. In a third aspect, the invention provides an oral care composition comprising a boron-containing compound described herein. This oral care composition can be used to treat periodontal disease. The aspects, advantages and additional objects of the present invention will be apparent from the detailed description that follows. Brief Description of the Tables Tables 1A through IB present the test results of various boron-containing compounds of the invention against several bacteria that are involved in periodontal disease. Tables 2A through 2J present exemplary compounds of the invention. Tables 3A to 3H present exemplary compounds of the invention. Detailed Description of the Invention Definitions and Abbreviations The abbreviations used herein have in general the conventional meaning within the techniques chemical and biological. "Compound of the invention" and "example compounds for use in the methods of the invention", are used interchangeably and refer to the compounds discussed herein, and pharmaceutically acceptable salts and prodrugs of these compounds. Where substituent groups are specified by their conventional chemical formulas, described from left to right, they also cover the chemically identical substituents, which will result from the writing of the structure from right to left, for example, -CH20- it is proposed that also cite -OCH2 -. The term "poly" as used herein means at least 2. For example, a polyvalent metal ion is a metal ion having a valence of at least 2. "Portion" refers to the radical of a molecule that binds to another portion. The symbol '/ W * ^ either as a link or presented perpendicular to a link, implies the point at which the portion presented to the rest of the molecule is bound. The term "alkyl", by itself or as part of another substituent, means, unless otherwise indicated, straight or branched chain, or cyclic hydrocarbon radical, or combination thereof, which may be saturated completely, mono- or poly-unsaturated and can include di- and multi-valent radicals, having the designated number of carbon atoms (ie, C1-C10 means from one to ten carbons). Examples of saturated hydrocarbon radicals include, but are not limited to, groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, sec-butyl, cyclohexyl, (cyclohexyl) methyl, cyclopropylmethyl , homologs and isomers of, for example, n-pentyl, n-hexyl, n-heptyl, n-octyl, and the like. An unsaturated alkyl group is one having one or more double bonds or triple bonds. Examples of unsaturated alkyl groups include, but are not limited to, vinyl, 2-propenyl, crotyl, 2-isopentenyl, 2- (butadienyl), 2,4-pentadienyl, 3- (1,4-pentadienyl), ethynyl, 1- and 3-propynyl, 3-butynyl and homologues and higher isomers. The term "alkyl", unless otherwise indicated, is also proposed to include those alkyl derivatives defined in more detail below, such as "heteroalkyl". Alkyl groups that are limited to hydrocarbon groups are called "homoalkyls". The term "alkylene" by itself or as part of other substituents means a divalent radical or derivative of an alkane, as exemplified, but not limited, by -CH2CH2CH2CH2-, and further includes those groups described below as "heteroalkylene" . Typically, an alkyl (or alkylene) group will have from 1 to 24 carbon atoms carbon, with those groups having 10 or fewer carbon atoms that are preferred in the present invention. A "lower alkyl" or "lower alkylene" is a shorter chain alkyl or alkylene group, which generally has eight or fewer carbon atoms. The terms "alkoxy", "alkylamino" and "alkylthio" (or thioalkoxy) are used in their conventional sense, and refer to those alkyl groups attached to the rest of the molecule by an oxygen atom, an amino group, or an atom of sulfur, respectively. The term "heteroalkyl", by itself or in combination with another term, means, unless otherwise indicated, a straight or branched, stable chain, or cyclic hydrocarbon radicals, or combinations thereof, consisting of the designated number of carbon atoms and at least one heteroatom. In an exemplary embodiment, the heteroatoms may be selected from the group consisting of B, O, N, and S, and wherein the nitrogen and sulfur atoms may be optionally oxidized and the nitrogen heteroatom may optionally be quaternized. The heteroatoms B, O, N and S can be placed in any interior position of the heteroalkyl group or in the position in which the alkyl group is attached to the rest of the molecule. Examples include, but are not limited to, -CH2-CH2-O-CH3, -CH2-CH2-NH-CH3, -CH2-CH2-N (CH3) -CH3, -CH2-S-CH2-CH3, - CH2-CH2, -S (O) - CH 3, -CH 2 -CH 2 -S (0) 2 -CH 3, -CH = CH-0-CH 3, -CH 2 -CH = N-OCH 3 and -CH = CH-N (CH 3) -CH 3. Up to two heteroatoms can be consecutive, such as, for example, ?? 2-??-??? 3. Similarly, the term "heteroalkylene" by itself or as part of other substituents means a divalent radical or heteroalkyl derivative, as exemplified, but not limited to, -CH2-CH2-S-CH2-CH2- and - CH2-S-CH2-CH2-NH-CH2-. For heteroalkylene groups, the heteroatoms may also occupy either or both of the chain terms (eg, alkyleneoxy, alkylenedioxy, alkyleneamino, alkylenediamino, and the like). Still optionally, for alkylene and heteroalkylene linking groups, orientation of the linking group is not implied by the direction in which the formula of the linking group is described. For example, the formula -C (0) 2R'- represents both -C (0) 2R'- and -R'C (0) 2-. The terms "cycloalkyl" and "heterocycloalkyl", by themselves or in combination with other terms, represent, unless otherwise indicated, cyclic versions of "alkyl" and "heteroalkyl", respectively. Additionally, for heterocycloalkyl, a heteroatom can occupy the position at which the heterocycle joins the rest of the molecule. Examples of cycloalkyl include, but are not limited to, cyclopentyl, cyclohexyl, 1-cyclohexenyl, 3-cyclohexenyl, cycloheptyl, and the like. Examples of heterocycloalkyl include, but are not limited to, 1- (1, 2, 5, 6-tetrahydropyridyl), 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-morpholinyl, 3-morpholinyl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien- 2- ilo, tetrahydrothien-3-yl, 1-piperazinyl, 2-piperazinyl and the like. The terms "halo" or "halogen", by themselves or as part of another substituent, mean, unless otherwise indicated, a fluorine, chlorine, bromine or iodine atom. Additionally, terms such as "haloalkyl" are proposed to include monohaloalkyl and polyhaloalkyl. For example, the term "halo (Ci-C4) alkyl" is intended to include, but is not limited to, trifluoromethyl, 2,2,2-trifluoroethyl, 4-chlorobutyl, 3-bromopropyl, and the like. The term "aryl" means, unless otherwise indicated, an aromatic, polyunsaturated substituent which may be a single ring or multiple rings (preferably 1 to 3 rings), which are fused together or linked in a manner covalent The term "heteroaryl" refers to aryl groups (or rings) containing from one to four heteroatoms. In an exemplary embodiment, the heteroatom is selected from B, N, O and S, wherein the nitrogen and sulfur atoms are optionally oxidized, and the nitrogen atoms are optionally quaternized. A heteroaryl group can be attached to the rest of the molecule through a heteroatom. Non-limiting examples of groups aryl and heteroaryl include phenyl, 1-naphthyl, 2-naphthyl, 4-biphenyl, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 3-pyrazolyl, 2-imidazolyl, 4-imidazolyl, pyrazinyl, 2-oxazolyl, 4- oxazolyl, 2-phenyl-4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidyl, 4-pyrimidyl, 5-benzothiazolyl, purinyl, 2-benzimidazolyl, 5-indolyl, 1-isoquinolyl, 5-isoquinolyl, 2-quinoxalinyl, 5-quinoxalinyl, 3-quinolyl, and 6-quinolyl. The substituents for each of the above aryl and heteroaryl ring systems are selected from the group of acceptable substituents described below. For brevity, the term "aryl" when used in combination with other terms (eg, aryloxy, arylthioxy, arylalkyl) include both aryl and heteroaryl rings as defined above. Thus, the term "arylalkyl" is intended to include those radicals in which an aryl group is attached to an alkyl group (eg, benzyl, phenethyl, pyridylmethyl, and the like) including those alkyl groups in which an alkyl group has been replaced. carbon atom (e.g., a methylene group) for example, by an oxygen atom (e.g., phenoxymethyl, 2-pyridyloxymethyl, 3- (1-naphthyloxy) propyl, and the like).

Each of the foregoing terms (eg, "alkyl", "heteroalkyl", "aryl" and "heteroaryl") is proposed to include both substituted and unsubstituted forms of the indicated radical. Preferred substituents are provided below for each type of radical. Substituents for the alkyl and heteroalkyl radicals (including those groups frequently referred to as alkylene, alkenyl, heteroalkylene, heteroalkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, and heterocycloalkenyl) are generically referred to as "alkyl group substituents", and may be one or more of a variety of groups selected from, but not limited to: -OR ', = 0, = NR', = N-OR ', -NR'R ", -SR', halogen, -0C (0) R \ -C (0) R ', -C02R', -CONR'R ", -0C (0) NR'R", -NR "C (0) R ', -NR'-C (0) NR" R ", -NR" C (0) 2R \ -NR-C (NR 'R "R" 1) = NR "", -NR-C (NR'R ") = NR'", -S (0) R ', -S (0) 2R \ -S (0) 2NR'R ", -NRS02R \ -CN and -N02 in a number that varies from zero to (2m' + l), where m 'is the total number of carbon atoms in this radical. R ', R' ', R' '' and R '' "each preferably independently refers to hydrogen, substituted or unsubstituted heteroalkyl, substituted aryl, for example, aryl substituted with 1-3 halogens, alkyl groups, substituted or unsubstituted alkoxy or thioalkoxy, or arylalkyl groups. When a compound of the invention includes more than one R group, for example, each of the R groups is selected independently how are each group R ', R' ', R' '' and R '' '' when it is present in more than one of these groups. When R 'and R "are joined to the same nitrogen atom, they can be combined with the nitrogen atom to form a 5, 6 or 7 membered ring. For example, -NR'R "is proposed to include, but not be limited to, 1-pyrrolidinyl and 4-morpholinyl. From the foregoing discussion of substituents, one skilled in the art will understand that the term "alkyl" is intended to include groups that include carbon atoms attached to different groups of hydrogen groups, such as haloalkyl (e.g., -CF3 and -CH2CF3 ) and acyl (e.g., -C (0) CH3 / C (0) CF3, C (0) CH2OCH3, and the like). Similar to the substituents described for the alkyl radical, the substituents for the aryl and heteroaryl groups are generically referred to as "aryl group substituents". The substituents are selected from, for example: halogen, -OR ', = 0, = NR', = N-OR ', NR'R ", -SR', -halogen, -0C (0) R ', -C (0) R \ -C02R ', -CONR'R ", -0C (0) NR'R", NR "C (0) R', -NR '-C (0) NR" R "', -NR "C (0) 2R ', -NR-C (NR' R" R "') = NR" ", -NR-C (NR'R") = NR "', -S (0) R ', - S (0) 2R ', -S (0) 2NR * R ", -NRS02R \ -CN and -N02, -R', -N3, -CH (Ph) 2, fluoro (Ci-C) alkoxy, and fluoro (Ci-C4) alkyl, in a number that varies from zero to the total number of open valencies in the aromatic ring system; and wherein R ', R ", R"' and R "'" are preferably selected independently of hydrogen, substituted alkyl and unsubstituted, substituted and unsubstituted heteroalkyl, substituted and unsubstituted aryl and substituted and unsubstituted heteroaryl. When a compound of the invention includes more than one R group, for example, each of the R groups is independently selected as each group R ', R ", R"' and R "" when more is present. from one of these groups. Two of the substituents may optionally be substituted on adjacent atoms of the aryl or heteroaryl ring with a substituent of the formula -TC (0) - (CRR ') qU-, wherein T and U are independently -NR-, -0- , -CRR'- or an individual bond, and q is an integer from 0 to 3. Alternatively, two of the substituents may optionally be substituted on adjacent atoms of the aryl or heteroaryl ring with a substituent of the formula -A- (CH2) rB-, where A and B are independently -CRR'-, -0-, -S-, -S (0) -, -S (0) 2-, -S (0) 2NR'- or an individual link, and r is an integer from 1 to 4. One of the individual links of the new ring formed in this way can optionally be replaced with a double link. Alternatively, two of the substituents on adjacent atoms of the aryl or heteroaryl ring can be optionally substituted with a substituent of the formula - (CRR ') SX- (CR "R" 1) d-, where syd are independently integers from 0 to 3, and X is -O-, -NR'-, -S-, -S (0) -, -S (0) 2-, or -S (0) 2NR'-. The substituents R, R ', R "and R"' are preferably selected in a manner independently of hydrogen or (Ci-C6) substituted or unsubstituted alkyl. "Ring" as used herein means a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. A ring includes fused portions of a ring. The number of atoms in a ring is typically defined by the number of members in the ring. For example, a "5 to 7 member ring" means that there are 5 to 7 atoms in the surrounding array. The ring optionally included a heteroatom. In this manner, the term "5- to 7-membered ring" includes, for example, pyridinyl and piperidinyl. The term "ring" further includes a ring system comprising more than one "ring", wherein each "ring" is independently defined as before. As used herein, the term "heteroatom" includes atoms other than carbon (C) and hydrogen (H). Examples include oxygen (0), nitrogen (N), sulfur (S), silicon (Si), germanium (Ge), aluminum (Al) and boron (B). The symbol "R" is a general abbreviation representing a substituent group selected from substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted cycloalkyl or unsubstituted and substituted or unsubstituted heterocycloalkyl groups. By "effective" amount of a drug, formulation, or permeant is meant a sufficient amount of an active agent to provide the desired local systemic effect. A "topically effective", "cosmetically effective", "pharmaceutically effective", or "therapeutically effective" amount refers to the amount of drug necessary to effect the therapeutic result. wanted. "Topically effective" refers to a material that, when applied to the skin, nail, hair, claw or hoof, produces a desired pharmacological result either locally at the site of application or systemically as a result of the transdermal passage. of an active ingredient in the material. "Cosmetically effective" refers to a material that, when applied to the skin, nail, hair, claw or hoof, produces a desired cosmetic result locally at the site of the application of an active ingredient in the material. The term "pharmaceutically acceptable salts" is intended to include salts of the compounds of the invention which are prepared with relatively non-toxic acids or bases, depending on the particular substituents found in the compounds described herein. When the compounds of the present invention contain functionalities When relatively acidic, base addition salts can be obtained by contacting the neutral form of these compounds with a sufficient amount of the desired base, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable base addition salts include sodium, potassium, calcium, ammonium, organic amino or magnesium salts, or a similar salt. When the compounds of the present invention contain relatively basic functionalities, acid addition salts can be obtained by contacting the neutral form of these compounds with a sufficient amount of the desired acid, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable acid addition salts include those derived from inorganic acids such as hydrochloric, hydrobromic, nitric, carbonic, monohydrogencarbon, phosphoric, monohydrogenphosphoric, dihydrogenphosphoric, sulfuric, monohydrogen sulfuric, hydridedic or phosphorous acid and the like, as well as the salts derived therefrom. of relatively non-toxic organic acids such as acetic, propionic, isobutyric, maleic, malonic, benzoic, succinic, suberic, fumaric, lactic, mandelic, italic, benzenesulfonic, p-tolylsulfonic, citric, tartaric, methanesulfonic and the like acids. Also included are salts of amino acids such as arginate and the like, and salts of organic acids such as glucuronic or galacturonic acids and the like (see, for example, example, Berge et al., Journal of Pharmaceutical Science 66: 1-19 (1977)). Certain specific compounds of the present invention contain both basic and acid functionalities that allow the compounds to be converted into either base or acid addition salts. The neutral forms of the compounds are preferably regenerated by contacting the salt with a base or acid and by spinning the compounds of origin in the conventional manner. The form of origin of the compound differs from the various salt forms in certain physical properties, such as solubility in polar solvents. In addition to salt forms, the present invention provides compounds that are in a prodrug form. Prodrugs of the compounds or complexes described herein easily undergo chemical changes under physiological conditions to provide the compounds of the invention. Additionally, prodrugs can be converted to the compounds of the present invention by chemical or biochemical methods in an ex vivo environment. Certain compounds of the present invention can exist in unsolvated forms as well as solvated forms, including hydrated forms. In general, solvated forms are equivalent to unsolvated forms and are encompassed within the scope of the present invention. Certain compounds of the present invention may exist in multiple crystalline or amorphous forms. In general, all physical forms are equivalent for the uses contemplated by the present invention and are intended to be within the scope of the present invention. Certain compounds of the present invention possess asymmetric carbon atoms (optical centers) or double bonds; racemates, diastereomers, geometric isomers and individual isomers are encompassed within the scope of the present invention. The compounds of the present invention may also contain unnatural proportions of atomic isotopes in one or more of the atoms that make up these compounds. For example, the compounds can be radiolabelled with radioactive isotopes, such as for example tritium (3H), iodine-125 (125I) or carbon-14 (1 C). All isotopic variations of the compounds of the present invention, whether radioactive or not, are intended to be encompassed within the scope of the present invention. The term "pharmaceutically acceptable carrier" or "pharmaceutically acceptable carrier" refers to any formulation or carrier medium that provides the appropriate distribution of an effective amount of an active agent as defined herein, that does not interfere with the activity's effectiveness. of the active agent, and that it is sufficiently non-toxic to the host or patient. The Representative carriers include water, oils, both vegetable and mineral, cream bases, lotion bases, ointment bases and the like. These bases include suspending agents, thickeners, penetration enhancers, and the like. Its formulation is well known to those skilled in the art of cosmetics and topical pharmaceuticals. Additional information regarding the carriers can be found at Remington: The Science and Practice of Pharmacy, 21st Ed., Lippincott, Williams & Wilkins (2005) which is incorporated herein by reference. "Pharmaceutically acceptable topical carrier" and terms. equivalents refer to pharmaceutically acceptable carriers, as described herein above, suitable for topical application. A liquid or inactive cream vehicle capable of suspending or dissolving active agents and having the properties of being non-toxic and non-inflammatory when applied to the skin, nail, hair, claw or hoof is an example of a pharmaceutically topical carrier acceptable. This term is specifically proposed to cover carrier materials approved for use also in topical cosmetics. The term "pharmaceutically acceptable additive" refers to preservatives, antioxidants, fragrances, emulsifiers, dyes and excipients known or used in the field of drug formulation and which do not interfere unduly with the effectiveness of the biological activity of the active agent, and that is sufficiently non-toxic to the host or patient. Additives for topical formulations are well known in the art and can be added to the topical composition, as long as they are pharmaceutically acceptable and not deleterious to epithelial cells or their function. Additionally, it should not cause deterioration in the stability of the composition. For example, inert fillers, anti-irritants, tackifiers, excipients, fragrances, or opacifiers, antioxidants, gel-forming agents, stabilizers, surfactants, emollients, coloring agents, preservatives, buffering agents, or other enhancers. of permeation, and other conventional components of topical or transdermal distribution formulations as are known in the art. The terms "improvement", "improvement of penetration" or "improvement of permeation" refer to an increase in the permeability of the skin, nail, hair, claw or hoof to a drug, to increase the speed at which the permeation is permeated. drug through the skin, nail, hair, claw or hoof. The improved permeation affected through the use of these enhancers or enhancers can be observed, for example, by measuring the rate of diffusion of the drug through the skin of the animal or human, the nail, the hair, the claw or of the hoof using a diffusion cell apparatus. A diffusion cell is described by Merritt et al., J of Controlled Relay, 1: 161-162 (1984). The term "permeation enhancer" or "penetration enhancer" proposes an agent or a mixture of agents, which, alone or in combination, acts to increase the permeability of the skin, nail, hair or hoof to a drug. The term "excipient" is conventionally known to mean carriers, diluents and / or vehicles used in the formulation of effective drug compositions for the intended use. The term "topical administration" refers to the application of a pharmaceutical agent to the external surface of the skin, nail, hair, claw or hoof, such that the agent crosses the external surface of the skin, nail, hair, claw or hoof and enters the underlying tissue. Topical administration includes application of the composition to the intact skin, nail, hair, claw or hoof, or to a broken, natural or open wound of the skin, nail, hair, claw or hoof. Topical administration of a pharmaceutical agent can result in limited distribution of the agent to the skin and surrounding tissues or when the agent is removed from the treatment area by the bloodstream, it can result in systemic distribution of the agent. The term "transdermal distribution" refers to the diffusion of an agent through the barrier of the skin, nail, hair, claw or hoof that results from topical administration or another application of a composition. The stratum corneum acts as a barrier and few pharmaceutical agents are able to penetrate intact skin. In contrast, epidermis and the dermis are permeable to many solutes and therefore drug absorption occurs more easily through the skin, nail, hair, claw or hoof that is eroded or otherwise peels the stratum corneum to expose the epidermis. The transdermal distribution includes injection or other distribution through any portion of the skin, nail, hair, claw or hoof or mucous membrane and absorption or permeation through the remaining portion. Absorption through the intact skin, nail, hair, claw or hoof can be improved by placing the active agent in a suitable pharmaceutically acceptable vehicle before application to the skin, nail, hair, claw or hoof. Passive topical administration may consist of applying the active agent directly to the treatment site in combination with emollients or penetration enhancers. As used herein, transdermal distribution is proposed to include permeation distribution through or beyond the integument, i.e., skin, nail, hair, claw or hoof. The term "microbial infection" refers to any infection of a host tissue by an agent infectious which includes, but is not limited to, viruses, bacteria, mycobacteria, fungi, and parasites (see, for example, Harrison's Principies of Infernal Medicine, pp. 93-98 (Wilson et al., eds., 12th ed., 1991) Williams et al., J of Medicinal Chem. 42: 1481-1485 (1999), where each one is incorporated as a reference in its entirety). The term "microbial infection" refers to any infection of a host tissue by an infectious agent that includes, but is not limited to, viruses, bacteria, mycobacteria, fungi and parasites (see, for example, Harrison's Principles of Infernal Medicine, pp. 93-98 (Wilson et al., Eds., 12th ed.1991), Williams et al., J of Medicinal Chem. 42: 1481-1485 (1999), each incorporated herein by reference in its entirety. "Biological medium" as used herein refers to both biological milieus.Examples in vitro "biological media" include, but are not limited to, cell culture, tissue culture, homogenates, plasma and blood. The MIC, or minimal inhibitory concentration, is the point where the compound stops more than 90% of the cell growth relative to an untreated control. Also of use in the present invention are the compounds that are espe poly- or multi-valent, which they include, for example, species such as dimers, trimers, tetramers, and higher homologs of the compounds of use in the invention or reactive analogs thereof. The poly- and multi-valent species can be assembled from a single species or more than one species of the invention. For example, a numerical construction can be "homo-dimeric" or "heterodimeric". Additionally, poly- and multi-valent constructs in which a compound of the invention or a reactive analogue thereof is linked to an oligomeric or polymeric structure (eg, polylysine, dextran, hydroxyethyl-starch and the like) are within the scope of the present invention. The structure is preferably polyfunctional (ie having an array of reactive sites for binding compounds of use in the invention). In addition, the structure can be derivatized with an individual species of the invention or more than a species of the invention. Additionally, the present invention includes the use of compounds within the subject set forth in the formulas contained herein, which are functionalized to give compounds having solubility in water that is improved relative to analogous compounds that are not similarly functionalized. In this manner, any of the substituents set forth herein can be replaced with analogous radicals having improved solubility in water.

For example, it is within the scope of the invention to replace a hydroxyl group with a diol, or an amine with a quaternary amine, hydroxyamine or similar portion more soluble in water. In a preferred embodiment, additional solubility is imparted to the water by substitution at a site not essential for the activity towards the editing domain of the compounds set forth herein with a portion that improves the water solubility of the parent compounds. Methods for improving the water solubility of organic compounds are known in the art. These methods include, but are not limited to, functionalization of an organic core with a permanently charged portion, for example, quaternary ammonium, or a group that is charged at a physiologically relevant pH, for example, carboxylic acid, amine. Other methods include attaching groups containing hydroxyl or amine to the organic core, for example, alcohols, polyols, polyethers, and the like. Representative examples include, but are not limited to, polylysine, polietiminimide, poly (ethylene glycol) and po 1i (pr opi 1 eng 1 i col). The proper chemistry and functionalization strategy for these compounds is known in the art. See, for example, Dunn, R. L., et al., Eds. POLYMERIC DRUGS AND DRUG DELIVERY SYSTEMS, ACS Symposium Series Vol. 469, American Chemical Society, Washington, D.C. 1991. I. Compounds Containing Boron This invention provides boron-containing compounds that are useful in the treatment of microorganisms located in the oral cavities of animals. The compounds are also useful in the treatment of periodontal disease. I. a.) Borinic Esters The invention comprises a compound having the structure according to the following formulas: wherein B is boron, O is oxygen, R * and R ** are each independently selected from (C1-C4) alkyl, substituted or unsubstituted, (C3 ~ C7) cycloalkyl, substituted or unsubstituted, substituted or unsubstituted alkenyl, alkynyl substituted or unsubstituted, substituted or unsubstituted aralkyl, phenyl substituted or unsubstituted, and substituted or unsubstituted heteroaryl. The index z is 0 or 1 and when z is 1, A is CH, CR10 or N. D is N, CH, or CR12. E is H, OH, alkoxy or 2- (morpholino) ethoxy, C02H or C02alkyl. The index m = 0-2, the index r is 1 or 2, and where when r is 1, G is = 0 (oxygen with double bond) and when r is 2, each G is independently H, methyl, ethyl or propyl. R12 is selected from (CH2) k0H (where k = 1, 2 or 3), CH2NH2, CH2NH-alkyl, CH2N (alkyl) 2, C02H, C02alkyl, C0NH2, OH, alkoxy, aryloxy, SH, S-alkyl, S -aryl, S02N (alkyl) 2 S02NHalkyl, S02NH2, S02alkyl, S03H, SCF3, CN, halogen, CF3, N02, NH2, 2-amino, 3-amino, NH2S02 and CONH2, and wherein J is CR10 or N. R9, R10 and R11 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, (CH2) nOH (n = 2 to 3), CH2NH2, CH2NHalkyl, CH2N (alkyl) 2, halogen, CHO, CH = NOH , C02H, C02-alkyl, S-alkyl, S02-alkyl, S-aryl, S02N (alkyl) 2, S02NHalkyl, S02NH2, NH2, alkoxy, CF3, SCF3, N02, S03H and OH, including salts thereof. In preferred embodiments of a form described herein, such as formula 1, 2a, 2b, 2c, or 2d, R * and / or R ** are the same or are different, preferably wherein one of R * and R ** is a substituted or unsubstituted (Ci-C4) alkyl or R * and R ** are each a substituted or unsubstituted (C1-C4) alkyl. In a preferred embodiment of a formula described herein, such as formula 1, 2a, 2b, 2c or 2d, R * and / or R ** are the same or are different, preferably wherein one of R * and R ** is a cycloalkyl (C3) -C7) substituted or unsubstituted or R * and R ** are each a substituted or unsubstituted (C3-C7) cycloalkyl. In a preferred embodiment of a formula described herein, such as formula 1, 2a, 2b, 2c or 2d, R * and / or R ** are the same or are different, preferably wherein one of R * and R ** is alkenyl substituted or unsubstituted by R * and R ** are each a substituted or unsubstituted alkenyl. In a preferred further embodiment thereof, the alkenyl has the structure 2 Where R1, R2, and R3 are each independently selected from the group consisting of hydrogen, alkyl, aryl, cycloalkyl, substituted aryl, aralkyl, substituted aralkyl, (CH2) kOH (where k = 1, 2 or 3), CH2NH2 , CH2NH-alkyl, CH2N (alkyl) 2, C02H, C02alkyl, COHN2, S-alkyl, S-aryl, S02alkyl, S02 (alkyl) 2, S02NHalkyl, S02NH2, SO3H, SCF3, CN, halogen, CF3 and N02. In a preferred embodiment of a formula described herein, such as formula 1, 2a, 2b, 2c or 2d, R * and / or R ** are the same or different, preferably wherein one of R * and R ** is a substituted or unsubstituted alkynyl or R * and R ** are each a substituted or unsubstituted alkynyl. In a further preferred embodiment thereof, the alkenyl has the structure 3 wherein R1 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, substituted aryl, aralkyl, substituted aralkyl (CH2) kOH (where k = 1, 2 or 3), CH2NH2, CH2NH-alkyl, CH2 (alkyl) 2, C02H, C02alkyl, COHN2, S-alkyl, S-aryl, S02alkyl, S02 (alkyl) 2 / S02NHalkyl, S02NH2, S03H, SCF3, CN, halogen, CF3 and N02. In a preferred embodiment of a formula described herein, such as formula 1, 2a, 2b, 2c or 2d, R * and R ** are the same or are different, preferably wherein one of R * and R ** is a substituted or unsubstituted phenyl or R * and R ** are each a substituted or unsubstituted phenyl but excluding compounds of formula 1 wherein z is 1, A is CR10, D is CR12, J is CR10 and excluding compounds of formula 2 wherein the combination of substituents is such that z is 1, A is CR10, D is CR12, m is 2, and G is H or methyl or ethyl. In a separate mode from the above, G is also not propyl. However, in specific modalities these compounds Excluded, although not claimed as new, may find use in one or more of the methods of the invention, preferably for treatment against infection, more preferably in treatment against fungal infection. In a preferred embodiment, only novel compounds of the invention are contemplated for these uses. The novel compounds of the invention do not include derivatives of quinaldine, such as 2-methylquinoline, wherein R9 is methyl, Az is CH, D is CH, J is CH and R11 is hydrogen. However, these compounds may be useful in the methods of the invention. A preferred embodiment is a compound of a formula described herein, such as formula 1, 2a, 2b, 2c, or 2d, wherein R * and R ** are each a phenyl or substituted phenyl. Another preferred embodiment is a compound of a formula described herein, such as formula 1, 2a, 2b, 2c or 2d, wherein one of R * or R ** is benzyl or substituted benzyl. A further preferred embodiment is a compound of a formula described herein, such as formula 1, 2a, 2b, 2c or 2d, wherein r is 1, G is = 0, m is 0 and E is OH. A preferred embodiment is a compound of a formula described herein, such as formula 1, 2a, 2b, 2c or 2d, wherein z is 1 and R9 is selected from alkyl (greater C), (CH2) nOH (n = 1, 2 or 3), CH2NH2, CH2NHalkyl, CH2N (alkyl) 2, CHO, CH = NOH, C02H, C02-alkyl, S-alkyl, S02-alkyl, S- aryl, alkoxy (greater than C4), SCF3, and N02. In a preferred embodiment, the compound has a formula described herein, such as formula 1, 2a, 2b, 2c, or 2d, wherein z is 1 and R10 is selected from alkyl (greater than C4), (CH2) nOH (n = 1, 2 or 3), CH2NH2, CH2NHalkyl, CH2N (alkyl) 2, CHO, CH = NOH, C02H, C02-alkyl, S-alkyl, S02-alkyl, S-aryl, alkoxy (greater than C2) , SCF3 and N02. In another preferred embodiment, the compound has a formula described herein, such as formula 1, 2a, 2b, 2c, or 2d, wherein z is 1 and D is CR12 wherein R12 is selected from (CH2) kOH (in where k = l, 2 or 3), CH2NH2, CH2NH-alkyl, CH2N (alkyl) 2, C02H, C02alkyl, CONH2, OH, alkoxy (greater than C4), aryloxy, SH, S-alkyl, S-aryl, S02alkyl , S03H, SCF3, CN, N02, NH2S02 and C0NH2. In a further preferred embodiment, the compound has a formula described herein, such as formula 1, 2a, 2b, 2c or 2d, wherein z is 1, E is N- (morpholinyl) ethoxy or alkoxy greater than C. Other preferred embodiments are compounds having the structure of a formula described herein, such as formula 1, 2a, 2b, 2c or 2d, wherein A or D is nitrogen, or wherein m is 2. In another preferred embodiment, the compound has the structure of a formula described herein, such as formula 1, 2a, 2b, 2c or 2d, wherein one of R * or R ** is phenyl substituted with 1 to 5 substituents each of which is independently selected from alkyl (greater than? d), aryl, substituted aryl, benzyl, substituted benzyl, (where k = 1, 2 or 3), CH2NH2, CH2NH-alkyl, CH2N (alkyl) 2, C02H, C02alkyl, COHN2, CONHalkyl, CON ( alkyl) 2, OH, alkoxy (greater than C6) aryloxy, SH, S-alkyl, S-aryl, S02alkyl, S03H, SCF3, CN, N02, NH2, 2 ° -amino, 3 ° -amino, NH2S02, OCH2CH2NH2, 0CH2CH2NHalkyl, OCH2CH2N (alkyl) 2, oxazolidin-2-yl, and oxazolidin-2-yl substituted with alkyl. - In a further preferred embodiment thereof, the phenyl has the structure 4 wherein R 4, R 5, R 6, R 7 and R 8 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl-aryl, substituted aryl, aralkyl, substituted aralkyl, (CH 2) k 0 H (where k = 1, 2 or 3 ), CH2NH2, CH2NH-alkyl, CH2N (alkyl) 2, C02H, C02alkyl, CONH2, CONHalkyl, CON (alkyl) 2, OH, alkoxy, aryloxy, SH, S-alkyl, S-aryl, S02alkyl, S02N (alkyl) 2, S02NHalkyl, S02NH2, S03H, SCF3, CN, halogen, CF3, N02, NH2, 2 ° -amino, 3 ° -amino, NH2S02, OCH2CH2NH2, OCH2CH2NHalkyl, OCH2CH2N (alkyl) 2, oxazolidin-2-yl, or oxazolidin-2-yl substituted with alkyl. A highly preferred embodiment is a compound of a formula described herein, such as formula 1, 2a, 2b, 2c or 2d, wherein R * is 3-fluorophenyl, R ** is 4-chlorophenyl, R9 is H, R11 is H, Az is CH, D is CH, J is CH and it can be called (3- (4,4-dimethyloxazolidin-2-yl) phenyl) borinic acid 8-hydroxyquinoline ester. Another embodiment described is a compound of a formula described herein, such as formula 1, 2a, 2b, 2c or 2d, wherein R * and R ** are each 3- (4,4-dimethyloxazolidin-2-yl) ) phenyl, R9 is H, R11 is H, Az is CH, D is CH, J is CH and can be called bis (3- (, 4-dimethyloxazolidin-2-yl) boric acid 8-hydroxyquinoline ester. preferred additional embodiment is a compound of a formula described herein, such as formula 1, 2a, 2b, 2c or 2d, wherein R * is 3-fluorophenyl, R ** is cyclopropyl, R9 is H, R11 is H, Az is CH, D is CH, J is CH and is referred to as (3-fluorophenyl) (cyclopropyl) borinic acid 8-hydroxyquinoline ester A highly preferred embodiment is a compound of a formula described herein, such as formula 1, 2a, 2b, 2c or 2d, wherein R * is 4- (N, N-dimethyl) -aminomethylphenyl, R ** is 4-cyanophenyl, R9 is H, R11 is H, A2 is CH, D is CH , J is CH and is referred to as (4 - (, N-dimet i 1) -aminome t i 1 f eni 1) (4-cyanophenyl) borinic acid ester of 8-hydroxyquinoline. Another highly preferred embodiment is a compound of a formula described herein, such as formula 1, 2a, 2b, 2c, or 2d, wherein R * is the same as R ** which is 3-c 1 or o- 4 -me ti 1 f in i 1 o, R9 is H, R11 is H, Az is CH, D is CH and E is OH, m = 0, r is 1, G is = 0 (double bond oxygen) and refers to bis (3-chloro-4-methylphenyl) borinic acid 3-hydroxy-piolinate ester. A highly preferred additional embodiment is a compound of a formula described herein, such as formula 1, 2a, 2b, 2c, or 2d, wherein R * is the same as R ** which is 2-methyl-4-chlorophenyl , R9 is H, R11 is H, A2 is CH, D is CH and E is OH, m = 0, r is 1, G is = 0 (double bond oxygen) and is referred to as 3-hydroxypicolinate ester of acid bis (2-methyl-4-chlorophenyl) borinic acid. In a preferred embodiment of a formula described herein, such as formula 1, 2a, 2b, 2c or 2d, R * and / or R ** are the same or are different, preferably wherein one of R * and R ** is a substituted or unsubstituted benzyl or R * and R ** are each a substituted or unsubstituted benzyl. In a additional preferred embodiment thereof, benzyl has the structure 5 wherein R 4, R 5, R 6, R 7 and R 8 are each independently selected from the group consisting of alkyl, cycloalkyl, aryl, substituted aryl, aralkyl, substituted aralkyl, (CH 2) kOH (where k = 1, 2 or 3), CH2NH2, CH2NH-alkyl, CH2N (alkyl) 2, C02H, C02alkyl, COHN2, CONHalkyl, CON (alkyl) 2, OH, alkoxy, aryloxy, SH, S-alkyl, S-aryl, S02alkyl, S02N (alkyl) 2, S02NHalkyl, S02NH2, S03H, SCF3, CN, halogen, CF3, N02, NH2, 2 ° -amino, 3 ° -amino, NH2S02, 0CH2CH2NH2-, OCH2CH2NHalkyl, OCH2CH2N (alkyl) 2, oxazolidin-2-yl, or oxazolidin-2-yl substituted with alkyl. A preferred embodiment is a compound of a formula described herein, such as formula 1, 2a, 2b, 2c, or 2d, R * and / or R ** are the same or are different, preferably wherein one of R * and R ** is a substituted or unsubstituted heterocycle or R * and R ** are each a substituted or unsubstituted heterocycle. In a further preferred embodiment thereof, the heterocycle has structure 6. wherein X = CH = CH, N = CH, NRiJ (where R = H, alkyl, aryl or aralkyl), 0, or S and wherein Y = CH or N, R1, R2 and R3 are each independently selected of the group consisting of hydrogen, alkyl, cycloalkyl, aryl, substituted aryl, aralkyl, substituted aralkyl, (CH2) kOH (wherein k = 1, 2 or 3), CH2NH2, CH2NH-alkyl, CH2N (alkyl) 2, C02H , C02alkyl, C0NH2, S-alkyl, S-aryl, S02alkyl, S02N (alkyl) 2, S02NHalkyl, S02NH2, S03H, SCF3, CN, halogen, CF3, N02, oxazolidin-2-yl, or substituted oxazolidin-2-yl with alkyl. A highly preferred embodiment is a compound of a formula described herein, such as formula 1, 2a, 2b, 2c or 2d, wherein R * is pyrid-3-yl, R ** is 4-chlorophenyl, R9 is H , R11 is H, Az is CH, D is CH, and J is CH (called 8-hydroxyquinoline ester of (pyridin-3-yl) (4-chlorophenyl) borinic acid). A highly preferred embodiment is a compound of a formula described herein, such as formula 1, 2a, 2b, 2c or 2d, wherein R * is 5-cyanopyrid-3-yl, R ** is vinyl, R9 is H , R11 is H, A2 is CH, D is CH, and J is CH (called 8-hydroxyquinoline ester of the acid (5-cyanopyrid-3- il) (vinyl) borinic). A preferred embodiment is a compound of a formula described herein, such as formula 1, 2a, 2b, 2c or 2d, wherein R9 is H, R11 is H, Az is CH, D is CH, and J is CH. Another preferred embodiment is a compound of a formula described herein, such as formula 1, 2a, 2b, 2c or 2d, wherein R9 is H, R11 is H, Az is CH, D is CH and E is OH, m = 0, r is 1, and G is = 0 (double bond oxygen). The structures of the invention also allow interactions of solvents that can give structures (such as Formulas Ib and 2e). which include atoms derived from the solvent found by the compounds of the invention during synthesis procedures and therapeutic uses. In this way, these solvent structures can themselves insinuate at least one of the compounds of the invention, especially between the boron and nitrogen atoms, themselves, in order to increase the ring size of these compounds by one or two atoms. For example, where the boron ring of a structure of the invention comprises 5 atoms, including, for example, boron, a nitrogen, an en and 2 carbons, the insinuation of a solvent atom between boron and nitrogen would give a ring of 7 members In one example, the use of hydr and amino solvents can give structures containing an en or nitrogen between the boron and ring nitrogen atoms to increase the size of the ring. These structures are expressly contemplated by the present invention, preferably where R *** is H or alkyl. Methods for making the compounds The synthesis of the compounds of the invention is achieved in various formats. Reaction scheme A demonstrates the synthesis of the intermediate borinic acids, and their subsequent conversion to the desired borinic acid complexes. When R * and R ** are identical, the reaction of two equivalents of an arylmagnesium halide (or aryllithium) with trialkyl borate, followed by acid hydrolysis yields the desired borinic acid. When R * and R ** are not identical, the reaction of an equivalent of an arylmagnesium halide (or aryllithium) with appropriate aryl (dialk borane (4), heteroaryl (dialk borane or alkyl (dialk borane (alkgroup) comprised of a portion of meth eth isoprop or prop, followed by acid hydrolysis gives the unsymmetrical borinic acids 6 in excellent yields. Where is Applicable, the reaction of the alkylene esters (3, T = none, CH2, C (CH3) 2) with the organocerium, organolithium, organomagnesium or appropriate equivalent reagent is convenient. As shown in Reaction Scheme A, borinic acid complexes are obtained from the boric acid precursor by reaction with one equivalent of the desired heterocyclic ligand in suitable solvents (ie, ethanol, isopropanol, dioxane, ether, toluene, dimethylformamide, N-methylpyrrolidone, or tetrahydrofuran). Scheme of reaction? certain situations, the compounds invention may contain one or more asymmetric carbon atoms, so that the compounds may exist in different stereoisomeric forms. These compounds can be, for example, racemates or optically active forms. In these situations, the individual enantiomers, that is, optically active forms, can be obtained by asymmetric synthesis or by resolution of the racemates. The resolution of the racemates can be achieved, for example, by conventional methods such as crystallization in the presence of a resolving agent, or chromatography, using, for example, a chiral HPLC column. I. b.) Boronic Esters In a first aspect, the invention provides a compound having a structure according to Formula I: (I) wherein B is boron, Rla is a member selected from a negative charge, a salt counterion, H, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted aryl or unsubstituted, and substituted or unsubstituted heteroaryl. M is a selected member of en, sulfur and NR2a. R2a is a member selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. J is a member selected from (CR3aRa) nl and CR5a, R3a, Ra, and R5a are members independently selected from H, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. The index ni is an integer selected from 0 to 2. W is a member selected from C-0 (carbonyl), (CR6aR7a) mi and CR8a, R6a, R7a and R8a are members independently selected from H, cyano, substituted alkyl or unsubstituted, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. The index mi is a selected member of 0 and 1. A is a selected member of CR9a and N. D is a selected member of CR10a and N. E is a selected member of CRlla and N. G is a selected member of CR12a and N. R9a, R10a, Rlla and R12a are members independently selected from H, OR * a, NR * aR ** a, SR * a -S (0) R * a, -S (0) 2R * a, -S (0) 2NR * a R ** a, -C (0) R * a, -C (0) OR * a, -C (0) NR * to R ** a, nitro, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted aryl or unsubstituted, and substituted or unsubstituted heteroaryl. Each R * a and R ** a are independently selected members of H, nitro, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted heteroaryl or unsubstituted The combination of integers (A + D + E + G) is an integer selected from 0 to 3. A member selected from R3a, R4a and R5a and a selected member of R6a, R7a and R8a, together with the atoms at which are attached, optionally join to form a ring of 4 to 7 members. R3a and R4a, together with the atoms to which they are attached, optionally join to form a 4- to 7-membered ring. R6a and R7a, together with the atoms to which they are attached, optionally join to form a 4- to 7-membered ring. R9a and R10a, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring. R10a and Rlla, together with the atoms to which they are attached, optionally join to form a 4- to 7-membered ring. Rlla and R12a, together with the atoms at which join, optionally join to form a ring of 4 to 7 members. In an exemplary embodiment, the compound has a structure according to Formula (la): In another exemplary embodiment, each R3a and R4a is a member independently selected from H, cyano, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, trifluoromethyl, substituted or unsubstituted hydroxymethyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted benzyl, substituted phenyl or unsubstituted, substituted or unsubstituted mercaptomethyl, substituted or unsubstituted mercaptoalkyl, substituted or unsubstituted aminomethyl, substituted or unsubstituted alkylaminomethyl, substituted or unsubstituted dialkylaminomethyl, substituted or unsubstituted arylaminomethyl, substituted or unsubstituted indolyl and substituted or unsubstituted amido. In another exemplary embodiment, each R3a and R4a is a member independently selected from cyano, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, trifluoromethyl, hydroxymethyl substituted or unsubstituted, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted benzyl, substituted or unsubstituted phenyl, substituted or unsubstituted mercaptomethyl, substituted or unsubstituted mercaptoalkyl, substituted or unsubstituted aminomethyl, substituted or unsubstituted alkylaminomethyl, substituted or unsubstituted dialkylaminomethyl, substituted or unsubstituted arylaminomethyl, indolyl substituted or unsubstituted, substituted or unsubstituted amido. In another exemplary embodiment, each R3a and R4a is a member selected from H, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, substituted or unsubstituted propyl, substituted or unsubstituted isopropyl, substituted or unsubstituted butyl, substituted or unsubstituted t-butyl, phenyl substituted or unsubstituted and substituted or unsubstituted benzyl. In another exemplary embodiment, R3a and R4a is a member selected from methyl, ethyl, propyl, isopropyl, butyl, t-butyl, phenyl and benzyl. In another example embodiment, R3a is H and R4a is a member selected from methyl, ethyl, propyl, isopropyl, butyl, t-butyl, phenyl and benzyl. In another example embodiment, R3a is H and R4a is H. In another example embodiment, each R9a, R10a, Rlla and R12a is a member independently selected from H, OR * a, NR * R ** a, SR * a , -S (0) R * a, -S (0) 2R * a, -S (0) 2NR * a R ** a, -C (0) R * a, -C (0) OR * a, -C (0) NR ** to R ** a, halogen, cyano, nitro, methoxy replaced or unsubstituted, substituted or unsubstituted methyl, substituted or unsubstituted ethoxy, substituted or unsubstituted ethyl, trifluoromethyl, substituted or unsubstituted hydroxiraethyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted benzyl, substituted or unsubstituted phenyl, substituted or unsubstituted phenyloxy, substituted or unsubstituted phenylmethoxy, substituted triphenyloxy or unsubstituted, substituted or unsubstituted pyridinyloxy, substituted or unsubstituted pyrimidinyloxy, substituted or unsubstituted benzylfurane, substituted or unsubstituted methylthio, substituted or unsubstituted mercaptomethyl, substituted or unsubstituted mercaptoalkyl, substituted or unsubstituted phenylthio, substituted or unsubstituted thiophenylthio, substituted or unsubstituted phenyl-methylthio, substituted or unsubstituted pyridinylthio, substituted or unsubstituted pyrimidinylthio, substituted or unsubstituted benzylthiofuranyl, substituted or unsubstituted phenylsulfonyl, substituted or unsubstituted benzylsulfonyl, substituted or unsubstituted phenylmethylsulfonyl I, substituted or unsubstituted thiophenylsulfonyl, substituted or unsubstituted pyridinylsulfonyl, substituted or unsubstituted pyrimidinylsulfonyl, substituted or unsubstituted sulfonamidyl, substituted or unsubstituted phenylsulfinyl, substituted or unsubstituted benzylsulfinyl, substituted or unsubstituted phenylmethylsulfonyl, substituted or unsubstituted thiophenylsulfinyl, substituted or unsubstituted pyridinylsulfinyl, substituted or unsubstituted pyrimidinylsulfinyl, substituted or unsubstituted amino, substituted or unsubstituted alkylamino substituted or unsubstituted dialkylamino, substituted or unsubstituted trifluoromethylamino, substituted or unsubstituted aminomethyl, substituted or unsubstituted alkylaminomethyl, substituted or unsubstituted dialkylaminomethyl, substituted or unsubstituted arylaminomethyl, benzylamino substituted or unsubstituted, substituted or unsubstituted phenylamino, substituted or unsubstituted thiophenylamino, substituted or unsubstituted pyridinylamino, substituted or unsubstituted pyrimidinylamino, substituted or unsubstituted indolyl, substituted or unsubstituted morpholino, substituted or unsubstituted alkylamino, substituted or unsubstituted arylamido, substituted or unsubstituted ureido, carbamoyl substituted or unsubstituted, and substituted or unsubstituted piperizinyl. In an example embodiment, R9a, R10a, Rlla and R12a are selected from the previous list in substituents with the exception of -C (0) R * a, -C (0) OR * a, -C (0) NR * to R ** a. In another example embodiment R9a, R10a, Rlla and R12a are members independently selected from fluoro, chloro, bromo, nitro, cyano, amino, methyl, hydroxylmethyl, trifluromethyl, methoxy, trifluoromethoxy, ethyl, diethylcarbamoyl, pyridin-2-yl, pyridin. -3-yl, pyridin-4-yl, pyrimidinyl, piperizino, piperazinyl, piperazinocarbonyl, piperizinylcarbonyl, carboxyl, 1-tetrazolyl, 1-ethoxycarbonylmethoxy, carboxymethoxy, thiophenyl, 3- (butylcarbonyl) phenylmethoxy, lH-tetrazol-5-yl, 1-ethoxycarbonylmethyloxy, 1-ethoxycarbonylmethyl-, 1-ethoxycarbonyl-, carboxymethoxy-, thiophene- 2-yl, thiophen-2-ylthio-, thiophen-3-yl, thiophen-3-ylthio, 4-fluorophenylthio, butylcarbonylphenylmethoxy, butylcarbonylphenylmethyl, butylcarbonylmethyl, 1- (piperidin-1-yl) carbonyl) methyl, 1- (piperidine -l-yl) carbonyl) methoxy, 1- (piperidin-2-yl) carbonyl) methoxy, 1- (piperidin-3-yl) carbonyl) methoxy), 1- (4 - (pyrimidin-2-yl) piperazine- 1-yl) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methyl, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl, 1-4- (Pyrimidin-2-yl) piperazin-1-yl, 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl), 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonylmethyl, (1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl) methoxy), 1- (4- (pyridin-2-yl) piperazin-1-yl, lH-indol-l-yl, morpholino-, morfo linyl, morpholinocarbonyl, morpholinylcarbonyl, phenylureido, phenylcarbamoyl, acetamido, 3- (phenylthio) -lH-indol-1-yl, 3- (2-cyanoethylthio) -lH-indol-1-yl, benzylamino, 5-methoxy-3 (phenylthio) -1H-indol-1-yl, 5-methoxy-3- (2-cyanoethylthio) -lH-indol-1-yl)), 5-chloro-lH-indol-1-yl, 5-chloro- 3- (2-cyanoethylthio) -lH-indol-1-yl)), dibenzylamino, benzylamino, 5-chloro-3- (phenylthio) -lH-indol-1-yl), 4- (1H-tetrazol-5) -yl) phenoxy, 4- (lH-tetrazol-5-yl) phenyl, 4- (lH-tetrazol-5-yl) phenylthio, 2-cyanophenoxy, 3-cyano-phenoxy, 4-cyano-phenoxy, 2-cyanophenylthio, 3- cyanophenylthio, 4-cyanophenylthio, 2-chlorophenoxy, 3-chlorophenoxy, 4-chlorophenoxy, 2-fluorophenoxy, 3-fluorophenoxy, 4-fluorophenoxy, 2-cyanobenzyloxy, 3-cyanobenzyloxy, 4-cyanobenzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 2-fluorobenzyloxy, 3-fluorobenzyloxy, 4-fluorobenzyloxy, unsubstituted phenyl, unsubstituted benzyl. In an exemplary embodiment, R9a is H and R12a is H. In an exemplary embodiment, the compound according to Formula (I) or Formula (la) is a member selected from: In an exemplary embodiment, the compound has a structure according to one of Formulas I-Io with selections of substituents for R9a, R10a, Rlla and R12a including all possibilities contained in paragraph 90 (of the English text) except by H. In an exemplary embodiment, the compound has a structure according to one of Formulas Ib-Io with selections of substituents for R9a, R10a, Rlla and R12a including all possibilities contained in paragraph 91 (from the English text) ) except for H. In an example mode, the compound has a formula according to Formulas (Ib) - (le) wherein Rla is a selected member of H, a negative charge and a salt counterion and the remaining R group (R9a in Ib, R10a in Ic, Rll in Id, and R12a in Ic) is a member selected from fluoro, chloro, bromo, nitro, cyano, amino, methyl, hydroxylmethyl, trifluromethyl, methoxy, trifluoromethoxy, ethyl, diethylcarbamoyl, pyridin-2-yl, pyridin-3- ilo, pyridin-4-yl, pyrimidinyl, piperizino, piperazinyl, piperazinocarbonyl, piperizinylcarbonyl, carboxyl, 1-tetrazolyl, 1-ethoxycarbonylmethoxy, carboxymethoxy, thiophenyl, 3- (butylcarbonyl) phenylmethoxy, lH-tetrazol-5-yl, 1- ethoxycarbonylmethyloxy, 1-ethoxycarbonylmethyl-, 1-ethoxycarbonyl-, carboxymethoxy-, thiophen-2-yl, thiophen-2-ylthio-, thiophen-3-yl, thiophen-3-ylthio, 4-fluorophenylthio, butylcarbonylphenylmethoxy, butylcarbonylphenylmethyl, butylcarbonylmethyl, 1- (piperidin-1-yl) carbonyl) methyl, 1- (piperidin-1-yl) carbonyl) methoxy, 1- (piperidin-2-yl) carbonyl) methoxy, 1- (piperidin-3-yl) carbonyl) methoxy), 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methyl, 1- ( 4- (Pyrimidin-2-yl) piperazin-1-yl) carbonyl, 1-4- (pyrimidin-2-yl) piperazin-1-yl, 1- (4- (pyridin-2-yl) piperazin-1- il) carbonyl), 1- (4- (pyridin-2-yl) piperazin-1-y1) carbonylmethyl, (1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl) methoxy), - (4- (pyridin-2-yl) piperazin-1-yl, lH-indol-1-yl, morpholino-, morpholinyl, morpholinocarbonyl, morpholinylcarbonyl, phenylureido, phenylcarbamoyl, acetamido, 3- (phenylthio) -lH-indole- l -yl, 3- (2-cyanoethylthio) -lH-indole- l -yl, benzylamino, 5-methoxy-3- (phenylthio) -lH-indol-1-yl, 5-methoxy-3- (2-cyanoethylthio) -1H-indol-1-yl), 5-chloro- lH-indol-l-yl, 5-chloro-3- (2-cyanoethylthio) -lH-indol-l-yl)), dibenzylamino, benzylamino, 5-chloro-3- (phenylthio) -lH-indole-l- ilo)), 4- (lH-tetrazol-5-yl) phenoxy, 4- (lH-tetrazol-5-yl) phenyl, 4- (lH-tetrazol-5-yl) phenylthio, 2-cyanophenoxy, 3-cyanophenoxy , 4-cyanophenoxy, 2-cyanophenylthio, 3-cyanophenylthio, 4-cyanophenylthio, 2-chlorophenoxy, 3-chlorophenoxy, 4-chlorophenoxy, 2-fluorophenoxy, 3- fluorophenoxy, 4-fluorophenoxy, 2-cyanobenzyloxy, 3-cyanobenzyloxy, 4-cyanobenzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 2-fluorobenzyloxy, 3-fluorobenzyloxy, and 4-fluorobenzyloxy. In an exemplary embodiment, the compound has a formula according to the Formulas (If) - (Ik) wherein Rla is a selected member of H, a negative charge and a salt counterion and each of the two remaining R groups (R9a and R10a in If, R9a and Rlla in Ig, R9a and R12a in Ih, R10a and Rlla in Ii, R10a and R12a in Ij, Rlla and R12a in Ik) is a member independently selected from fluoro, chloro, bromo, nitro , cyano, amino, methyl, hydroxymethyl, trifluoromethyl, methoxy, trifluoromethoxy, ethyl, diethylcarbamoyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidinyl, piperizino, piperazinyl, piperazinocarbonyl, piperizinylcarbonyl, carboxyl, -tetrazolyl, 1-ethoxycarbonylmethoxy, carboxymethoxy, thiophenyl, 3- (butylcarbonyl) phenylmethoxy, 1H-tetrazol-5-yl, 1-ethoxycarbonylmethyloxy, 1-ethoxycarbonylmethyl-, 1-ethoxycarbonyl-, carboxymethoxy-, thiophen-2-yl, thiophen -2-ilthio-, thiophen-3-yl, thiophen-3-ylthio, 4-fluorophenylthio, butylcarbonylphenylmethoxy, butylcarbonylphenylmethyl, butylcarb onylmethyl, 1- (piperidin-1-yl) carbonyl) methyl,. 1- (piperidin-1-yl) carbonyl) methoxy, 1- (piperidin-2-yl) carbonyl) methoxy, 1- (piperidin-3-yl) carbonyl) methoxy), 1- (4- (pyrimidine-2- il) piperazin-1-yl) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methyl, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl, 1-4- (pyrimidin-2-yl) piperazine- 1-yl, 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl), 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonylmethyl, (1- (4 - (pyridin-2-yl) piperazin-1-yl) carbonyl) methoxy), 1- (4- (pyridin-2-yl) piperazin-1-yl, 1 H -indol-1-yl, morpholino-, morpholinyl, morpholinocarbonyl, morpholinylcarbonyl, phenylureido, phenylcarbamoyl, acetamido, 3- (phenylthio) -lH-indol-1-yl, 3- (2-cyanoethylthio) -lH-indol-1-yl, benzylamino, 5-methoxy-3- (phenyl) ) -lH-indol-l-yl, 5-methoxy-3- (2-cyanoethylthio) -lH-indol-l-yl), 5-chloro-lH-indol-1-yl, 5-chloro-3- (2-cyanoethylthio) -lH-indol-1-yl)), dibenzylamino, benzylamino, 5-chloro-3- (phenylthio) -lH-indol-1-yl), 4- (lH-tetrazol-5-yl) ) phenoxy, 4- (lH-tetrazol-5-yl) phenyl, 4- (lH-tetrazol-5-yl) phenylthio, 2-cyanophenoxy, 3-cyanophenoxy, 4-cyanophenoxy, 2-cyanophenylthio, 3-cyanophenylthio, 4 -cyanophenylthio, 2-chlorophenoxy , 3-chlorophenoxy, 4-chlorophenoxy, 2-fluorophenoxy, 3-fluorophenoxy, 4-fluorophenoxy, 2-cyanobenzyloxy, 3-cyanobenzyloxy, 4-cyanobenzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 2-fluorobenzyloxy, 3 -fluorobenzyloxy, and 4-fluorobenzyloxy. In an exemplary embodiment, the compound has a formula according to formulas (II) - (lo) wherein Rla is a selected member of H, a negative charge and a salt counterion and each of the three remaining R groups (R9a, R10a, R11 in (II), R9a, R10a, R12a in (Im), R9a, Rlla, R12a in (In), R10a, Rlla, R12a in (lo)) is a member independently selected from fluoro, chloro, bromo, nitro, cyano , amino, methyl, hydroxymethyl, trifluoromethyl, methoxy, trifluoromethoxy, ethyl, diethylcarbamoyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidinyl, piperizino, piperazinyl, piperazinocarbonyl, piperizinylcarbonyl, carboxyl, 1-tetrazolyl , 1-ethoxycarbonylmethoxy, carboxymethoxy, thiophenyl, 3- (butylcarbonyl) phenylmethoxy, 1H-tetrazol-5-yl, 1-ethoxycarbonylmethyloxy, 1-ethoxycarbonylmethyl-, 1-ethoxycarbonyl-, carboxymethoxy-, thiophen-2-yl, thiophen-2 -thio-, thiophen-3-yl, thiophen-3-ylthio, 4-fluorophenylthio, butylcarbonylphenylmethoxy, butylcarbonylphenylmethyl, butylcarbonylmethyl, 1- (piperidin-1-yl) carbonyl) methyl, 1- (piperidin-1-yl) carbonyl) methoxy, 1- (piperidin-2-yl) carbonyl) methoxy, 1- (piperidin-3-yl) carbonyl) methoxy), 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methoxy , 1- (4- (pyrimidin-2-yl ) piperazin-1-yl) carbonyl) methyl, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl, 1-4- (pyrimidin-2-yl) piperazin-1-yl, 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl), 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonylmethyl, (1- (4- (pyridin-2- il) piperazin-1-yl) carbonyl) methoxy), 1- (4- (pyridin-2-yl) piperazin-1-yl, 1H-indol-1-yl, morpholino-, morpholinyl, morpholinocarbonyl, morpholinylcarbonyl, phenylureido, phenylcarbamoyl, acetamido, 3- (phenylthio) -lH-indol-1-yl, 3- (2-cyanoethylthio) -lH-indol-1-yl, benzylamino, 5-methoxy-3- (phenylthio) -lH-indol-1-yl, 5-methoxy-3- (2-cyanoethylthio) -lH-indol-1-yl), 5-chloro-1H-indol-1-yl, 5-chloro-3- (2-cyanoethylthio) -lH-indole l-yl)), dibenzylamino, benzylamino, 5-chloro-3- (phenylthio) -lH-indol-1-yl), 4- (lH-tetrazol-5-yl) phenoxy, 4- (lH-tetrazol- 5-yl) phenyl, 4- (lH-tetrazol-5-yl) phenylthio, 2-cyanophenoxy, 3-cyanophenoxy, 4-cyanophenoxy, 2-cyanophenylthio, 3-cyanophenylthio, 4-cyanophenylthio, 2-chlorophenoxy, 3-chlorophenoxy, 4-chlorophenoxy, 2 Fluorophenoxy, 3-fluorophenoxy, 4-fluorophenoxy, 2-cyanobenzyloxy, 3-cyanobenzyloxy, 4-cyanobenzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 2-fluorobenzyloxy, 3-fluorobenzyloxy, and 4-fluorobenzyloxy. In another example embodiment, there is a condition that the compound can not be a selected member of Cl-C40. In another example embodiment, there is a condition that the compound can not have a structure according to the formula (Ix): wherein R is a member selected from H, methyl, ethyl and phenyl. R10b is a member selected from H, OH, NH2, SH, halogen, substituted or unsubstituted phenoxy, unsubstituted or substituted phenylalkyloxy, substituted or unsubstituted phenylthio and substituted or unsubstituted phenylalkylthio. Rllb is a member selected from H, OH, NH2, SH, methyl, substituted or unsubstituted phenoxy, substituted or unsubstituted phenylalkyloxy, substituted or unsubstituted phenylthio, and substituted or unsubstituted phenylalkylthio. In another example embodiment, there is a condition that the compound can not have a structure according to the formula (Ix) wherein Rlb is a member selected from a negative charge, H and a salt counterion. In another example embodiment, there is a condition, that the compound can not have a structure according to the formula (Ix) wherein Rlb and Rllb are H. In another example embodiment, there is a condition that the compound can not have a structure according to formula (Ix) wherein one member selected from R10b and Rllb is an H and another member selected from R10b and Rllb is a member selected from halo, methyl, cyano, ethoxy, hydroxymethyl and p-cyanophenyloxy. In another exemplary embodiment, there is a condition that the compound can not have a structure according to formula (Ix) wherein R10b and Rllb are independently selected members of fluoro, chloro, methyl, cyano, methoxy, hydroxymethyl, and p- cyanophenyl. In another example embodiment, there is a condition that the compound can not have a structure according to the formula (Ix) wherein Rlb is a selected member of a negative charge, H and salt counter ion; R7b is H; R10b is F and RUb is H. In another exemplary embodiment, there is a condition that the compound can not have a structure according to Formula (Ix) wherein Rllb and R12b, together with the atoms to which they are attached, are join to form a phenyl group. In another exemplary embodiment, there is a condition that the compound can not have a structure according to Formula (Ix) wherein Rlb is a selected member of a negative charge, H and a salt counterion; R7b is H; R10b is 4-cyanophenoxy; and Rllb is H. In another example embodiment, there is a condition that the compound can not obtain a structure according to Formula (Iy) wherein R10b is a member selected from H, halogen, CN and Ci-4alkyl substituted or unsubstituted. In another example embodiment, there is a condition that a structure does not have what is a selected member of the Formulas (I) to (lo) at least one selected member of R3a, R4a, R5a, R6a, R7a, R8a, R9a, R10a, Rlla and R12a is nitro, cyano or halogen. In another example embodiment, there is a condition that when M is oxygen, W is a member selected from (CR3aR4a) ni, where neither is 0, J is a member selected from (CR6aR7a) mi, where mi is 1, A is CR9a, D is CR10a, E is CRll, G is CR12a, R9a is non-halogen, methyl ethyl or is optionally linked with R10a to form a phenyl ring; R10a is not substituted phenoxy, C (CH3) 3, halogen, CF3, methoxy, ethoxy, or is optionally linked with R9a to form a phenyl ring; Rlla is not halogen or is optionally linked with R10a to form a phenyl ring; R12a is not halogen. In another example embodiment, there is a condition when M is oxygen, W is a member selected from (CR3aRa) ni, where neither is 0, J is a member selected from (CR6aR7a) mi where mi is 1, A is CR9a , D is CR10a, E is CRlla, Gl is CR12a, then neither R6a nor R7a are halophenyl. In another example embodiment, there is a condition when it is oxygen, W is a member selected from (CR3aRa) ni, where neither is 0, J is a member selected from (CRaR7a) mi, where mi is 1, A is CR9a , D is CR10a, E is CRlla, G is CR12a, and R9a, R10a and Rlla are H, then R6a, R7a and R12a are not H. In another example embodiment, there is a condition that when M is oxygen, where neither is 1, J is a member selected from (CR6aR7a) mi, where mi is 0, A is CR9a, D is CR10a, E is CRlla, G is CR12a, R9a is H, R10a is H, Rlla is H, R6a is H, R7a is H, R12a is H, R12a is H, then W is not C = 0 (carbonyl). In another form of example, there is a condition that when M is oxygen, W is CRa, J is CR8a, A is CR9a, D is CR10a, E is CRlla, G is CR12a, R6a, R7a, R9a, R10a, Rlla and R12a are H, then R5 and R8a, together with the atoms to which they are attached, do not form a phenyl ring. In an exemplary embodiment, the compound of the invention has a structure that is a member selected from: in which q is a member between 0 and 1. Rg is halogen, Ra, Rb, Rc, Rd and Re are members independently selected from a selected member of H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl , substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. In an example embodiment, there is a condition that the compound is not a selected member of In an exemplary embodiment, the compound has a structure that is a member selected from: (Iaj) and (Iak).

In an exemplary embodiment, Ra, Rd and Rc are each members independently selected from: In an example embodiment, Rb and Rc are members independently selected from H, methyl, In another example mode selected member of H, methyl, '' '' and. In another exemplary embodiment, Rb and Rc are, together with the nitrogen to which they are attached, optionally linked to form a selected member of In an example mode, Ra is a selected member of In an example mode, Rd is a selected member of In an example mode, Re is a selected member of ?? 73 In an exemplary embodiment, the compound has a structure that is described in tables 2A-2J. In an exemplary embodiment, the compound has a structure that is described in tables 3A-3H. In an exemplary embodiment, the compound has structure according to a selected member of formula 1 (b), 1 (c), 1 (d) and 1 (c) wherein the remaining group R (R9a for 1 (b) ), R10a for 1 (c), Rlla for 1 (d) and R12a for 1 (e)) is carboxymethoxy. In an exemplary embodiment, the compound has a structure that is a member selected from the Formulas (If) - (Ik), wherein either R9a or R10a for the Formula (If), either R9a or Rlla for the Formula ( Ig), either R9a or R12a for Formula (Ih), either R10a or Rlla for Formula (Ii), either Rioa or Ri2a for Formula (ij), either Rlla or R12a for the Formula (Ik) is halogen, and the other substituent is pairing (example if Ra is G in the Formula (If), then R10a is selected from the following list of substituents), is a member selected from NH2, N (CH3H) H , and N (CH3) 2. In another example embodiment, the compound has structure that is a member selected from: wherein R * and R ** are members selected from: H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. In an exemplary embodiment, the compound is a member selected from where Rla is a selected member of a negative charge, H and a counterion salt. In another example embodiment, the compound has a structure that is a member selected from: (Iak), where q is 1 and R is a selected member of fluoro, chlorine and bromine. In another exemplary embodiment, the compounds and embodiments described above in Formulas (I) - (Io) can form a hydrate with water, a solvate with an alcohol (eg, methanol, ethanol, propanol); an adduct with an amino compound (for example, ammonia, methylamine, ethylamine); an adduct with an acid (for example, formic acid, acetic acid); complexes with ethanolamine, quinoline, amino acids, and the like. In another example embodiment, the compound has a structure according to Formula (Ip): wherein Rx2 is a member selected from a substituted or unsubstituted Ci-Csalkyl and substituted or unsubstituted Ci-Csheteroalkyl. Ry2 and Rz2 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. ** A1-M1 are not defined. In another example embodiment, the compound has a structure according to Formula (Iq): where B is boron. Rx2 is a member selected from Ci-C5 substituted or unsubstituted alkyl and Ci-Csheteroalkyl substituted or unsubstituted Ry2 and Rz2 are independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. In another exemplary embodiment, at least one member selected from R3a, R4a, R5a, R6a, R7a, R8a, R9a, R10a, Rlla and R12a is a member selected from nitro, cyano and halogen. In another example embodiment, the compound has a structure that is a member selected from the following Formulas: In another example embodiment, the compound has a formula according to Formulas (Ib) - (le) wherein at least one member selected from R3a, R4a, R5a, R6a, R7a, R8a, R9a, R10a, Rlla and R12a is a selected member of nitro, cyano, fluoro, chlorine, bromine and cyanophenoxy. In another example embodiment, the compound is a member selected from In another example embodiment, the member compound selected from In another example embodiment, there is a condition that the compound can not obtain a structure according to Formula (Iaa): wherein R6b, R9b, R10b, Rllb and R12b have the same list of substituents as described for Formulas (Ix) and (Iy) above. In another exemplary embodiment, the invention provides poly- or multi-valent species of the compounds of the invention. In an exemplary embodiment, the invention provides a dimer of the compounds described herein. In an exemplary embodiment, the invention provides a dimer of the compounds described herein. In an exemplary embodiment, the invention provides a dimer of a compound that is a member selected from C1-C96. In an example mode, the dimer is a selected member of In an exemplary embodiment, the invention provides an anhydride of the compounds described herein. In an exemplary embodiment, the invention provides an anhydride of the compounds described herein. In an exemplary embodiment, the invention provides an anhydride of a compound that is a member selected from C1-C96. In an exemplary embodiment, the anhydride is a member selected from In an exemplary embodiment, the invention provides a trimer of the compounds described herein. In an exemplary embodiment, the invention provides a trimer of the compounds described herein. In an exemplary embodiment, the invention provides a trimer of a compound that is a member selected from C1-C96. In an example embodiment, trimer is a member selected from where R15 is a selected member of CN, COOH and , R16 and R17 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. The index p is an integer selected from 1 to 5. The index z is an integer selected from 1 to 8. X is a selected member of S and 0. In another example embodiment, the compound has structure according to the Formula (VIII): wherein Ra is a selected member of substituted or unsubstituted aryl and substituted or unsubstituted arylalkyl. R10a is a member selected from H, halogen, substituted or unsubstituted aryl, substituted or unsubstituted aryloxy, substituted or unsubstituted arylalkoxy, substituted or unsubstituted arylthio and substituted or unsubstituted arylalkylthio. In another example embodiment, the compound has a structure that is a member selected from: In another example embodiment, the compound is In another aspect, the invention provides compounds useful in methods having a structure according to Formula IX: wherein the variables A, D, E and G are described in the other part of the present. R20, R21 and R22 are independently selected from a negative charge, a salt counterion, H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and heteroaryl replaced or unsubstituted. In another example embodiment, the compound has a structure according to the Formula In another example mode, it is a member selected from: The compounds of the invention can form a hydrate with water, solvates with alcohols such as methanol, ethanol, propanol and the like; adducts with amino compounds, such as ammonia, methylamine, ethylamine and the like; adducts with acids, such as formic acid, acetic acid and the like; complexes with ethanolamine, quinoline, amino acids and the like. In an exemplary embodiment, the compound has a structure that is a member selected from 5-chloro-l, 3-dihydro-lH-hydroxy-2, 1-benzoxazole (Cl), 1,3-Dihydro-1-hydroxy 2, 1-benzoxazole (C2), 5-Fluoro-l, 3-dihydro-l-hydroxy-3-methyl-2, 1-benzoxazole (C3), 6-Fluoro-l-hydroxy-l, 2, 3, 4-tetrahydro-2, 1-benzoxaborine (C4), 5, β-Dlifluoro-1, 3- dihydroxy-l-hydroxy-2, 1-benzoxazole (C5), 5-cyano-l, 3-dihydro-l-hydroxy-1,2-benzoxazole (C6), 1,3-Dihydro-l-hydroxy-5- methoxy-2, 1-benzoxazole (C7), 1,3-dihydro-l-hydroxy-5-methyl-2, 1-benzoxazole, (C8), 1,3-dihydro-l-hydroxy-5-hydroxymethyl-2 , 1-benzoxazole, (C9), 1,3-Dihydro-5-fluoro-G-hydroxy-2, 1-benzoxazole, (CIO) 1, 3-Dihydro-2-oxa-l cyclopenta [a] naphthalene (Cll) , 7-Hydroxy-2, 1-oxaborolane [5, 4 cjpyridine (C12) 1, 3-Dihydroxy-6-fluoro-l-hydroxy-2, 1 benzoxabole, (C13), 3-Benzyl-l, 3-dihydro -l-hydroxy-3-methyl-2, 1-benzoxazole (C14), 3-Benzyl-l, 3-dihydro-l-hydroxy-2, 1 benzoxabol (C15) 1,3-Dihydro-4-fluoro-hydroxy- 2, 1 benzoxazole, (C16), 5- (4-Cyanophenoxy) -1, 3-dihydro-l-hydroxy-2, 1-benzoxazole, (C17), 6- (4-cyano-phenoxy) -1, 3-dihydro- l hydroxy-2, 1-benzoxazole ((C18), 6- (3-Cyanophenoxy) -1, 3 dihydro-l-hydroxy-2, 1-benzoxazole (C19), 6- (4-chlorophenoxy) 1, 3 dihydro-l-hydroxy-2, 1-benzoxazole (C20), 6-phenoxy-l, 3 dihydro-l-hydroxy-2, 1-benzoxazole (C21), 5- (4-cyanobenzyloxy), 3-dihydro-l-hydroxy-2, 1-benzoxazole, (C22) 5- (2 Cyanophenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole (C23) 5 Phenoxy-1,3-dihydro-l-hydroxy-2, 1-benzoxazole (C24) 5- [4- (N, N-Diethylcarbamoyl) phenoxy] -1,3-dihydro-l-hydroxy-2, 1-benzoxazole (C25), 1,3-Dihydro-l-hydroxy-5- [4 (morpholinocarbonyl) phenoxy] -2, 1-benzoxazole, (C26) 5- (3,4-dicyanophenoxy) -1, 3-dihydro-l-hydroxy-2, 1-benzoxazole (C27) 6 Phenylthio-1,3-dihydro -hydroxy-2, 1-benzoxazole (C28) 6- (4 trifluoromethoxyphenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole (C29) 5- (M-methyl-N-phenylsulfonylamino) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole (C30) ), 6- (4-Methoxyphenylthio) -1,3-dihydro-hydroxy-2, 1-benzoxazole (C31), 6- (4-methoxyphenylthio) -1,3-dihydro-hydroxy-2, 1-benzoxazole (C32) ) 6- (4-Methoxyphenylthio) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole (C33), 6- (4-methoxyphenylsulfinyl) -1, 3-dihydro-l-hydroxy-2, 1- Benzoxazole (C34), 5-Trifluoromethyl-1,3-dihydro-hydroxy-2, 1-benzoxazole (C35), 4- (4-Cyanophenoxy) -1, 3-dihydro-hydroxy-2, 1-benzoxazole (C36) , 5- (3-Cyanophenoxy) -1,3-dihydro-hydroxy-2, 1-benzoxazole (C37), 5- (4-Carboxyphenoxy) -l-hydroxy-2, 1-benzoxazole (C38), l-Hydroxy -5- [4- (tetrazol-l-yl) phenoxy] -2, 1-benzoxazole (C39), 5-chloro-l, 3-dihydro-lH-hydroxy-2, 1-benzoxazole, 1,3-Dihydro l-hydroxy-2, 1-benzoxazole, 5-Fluoro-l, 3-dihydro-l-hydroxy-3-methyl-2, 1-benzoxazole, 6-Fluoro-l-hydroxy-l, 2,3, 4- tetrahydro-2, 1-benzoxazole, 5, 6-Difluoro-1,3-dihydroxy-l-hydroxy-2, 1-benzoxazole, 5-cyano-l, 3-dihydro-1-hydroxy-1,2-benzoxazole, 1,3-dihydro-1-hydroxy 5-methoxy-2, 1-benzoxazole, 1,3-Dihydro-l-hydroxy-5-methyl-2, 1-benzoxazole, 1,3-Dihydro-l-hydroxy-5-hydroxymethyl-2, 1-benzoxazole, 1,3-Dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole, 1,3-Dihydro-2-oxa-l-cyclopenta [?] Naphthalene 7-Hydroxy-2, 1-oxaborolane [5.4 -c] pyridine, 1,3-Dihydroxy-6-fluoro-l-hydroxy-2, 1-benzoxazole, 3-Benzyl-l, 3-dihydro-l-hydroxy-3-methyl-2, 1-benzoxazole, 3 -Benzyl-1, 3-dihydro-l-hydroxy-2, 1-benzoxabol, 1,3-Dihydro-4-fluoro-hydroxy-2, 1- benzoxabole, 5- (4-cyanophenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole, 6- (4-cyanophenoxy) -1, 3-dihydro-l-hydroxy-2, 1-benzoxazole, 6- (3-Cyanophenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole, 6- (chlorophenoxy) -1, 3-dihydro-l-hydroxy-2, 1-benzoxazole, 6-phenoxy -l, 3-dihydro-l-hydroxy-2, 1-benzoxazole, 5- (4-cyanobenzyloxy-l, 3-dihydro-1-hydroxy-2, 1-benzoxazole, 5- (2-cyanophenoxy) -1, 3-dihydro-l-hydroxy-2, 1-benzoxazole, 5-phenoxy-1,3-dihydro-l-hydroxy-2, 1-benzoxazole, 5- [4- (N, N-Diethylcarbamoyl) phenoxy] -1 , 3-dihydro-l-hydroxy-2, 1-benzoxazole, 1,3-Dihydro-l-hydroxy-5- [4- (morpholinocarbonyl) phenoxy] -2, 1-benzoxazole, 5- (3, 4-Dicyamphenoxy) ) -1, 3-dihydro-l-hydroxy-2, 1-benzoxazole, 6-phenylthio-1,3-dihydro-hydroxy-2, 1-benzoxazole, 6- (4-trifluoromethoxyphenoxy) -1, 3-dihydro- l-hydroxy-2, 1-benzoxazole, 5- (M-methyl-N-phenylsulfonylamino) -1, 3-dihydro-l-hydroxy-2, 1-benzoxazole, 6- (4-methoxyphenylthio) -1, 3-dihydro-hydroxy-2 , 1-benzoxazole, 6- (4-methoxyphenylthio) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole, 6- (4-methoxyphenylsulfinyl) -1, 3-dihydro-l-hydroxy-2, 1 -benzoxazole, 6- (4-methoxyphenylsulfinyl) -1, 3-dihydro-l-hydroxy-2, 1-benzoxazole, 5-trifluoromethyl-1,3-dihydro-hydroxy-2, 1-benzoxazole, 4- (4- Cyanophenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole, 5- (3-Cyanophenoxy) -1, 3-dihydro-l-hydroxy-2, 1-benzoxazole, 5- (4-carboxy-oxoxy) -1-hydroxy-2, 1-benzoxazole, l-Hydroxy-5- [4- (tetrazol-1-yl) phenoxy] -2, 1-benzoxazole, 4- (4- Cyanophenoxy) phenylboronic, 3- (4-cyano-phenoxy) -phenylboronic acid, and 4- (4-cyanophenoxy) -2-methylphenylboronic acid. In an exemplary embodiment, the compound has a structure that is a member selected from the following compounds: Methods for making the compounds In one aspect, the invention provides compounds useful in the methods. Preparation of Editing Domain Inhibitors Containing Boron Compounds for use in the present invention can be prepared using commercially available starting materials, known intermediates, or by using the synthesis methods published in references described and incorporated by reference herein. . Boronic Esters The following example reaction schemes illustrate methods for preparing boron-containing molecules of the present invention. These methods are not limited to producing the compounds shown, but can be used to prepare a variety of molecules such as the compounds and complexes described herein. The compounds of the present invention can also be synthesized by methods not illustrated or explicitly in the reaction schemes but are well within the skill of one in the art. The compounds can be prepared using readily available materials from known intermediates. In the following schemes, the symbol X represents bromine or iodine. The symbol Y is selected from H, lower alkyl, arialkyl lower and arialkyl. The symbol Z is select H, alkyl and aryl. The PG symbol represents a protective group. The symbols A, D, E, G, Rx, Ry, Rz, Rla, R2a, R3a, R4a, R5a, R6a, R7a, R8a, R9a, R10a, Rlla and R12a can be used to refer to the corresponding symbols and symbols. compounds described herein. Strategy No. 1 of Preparation of Boronic Acids In Reaction Scheme 1, Step 1 and 2, compounds 1 or 2 are converted to alcohol 3. In step 1, compound 1 is treated with a reducing agent in a solvent appropriate. Suitable reducing agents include borane complexes, such as borane-tetrahydrofuran, borane-dimethylsulfide, combinations thereof, and the like. Aluminum lithium hydride or sodium borohydride can also be used as reducing agents. Reducing agents can be used in amounts ranging from 0.5 to 5 equivalents, relative to compound 1 or 2. Suitable solvents include diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, combinations thereof and Similar. The reaction temperatures vary from 0 ° C to the boiling point of the solvent used; The reaction completion times vary from 1 to 24 hours. In Step 2, the carbonyl group of compound 2 is treated with a reducing agent in an appropriate solvent. Suitable reducing agents include borane complexes, such as borane-tetrahydrofuran, borane-dimethylsulfide, combinations thereof and similar. Aluminum lithium hydride or sodium borohydride can also be used as reducing agents. Reducing agents can be used in amounts ranging from 0.5 to 5 equivalents, relative to compound 2. Suitable solvents include lower alcohol, such as methanol, ethanol and propanol, diethyl ether, tetrahydrofuran, 1,4-dioxane and 1, 2-dimethoxyethane, combinations thereof and the like. The reaction temperatures vary from 0 ° C to the boiling point of the solvent used; reaction completion times vary from 1 to 24 hours. In step 3, the hydroxyl group of compound 3 is protected with a protecting group that is stable under neutral or basic conditions. The protecting group is typically selected from methoxymethyl, ethoxyethyl, tetrahydropyran-2-yl, trimethylsilyl, tert-butyldimethylsilyl, tributylsilyl, combinations thereof and the like. In the case of methoxymethyl, compound 3 is treated with 1 to 3 equivalents of chloromethyl methyl ether in the presence of a base. Suitable presences include sodium hydride, potassium tert-butoxide, tertiary amines, such as diisopropylethylamine, triethylamine, 1,8-diazabicyclo [5, 4, 0] undec-7-ene, and inorganic bases, such as sodium hydroxide. , sodium carbonate, potassium hydroxide, potassium carbonate, combinations thereof and the like.

The bases can be used in amounts ranging from 1 to 3 equivalents, relative to compound 3. The reaction temperatures vary from 0 ° C to the boiling point of the solvent used; preferably between 0 and 40 ° C; reaction completion times vary from 1 hour to 5 days. In the case of tetrahydropyran-2-yl, compound 3 is treated with 1 to 3 equivalents of 3,4-dihydro-2H-pyran in the presence of 1 to 10% in mol of acid catalyst. Suitable acidic catalysts include pyridinium-p-toluenesulfonic acid, p-toluenesulfonic acid, camphorsulfonic acid, methanesulfonic acid, hydrogen chloride, sulfuric acid, combinations thereof and the like. Suitable solvents include dichloromethane, chloroform, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, toluene, benzene and acrylonitrile, and combinations thereof and the like. The reaction temperatures vary from 0 ° C to the boiling point of the solvent used; preferably between 0 and 60 ° C, and is completed in 1 hour to 5 days. In the case of trialkylsilyl, compound 3 is treated with 1 to 3 equivalents of chlorotrialkylsilane in the presence of 1 to 3 equivalents of base. Suitable bases include tertiary amines, such as imidazole, diisopropylethylamine, triethylamine, 1,8-diazabicyclo [5, 40] undec-7-ene, combinations thereof and the like. The reaction temperatures vary from 0 ° C to boiling point of the solvent used; preferably between 0 and 40 ° C; reaction completion times vary from 1 to 48 hours. In Step 4, compound 4 is converted to boronic acid (5) through the halogen-metal exchange reaction. Compound 4 is treated with 1 to 3 equivalents of alkyl metal reagent relative to compound 4, such as n-butyllithium, sec-butyllithium, tert-butyl lithium, isopropylmagnesium chloride or Mg burrs with or without an initiator such as hydride diisobutylaluminum (DiBal), followed by the addition of 1 to 3 equivalents of trialkyl borate relative to compound 4, such as trimethyl borate, triisopropyl borate or tributyl borate. Suitable solvents include tetrahydrofuran, ether, 1,4-dioxane, 1,2-dimethoxyethane, toluene, hexanes, combinations thereof and the like. Alkylmetal reagent can also be added in the presence of trialkyl borate. The tributyl lithium addition is carried out between -100 and 0 ° C, preferably at least between 80 and 40 ° C. The addition of isopropylmagnesium chloride is carried out at -80 to 40 ° C, preferably at -20 to 30 ° C. The addition of Mg burrs, with or without the addition of DiBAl, is carried out between -80 and 40 ° C, preferably between -35 to 30 ° C. The addition of trialkyl borate is carried out between -100 and 20 ° C. After the addition of trialkyl borate, the reaction is Allow to warm to room temperature, which is typically -30 and 30 ° C. When the alkyl metal reagent is added in the presence of alkyl borate, the reaction mixture is allowed to warm to room temperature after the addition. The reaction completion times vary from 1 to 12 hours. Compound 5 can not be isolated and can be used for the next step without purification or in a kettle. In step 5, the protecting group of compound 5 is removed under acidic conditions to give the compound of the invention. Suitable acids include acetic acid, trifluoroacetic acid, hydrochloric acid, hydrobromic acid, sulfuric acid, p-toluenesulfonic acid and the like. The acids can be used in amounts ranging from 0.1 to 20 equivalents, relative to compound 5. When the protecting group is trialkylsilyl, basic reagents, such as tetrabutylammonium fluoride can also be used. Suitable solvents include tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, methanol, ethanol, propanol, acetonitrile, acetone, combinations thereof, and the like. The reaction temperatures vary from 0 ° C to the boiling point of the solvent used; preferably between 10 ° C and reflux temperature of the solvent. The reaction completion times vary from 0.5 to 48 hours. The product can be purified by methods known to those skilled in the art.

Reaction scheme 1 In another aspect, the invention provides a method for making a boronic ester containing tetrahydropyran, this ester having a structure according to the following formula: wherein R1 and R2 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. R1 and R2, together with the atoms to which they are attached, can optionally be attached to form a 4 to 7 membered ring. R9a, R10a, Rlla and R12a are members independently selected from H, OR *, NR * R **, SR *, - S (0) R *, -S (0) 2R *, -S (0) 2NR * R **, nitro, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. R * y R ** is a member selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. The method includes: a) submit a first compound to Grignard or organolithium conditions, the first compound having structure according to the following formula: b) contacting the product of step a) with a borate ester, thereby forming the boronic ester containing tetrahydropyran. In an exemplary embodiment, the halogen is a member selected from iodine and bromine. In another exemplary embodiment, the borate ester is a member selected from B (OR1) 2 (OR2), wherein R1 and R2 are each members independently selected from H, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, substituted propyl. or unsubstituted, substituted or unsubstituted isopropyl, substituted or unsubstituted butyl, substituted and unsubstituted t-butyl, substituted or unsubstituted phenyl and substituted or unsubstituted benzyl. R1 and R2, together with the atoms to which they are attached, can optionally form a member selected from substituted or unsubstituted dioxaborolane, substituted or unsubstituted dioxaborin and substituted or unsubstituted dioxaborepane. In another form of example, the borane ester is a member selected from B (OR1) 2 (OR2), wherein R1 and R2, together with the atoms to which they are attached, form a member selected from dioxaborolane, substituted or unsubstituted tetramethyldioxaborolane, phenyldioxaborolane substituted or unsubstituted, dioxaborin, dimethyldioxaborin and dioxaborepane. In another example embodiment, the Grignar or organolith conditions additionally comprise diisobutylaluminum hydride. In another example embodiment, the Grignard reaction temperature does not exceed about 35 ° C. In another example embodiment, the Grignard reaction temperature does not exceed approximately 40 ° C. In another example embodiment, the temperature of the Grignard reaction does not exceed about 45 ° C. In an exemplary embodiment, step (b) is performed at a temperature from about -30 ° C to about -20 ° C. In another example embodiment, step (b) is performed at a temperature from about -35 ° C to about -25 ° C. In another exemplary embodiment, step (b) is performed at a temperature from about -50 ° C to about -0 ° C. In another example embodiment, step (b) is carried out at a temperature from about -40 ° C to about -20 ° C. In another example embodiment, the boronic ester containing tetrahydropyran is In another aspect, the invention provides a method for making a compound having a structure according to the following formula the method comprising: a) subjecting a first compound to Grignard or organolithium conditions, the first compound having a structure according to the following formula: b) quench by subjecting the reaction with water and an organic acid, thereby forming the compound. In an exemplary embodiment, wherein the organic acid is a selected member of acetic acid. In another example embodiment, the extension step essentially does not contact a strong acid. In another exemplary embodiment, the compound is 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole. In another exemplary embodiment, the compound is purified by recrystallization from a recrystallization solvent, wherein the recrystallization solvent does not optionally contain acetonitrile. In an exemplary embodiment, the recrystallization solvent contains less than 2% acetonitrile. In an exemplary embodiment, the recrystallization solvent contains less than 1% acetonitrile. In an exemplary embodiment, the recrystallization solvent contains less than 0.5% acetonitrile. In an exemplary embodiment, the recrystallization solvent contains less than 0.1% acetonitrile. In an exemplary embodiment, the recrystallization solvent contains toluene and a hydrocarbon solvent. In an exemplary embodiment, the recrystallization solvent contains a solvent of about toluene: hydrocarbon 1: 1. In an exemplary embodiment, the recrystallization solvent contains a toluene: hydrocarbon solvent of about 2: 1. In an exemplary embodiment, the recrystallization solvent contains toluene: hydrocarbon solvent of about 3: 1. In an exemplary embodiment, the recrystallization solvent contains toluene: hydrocarbon solvent of about 4: 1. In an exemplary embodiment, the hydrocarbon solvent is a member selected from heptane, octane, hexane, pentane and nonano In an exemplary embodiment, the recrystallization solvent is toluene: heptane 3: 1 Strategy No. 2 Preparation of Boronic Acids In Reaction Scheme 2, Step 6, compound 2 is converted to boronic acid (6) by a reaction cross coupling catalyzed with transition metal. Compound 2 is treated with 1 to 3 equivalents of bis (pinacolato) diboron or 4,4,5,5,5-tetramethyl-l, 3,2-dioxaborlane in the presence of transition metal catalyst, with the use of appropriate ligand and appropriate basis as necessary. Suitable transition metal catalysts include palladium (II) acetate, acetoacetonate, palladium (II) acetoacetonate, tetrakis (triphenylphosphine) palladium, dichlorobis (triphenylphosphine) palladium, [1,1'-bis (diphenylphosphino) ferracene] dichloropalladium ( II), combinations thereof and the like. The catalyst can be used in amounts ranging from 1 to 5 mol% relative to compound 2. Suitable ligands include triphenylphosphine, tri (o-tolyl) phosphine, tricyclohexylphosphine, combinations thereof and the like. The ligand can be used in amounts ranging from 1 to 5 equivalents relative to compound 2. Suitable bases include sodium carbonate, potassium carbonate, potassium phenoxide, triethylamine, combinations thereof and the like. The base can be used in amounts ranging from 1 to 5 equivalents relative to compound 2.

Suitable solvents include N, N-dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, 1,4-dioxane, toluene, combinations thereof, and the like. The reaction temperatures vary from 20 ° C to the boiling point of the solvent used; preferably between 50 and 150 ° C; Reaction completion times vary from 1 to 72 hours. The pinacol ester is then cleaved oxidatively to give compound 6. The pinacol ester is treated with sodium periodate followed by acid. Sodium periodate can be used in amounts ranging from 2 to 5 equivalents relative to compound 6. Suitable solvents include tetrahydrofuran, 1,4-dioxane, acetonitrile, methanol, ethanol, combinations thereof and the like. Suitable acids include hydrochloric acid, hydrobromic acid, sulfuric acid, or combinations thereof and the like. The reaction temperatures vary from 0 ° C to the boiling point of the solvent used; preferably between 0 and 50 ° C; Reaction completion times vary from 1 to 72 hours. In step 7, the carbonyl group of compound 6 is treated with a reducing agent in a suitable solvent to give a compound of the invention. Suitable reducing agents include borane complexes, such as borane-tetrahydrofuran, borane-dimethylsulfide, combinations thereof, and the like. They can also be used as agents lithium aluminum hydride reducers or sodium borohydride. The reducing agents can be used in amounts ranging from 0.5 to 5 equivalents, relative to compound 6. Suitable solvents include lower alcohol, such as methanol, ethanol and propanol, diethyl ether, tetrahydrofuran, 1,4-dioxane and 1, 2-dimethoxyethane, combinations thereof and the like. The reaction temperatures vary from 0 ° C to the boiling point of the solvent used; reaction completion times vary from 1 to 24 hours. Reaction scheme 2 Strategy No. 3 of Preparation of Boronic Acid In Reaction Scheme 3, Step 8, the compounds of the invention can be prepared in one step from compound 3. Compound 3 is mixed with trialkyl borate then treated with reagent of alkyl metal. Suitable alkyl methanol reagents include n-butyllithium, sec-butyllithium, combinations thereof and the like. Suitable trialkyl borates include trimethyl borate, triisopropyl borate, tributyl borate, combinations thereof and the like. The addition of butyl lithium is carried out at least between 00 and 0 ° C, preferably between -80 and -40 ° C. The reaction mixture is allowed to warm to room temperature after the addition. The reaction completion times vary from 1 to 12 hours. Trialkyl borate can be used in amounts ranging from 1 to 5 equivalents relative to compound 3. The alkyl metal reagent can be used in amounts ranging from 1 to 2 equivalents relative to compound 3. Suitable solvents include tetrahydrofuran, ether, 1,4-dioxane, 1,2-methoxyethane, toluene, hexanes, combinations thereof and the like. The reaction completion times vary from 1 to 12 hours. Alternatively, a mixture of compound 3 and trialkyl borate can be refluxed for 1 to 3 hours and the alcohol molecule formed in the ester exchange can be distilled before the addition of the alkyl metal reagent. Reaction scheme 3 Strategy No. 4 of Preparation of Boronic Acids In Reaction Scheme 4, Step 10, the group methyl of compound 7 is brominated using N-bromosuccinimide. N-bromosuccinimide can be used in amounts ranging from 0.9 to 1.2 equivalents relative to compound 7. Suitable solvents include carbon tetrachloride, tetrahydrofuran, 1,4-dioxane, chlorobenzene, combinations thereof and the like. The reaction temperatures vary from 20 ° C to the boiling point of the solvent used; preferably between 50 and 150 ° C; reaction completion times vary from 1 to 12 hours. In step 11, the bromoethylene group of compound 8 is converted to benzyl alcohol 3. Compound 8 is treated with sodium acetate or potassium acetate. These acetates may be used in amounts ranging from 1 to 10 equivalents relative to compound 8. Suitable solvents include tetrahydrofuran, 1,4-dioxane, N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone. dimethylsulfoxide, combinations thereof and the like. The reaction temperatures vary from 20 ° C to the boiling point to the solvent used; preferably between 50 and 100 ° C; reaction completion times vary from 1 to 12 hours. The resulting acetate is hydrolyzed to compound 3 under basic conditions. Suitable bases include sodium hydroxide, lithium hydroxide, potassium hydroxide, combinations thereof and the like. The base can be used in amounts ranging from 1 to 5 equivalents in relation to the compound 8. Suitable solvents include methanol, ethanol, tetrahydrofuran, water, combinations thereof and the like. The reaction temperatures vary from 20 ° C to the boiling point of the solvent used; preferably between 50 and 100 ° C; reaction completion times vary from 1 to 12 hours. Alternatively, compound 8 can be converted directly to compound 3 under the above similar condition. Steps 3 to 5 convert compound 3 to a compound of the invention. Reaction scheme 4 Strategy No. 5 for Preparation of Boronic Acids In Reaction Scheme 5, Step 12, compound 2 is treated with (methoxymethyl) triphenylphosphonium chloride or (methoxymethyl) triphenylphosphonium bromide in the presence of base followed by acid hydrolysis to give the compound 9. Suitable bases include sodium hydride, potassium tert-butoxide, lithium diisopropylamide, butyllithium, lithium hexamethyldisilazane, combinations thereof and the like. The (methoxymethyl) triphenylphosphonium salt can be used in amounts ranging from 1 to 5 equivalents relative to compound 2. The base can be used in amounts ranging from 1 to 5 equivalents relative to compound 2. Suitable solvents include tetrahydrofuran , 1,2-dimethoxyethane, 1,4-dioxane, ether, toluene, hexane, N, N-dimethylformamide, combinations thereof and the like. The reaction temperatures vary from 0 ° C to the boiling point of the solvent used; preferably between 0 and 30 ° C; reaction completion times vary from 1 to 12 hours. The enolter formed is hydrolyzed under acidic conditions. Suitable acids include boronic acid, hydrobromic acid, sulfuric acid, and the like. Suitable solvents include tetrahydrofuran, 1,2-dimethoxyethane, 1,4-dioxane, methanol, ethanol, combinations thereof and the like. The reaction temperatures vary from 20 ° C to the boiling point of the solvent used; preferably between 50 and 100 ° C; reaction completion times vary from 1 to 12 hours. Steps 2 to 5 convert step 9 to a compound of the invention Reaction Scheme Strategy No. 6 for Preparation of Boronic Acids In Reaction Scheme 6, the compound (I) wherein R1 is H and is converted to the compound (I) wherein R1 is alkyl by mixing with the corresponding alcohol, R1OH. Suitable solvents include tetrahydrofuran, 1,2-dimethoxyethane, 1,4-dioxane, toluene, combinations thereof, and the like. Alcohol (R1OH) can be used as the solvent as well. The reaction temperatures vary from 20 ° C to the boiling point of the solvent used; preferably between 50 and 100 ° C; The reaction completion times vary from 1 to 12 hours.

Reaction scheme 6 II, R ^ H, II, Rl? H Strategy No. 7 for Preparation of Boronic Acids In Reaction Scheme 7, compound (a) is converted to its aminoalcohol complex (Ib). The compound is treated with HOR1NRlaRlb. The aminoalcohol can be used in amounts ranging from 1 to 10 equivalents relative to the compound (la). Suitable solvents include methanol, ethanol, propanol, tetrahydrofuran, acetone, acetonitrile. 1,2-dimethoxyethane, 1,4-dioxane, toluene, N, N-dimethylformamide, water, combinations thereof and the like. The reaction temperatures vary from 20 ° C to the boiling point of the solvent used; preferably between 50 and 100 ° C; reaction completion times vary from 1 to 24 hours. Reaction scheme 7 The compounds of the invention can be converted to hydrates and solvates by methods similar to those described above. I. c) Borinic Esters In one aspect, the invention provides compounds useful in methods having a structure according to Formula XI: wherein the variables Rlc, A, D, E, G, J, W and M are described elsewhere in the present. In an exemplary embodiment of Formula (XI), Rlc is unsubstituted substituted (Ci-C4) alkyl. In an exemplary embodiment of Formula (XI), Rlc is substituted or unsubstituted alkyloxy. In an exemplary embodiment of Formula (XI), Rlc is substituted or unsubstituted cyclo (C3-C7) cycloalkyl. In an exemplary embodiment of Formula (XI), Rlc is substituted or unsubstituted alkenyl. In a further exemplary embodiment thereof, the substituted alkenyl has the structure wherein R, R c and R are members independently selected from H, haloalkyl, aralkyl, substituted aralkyl (CH2) iOH (where r = 1 to 3), CH2NR26cR27c (wherein R26c and R27c are independently selected from hydrogen and alkyl), C02H, C02alkyl, CONH2, S-alkyl, S-aryl, S02alkyl, S03H, SCF3, CN, halogen, CF3, N02, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. In another exemplary embodiment of Formula (XI), Rlc is a substituted or unsubstituted alkynyl. In an exemplary further embodiment thereof, the substituted alkynyl has the structure where R¿ SC is defined as before. In an exemplary embodiment of Formula (XI), Rlc is substituted or unsubstituted aryl. In a further exemplary embodiment thereof, the substituted aryl has the structure (XIV) wherein R28c, R29c, R30c, R31c and R32c are each independently selected from H, aralkyl, substituted araylkyl, (CH2) sOH (where s = 1 to 3), C02H, C02alkyl, CONH2 CONHalkyl, CO ( alkyl) 2, OH, alkoxy, aryloxy, SH, S-alkyl, S-aryl, S02alkyl, S03H, SCF3, CN, halogen, CF3, N02 (CH2) tNR26R27 (where R26 and R27 are independently selected from hydrogen, alkyl, and alkanoyl) (t = 0 to 2), S02NH2, 0CH2CH2NH2, 0C2CH2NHalkyl, 0CH2CH2N (alkyl) 2, oxazolidin-2-yl, oxazolidin-2-yl substituted with alkyl, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted cycloalkyl or unsubstituted, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and heteroaryl. In an exemplary embodiment of Formula (XI), Rlc is substituted or unsubstituted aralkyl. In a further exemplary embodiment thereof, the substituted aralkyl has the structure. wherein Rou, R ^, RJUU, RJ1U and are defined as above, and is not an integer selected from 1 to 15. In an exemplary embodiment of Formula (XI), Rlc is a substituted or unsubstituted heteroaryl. In an additional example mode of themiscary, the heteroaryl has the structure wherein X is a member selected from CH = CH, N = CH, NR (where R35c = H, alkyl, aryl or benzyl), O, or S. Y = CH or N. R33c and R3 c are each members independently selected from H, haloalkyl, aralkyl, substituted aralkyl, (CH2) uOH (where u = 1, 2 or 3), (CH2) vNR26cR27c (wherein R26c and R27c are independently selected from hydrogen, alkyl and alkanoyl) (v = 0 to 3), C02H, C02 alkyl, C0NH2, S-alkyl, S-aryl, S02alkyl, S03H, SCF3, CN, halogen, CF3, N02, substituted or unsubstituted alkyl, substituted heteroalkyl or unsubstituted, cycloalkyl substituted or unsubstituted, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. The structures of the invention also allow interactions of solvents that can give structures (Formula XVII) include atoms derived from the solvent found by the compounds of the invention during synthetic manipulations and therapeutic uses. Structure XVII arises from the formation of a dative bond between the solvents with the Lewis acid boron center. In this way, these solvent complexes can be stable entities with comparative bioactivities. These structures are expressly contemplated by the present invention wherein R40c is H or alkyl.

Formula (XVII) In an exemplary embodiment, the invention provides a structure that is a selected member of Formula (Ic), (lie) and (IIIc): (Ic); (lie); where B is boron, ql and q2 are integers independently selected from 1 to 3. q3 is an integer selected from 0 to 4. M is a member selected from H, halogen, -OCH3, and -CH2-0-CH2 -0-CH3. M1 is a member selected from halogen, -CH2OH, and -OCH3. X is a member selected from 0, S and NRXC. Rxc is. a member selected from H and substituted or unsubstituted alkyl. Rlc, R3c, Rc, R2c and R5c are independently selected from H, OH, SN2, SH, CN, N02, S02, 0S020H, OS02NH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted heterocycloalkyl or unsubstituted, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. R41c is a member selected from substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted hearoarylalkyl and substituted or unsubstituted vinyl. The compounds of the invention can form a hydrate with water, solvates with alcohols such as methanol, ethanol, propanol and the like; adducts with amino compounds, such as ammonia, methylamine, ethylamine, and the like; adducts with acids, such as formic acid, acetic acid and the like; complexes with ethanolamine, quinoline, amino acids, and the like. In an exemplary embodiment, the compound has a structure that is a member selected from 2- (3-chlorophenyl) - [1,2,3] -dioxaborolane, (3-chlorophenyl) (4 '-fluoro- (2') acid - (methoxymethoxy) -methyl) -phenyl) -borinic acid, 1- (3-chlorophenyl) -5-fluoro-1,3-dihydrobenzo [c] [1,2] oxaborol, 1- (3-chlorophenyl) -6- fluoro-1, 3-dihydrobenzo [c] [1, 2] oxaborol, 1- (3-chlorophenyl) -1, 3-dihydrobenzo [c] [1, 2] oxaborol, 5-chloro-l- (3-fluorophenyl) ) -1, 3-dihydrobenzo [c] [1, 2] oxaborol, 2- (3-fluorophenyl) - [1, 3, 2] -dioxaborolane, 3- (benzo [c] [1, 2] oxaborol-1 (3H) -yl) benzonitrile, 2- (3-cyanophenyl) - [1, 3, 2] -dioxaborolane, (3-chlorophenyl) (5 { -fluoro- (2 '~ (methoxymethoxy) methyl) - phenyl) -borinic acid, 1- (3-chlorophenyl) -1,3-dihydro-3, 3dimethylbenzo [c] [1,2] oxaborol, (3-chlorophenyl) (2- (2- (methoxymethoxy) propan-2-yl) ) phenylborinic acid, 1- (3-chlorophenyl) -1,3-dihydro-3, 3-dimethylbenzo [c] [1,2] oxaborol, 1- (4-chlorophenyl) -1,3-dihydrobe nzo [c] [1, 2] oxaborol, 2- (-chlorophenyl) - [1, 3, 2] -dioxaborolam, 4- (benzo [c] [1, 2] oxaborol-1 (3H) -yl) benzonitrile , 2- (4-cyanophenyl) - [1,3,2] -dioxaborolane, 4- (5-fluorobenzo [c] [1, 2] oxaborol-1 (3H) -yl) benzonitrile, 2- (4-cyanophenyl) ) - [1, 3, 2] -dioxaborolane, 3- (5- fluorobenzo [c] [1, 2] oxaborol-1 (3H) -yl) benzonitrile, 2- (3-cyanophenyl) - [1,3,2] -dioxaborolane, -3- (6-fluorobenzo [c] [1 , 2] oxaborol-1 (3H) -yl) enzonitrile, 2- (3-iaiophenyl) - [1,3,2] -dioxaborolane, 1- (3-cyanophenyl) -5,6 · dimethoxy-1, 3- dihydrobenzo [c] [1,2] -oxaborol, 2- (3-chlorophenyl) [1, 3, 2] -dioxaborolane, (- (5- (fluorobenzo [c] [1, 2] oxaborol 1 (3H) -yl) phenylmethanamine, 5-fluoro-2- (methoxymethoxymethyl) phenyl [1, 3, 2] -dioxaborolane, 4- (5- (fluorobenzo [c] [1,2] oxaborol 1 (3H) -yl) phenylmethanamine, (3- (5- (fluorobenzo [c] [1, 2] oxaborol 1 (3H) -yl) -phenylmethanamine, (4- (5- (fluorobenzo [c] [1, 2] oxaborol 1 (3H) -yl) phenyl) methanol, (3- (5- (fluorobenzo [c] [1, 2] oxaborol 1 (3H) -yl) phenyl) methanol, 3- (6-fluorobenzo [c] [1,2] oxaborol 1 (3 H) -yl) phenol, 3- (5-fluorobenzo [c] [1, 2] oxaborol-1 (3 H) yl) pyridine, (2- (benzo [c] [1,2] oxaborol-1) acid (3H) il) phenyl) methanol, 2- [(methoxymethoxy) methyl] phenylboronic, 2 [(methoxymethoxymethyl) phenyl] - [1,2, 2] -dioxaborolane, bis [2 (methoxymethoxymethyl) phenyl] boronic acid, (2) - (benzo [c] [1, 2] oxaborol 1 (3H) -yl) phenyl) methanol, (2- (benzo [c] [1,2] oxaborol-1 (3H) yl) phenyl) -N, - dimethylmethanamine, (2- (benzo [c] [1,2] oxaborol 1 (3H) -yl) -5-chlorophenyl) -N, -dimethylmethanamine, (2 (benzo [c] [1,2] oxaborol-1 ( 3H) -yl) -5-chlorophenyl) methanol, (2 (BENZ0 [c] [1, 2] oxaborol-1 (3H) -yl) -5-chlorophenyl) methanol, (5-chloro-2- (5-chlorobenzo [c] [1,2] oxaborol-1 (3H) -yl) phenyl) methanol, bis [4-chloro-2- (methoxymethoxymethyl) phenyl] boronic acid, (5-chloro-2- (5-chlorobenzo [c]] [1,2] oxaborol-1 (3H) -yl) phenyl) methanol, (5-chloro-2- (5-chlorobenzo [c] [1,2] oxaborol-1 (3H) -yl) phenyl-N, N-dimethylmethanamine, 1- (4-chloro-2-methoxyphenyl) -1, 3-dihydrobenzo [c] [1,2] benzoxazole, ethylene glycol ester of 4-chloro-2-methoxyphenylboronic acid, 1- (4-chloro-2-methoxyphenyl) -1,3-dihydrobenzo [c] [1, 2] ] benzoxazole, 2- (benzo [c] [1, 2] oxaboral-1 (3H) -yl) -5-chlorophenol, 2- (3- (benzo [c] [1,2] oxaborol-1 (3H) -il) phenoxy) -5-chlorophenol, 2- (3- (benzo [c] [1,2] oxaborol-1 (3H) -yl) phenoxy) -5-chlorophenol 4 - ((3- (5-fluorobenzo [c] [1, 2] oxaborol-1 (3H) -yl) phenyl) methyl) morpholine, 3- (5-fluorobenzo [c] [1, 2] oxaborol-1 (3H) -yl] phenyl) -methyl 8-hydroxy-quinoline-2-carboxylate, 1- (3-chlorophenyl) -2,3-dihydro-2- (methoxymethi) -β-benzo [c] [1,2] azaborol, 3-chlorophenyl 2- [N, N-bis (methoxymethyl) aminomethyl] phenylboronic acid, 1- (3-chlorophenyl) -2,3-dihydro-2- (methoxymethyl) -1H-benzo [c] [1,2] azaborol, 1- (3-chlorophenyl) ) -1, 3, 4, 5-tetrahydrobenzo- [c] [1,2] -oxaborepine, 1- (3-chlorophenyl) -1,3,4,5-tetrahydrobenzo [c] [1,2] oxaborepine, 1- (3-chlorophenyl) -3,4-dihydro-lH-benzo [c] [1,2] -oxaborinin, 2- (3-chlorophenyl) - [1, 3, 2] dioxaborlane, (3-chlorophenyl) acid ) (2 '- (2- (methoxymethoxy) ethyl) phenyl) boronic, and 1- (3-chlorophenyl) -3,4-dihydro-lH-benzo [c] [1,2] oxaborinino. I. d.) Preparation of Compounds Containing Boron Compounds for use in the present invention can be prepared using commercially available starting materials, known intermediates, or by using a synthesis method published in the references described and incorporated by reference herein. I. e.) Boronic Esters Methods for making boronic esters are known in the art, and it is within the knowledge of one skilled in the art to use these methods in order to make the boronic esters described herein. Examples include U.S. Patent Nos. 10 / 740,304,10 / 867,465, 11 / 152,959, 11 / 153,765, 11 / 153,010, 11 / 389,605, 11 / 389,605, 11 / 357,687, 11 / 357,687 and provisional patents of the United States. United Nos. 60 / 754,750, 60 / 774,532 and 60 / 746,361, which are incorporated herein by reference. Another example of a synthesis route for the preparation of compounds for use in the invention is shown below: I. f.) Borinic Esters Methods for making borinic esters are known in the art, and it is within the knowledge of one skilled in the art to use these methods in order to make the boronic esters described herein. Examples include U.S. Pat. Nos. 10 / 868,268, and 11 / 743,665 which are incorporated herein by reference.

II. Assays for Inhibition of Periodontal Disease The recognized techniques of genetics and molecular / cellular biology are of use to identify compounds that are appropriate for inhibition of periodontal disease. Examples of tests used for this determination are provided herein. III. Oral Care Compositions In another aspect, the present invention provides an oral care composition comprising a compound of the invention. In an exemplary embodiment, the compound is a boron-containing compound described herein. In another exemplary embodiment, the compound is a member selected from 3-hydroxypyridine-2-carbonyloxy-bis (3-chloro-4-methylphenyl) -borane, 3-hydroxy-piolinate ester of (bis (3-chloro-4) -acid methylphenyl) borinic acid, 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole, and 5- (4-cyanophenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole. another example embodiment, the compound is 3-hydroxypyridine-2-carbonyloxy-bis (3-chloro-4-methylphenyl) - borane (bis (3-chloro-4-methylphenyl) boronic acid 3-hydroxypicolinate ester These oral care compositions are of use in the methods of the invention An oral care composition of the present invention can take any physical form suitable for application to an oral surface In various illustrative embodiments, the composition may be a suitable liquid solution for irrigating, rinsing or spraying; a dentifrice such as a powder, toothpaste or dental gel; a liquid suitable for painting a surface dental (e.g., a liquid bleach); or a chewing gum; a soluble, partially soluble or insoluble strip or film (e.g., a bleaching strip); a wafer; a wipe or rinse; an implant; a dental floss; toothpastes, prophylactic pastes, tooth wax, gels, professional gels and other related products applied by dentists, as well as mouthwashes, mouthwashes, dental floss s, chewing gums, pills, tablets, edible foodstuffs, periochips for insertion into periodontal cavities (made of material such as chlorhexidine gluconate) and the like. The composition may contain additional active ingredients and / or carriers to those cited above. In certain embodiments of the invention, a compound described herein in the oral care composition is It can encapsulate a material called a microsphere. This material can act as a slow release mechanism for the compound. In the exemplary embodiment, the microsphere is constructed at least partially from chitosan. In an exemplary embodiment, 3-hydroxypyridine-2-carbonyloxy-bis (3-chloro-4-methylphenyl) -borane is encapsulated in a micro sphere in an oral care composition. Additional descriptions of microencapsulated materials are described in Govender et al., Journal of Microencapsulation, 23 (7): November 2006, pp 750-761, which are incorporated herein by reference. In certain embodiments, the composition is adapted for application to an oral surface of a small pet, for example a cat or a dog. This composition is typically edible or chewable by the animal, and may take the form, for example, of a cat or dog food, a gift or toy. Illustratively, the composition of any of the embodiments described above is a mouth wash or rinse, an oral spray, a dentifrice, an oral strip, a liquid bleach or a chewing gum. Rinses include liquids adapted for irrigation by means of devices such as high pressure water jets. Toothpastes include, without limitation, toothpastes, gels and powders. A "liquid bleach" encompasses the present semi-liquid composition such as gels as well as fluid liquids, while the composition is capable of application to a tooth surface by painting with a brush or other suitable device. "Painting" in the present context means application of a thin layer of the composition to the tooth surface. In one embodiment, the composition is a toothpaste or gel dentifrice. A composition of the invention may comprise, in addition to the boron-containing compound described herein, a vitamin or vitamin derivative or antioxidant component or one or more active ("active") agents. Other useful active components are those that face, without limitation, the appearance and structural changes to the teeth, treatment and prevention of plaque, calculus, dental caries, caries, abscesses, swollen and / or bleeding gums, gingivitis, inflammatory conditions and / or oral infectious in general, sensitivity of teeth, halitosis and the like. In this manner, a composition of the invention may contain one or more active agents such as bleaching agents, fluoride ion sources, additional antimicrobial agents to the boron-containing compound described herein, desensitizing agents, anticalculus agents (tartar control), sources of stannous ions, sources of zinc ions, sialagogues, breath fresheners, agents antiplaque, anti-inflammatory agents, in addition to any compound containing boron that has anti-inflammatory properties, periodontal agents, analgesics and nutrients. Active agents must be selected for compatibility with each other and with other ingredients of the composition. The active agents useful herein are usually present in the composition in amounts selected as safe and effective, i.e., sufficient to provide a desired benefit, for example, a therapeutic, prophylactic, nutritional or cosmetic effect, when the composition is used. repeatedly as described herein, without undue side effects such as toxicity, irritation or allergic reaction, in proportion to a reasonable risk / benefit ratio. This safe and effective amount usually fall, but not necessarily, within appropriate intervals by appropriate regulatory agencies. An effective and safe amount in a specific case depends on many factors, including the particular benefit desired or the condition being treated or sought to be prevented, the particular subject using, or being administered, the composition, frequency and duration of use, etc. The active agents are typically present in a total amount of from about 0.01% to about 80%, for example, from about 0.05% to about 60%, from about 0.1% to about 50%, or from about 0.5% to about 40%, by weight of the composition. One or more active agents, including the boron-containing compound described herein, may optionally be present in encapsulated form in the composition. For example, beads containing one or more active agents can be adapted to break during brushing or chewing to release the active agents to the oral surface. Additionally, the composition of the invention may include any of the components conventionally present or desirable in an oral care product. For example, the composition may include a bleaching agent, such as peroxy compounds, chlorine oxide, chlorites and hypochlorites, a polymer-peroxide complex, polyvinylpyrrolidone-hydrogen peroxide complex (PVP-H202); a source of fluoride ions (monofluorophosphate and fluorosilicate salts, antibacterial agents) Active agents such as antibacterial agents may include, those listed in U.S. Patent No. 5,776,435 to Gaffar et al. of which they are incorporated herein by reference The composition may additionally include a tooth anti-sensitivity agent, a sialagogue (saliva stimulating agent), a Breathing agent of breath, a people breaking plaque or antiplaque. Among the useful carriers for optional inclusion in a composition of the invention are diluents, abrasives, bicarbonate salts, pH modifying agents, surfactants, foam modulators, thickening agents, viscosity modifiers, humectants, sweeteners, flavors and colorants. A carrier material, or more than one carrier material of the same or different kind, may optionally be present. Water is a preferred diluent and in some compositions such as mouthwashes and bleaching liquids may be accompanied by an additional solvent, such as an alcohol, for example, ethanol. The composition may contain abrasives, pH modifying agents, surfactants, foam modulators, thickening agents, viscosity modifiers, humectants, sweeteners, flavors, colorants. The invention further provides an oral care method comprising a step of applying a composition as described herein to an oral surface of a subject. In one embodiment, the composition is a toothpaste or a gel dentifrice, and the application step comprises brushing the surface, eg, a tooth surface and a periodontal surface adjacent thereto, with the toothpaste According to one embodiment of the invention, there is further provided a method for inhibiting inflammation in an oral tissue of a subject. The method of this embodiment comprises applying a compound of the invention to an oral surface close to the tissue. In an exemplary embodiment, the compound is a member selected from 3-hydroxypyridine-2-carbonyloxy-bis (3-chloro-4-methylphenyl) -borane (3-hydroxy-piolinate ester of bis (3-chloro-4-methylphenyl) acid. borinic acid), 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole, and 5- (4-cyanophenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole. In another example embodiment, the compound is 3-hydroxypyridine-2-carbonyloxy-bis (3-chloro-4-methylphenyl) -borane. In another embodiment, a method for promoting oral health in a subject is provided. The method of this embodiment comprises applying a compound of the invention to an oral surface of the subject. The practice of a method of the invention can promote any aspect or aspects of oral health. As an example, this method can promote periodontal and / or gingival health, for example by reducing bacterial infection and / or inflammation. As another example, this method can provide a benefit to freshen breath, for example through antibacterial and / or antioxidant activity. As yet another example, this method can promote retention of the teeth, for example, by reducing or preventing tooth decay and by preventing the destruction of the bone matrix that holds the tooth in place. As yet another example, this method can provide an anti-plaque benefit. As yet another example, this method can reduce the damage to oral tissues from free radicals, including those that occur as a result of contact with tobacco smoke or contaminated air. It is well known that improved oral health, in particular improved periodontal and / or gingival health, associated with reduced bacterial infection and / or reduced inflammation can lead to systemic or whole body health benefits. The distribution of vitamins by the oral surface as provided herein may further improve overall health by supplementing the vitamins ingested with the food. Among the systemic conditions that can be improved as a result of improved oral health following the practice of the method of the invention are cardiovascular disease including atherosclerosis, coronary heart disease (CHD) and stroke; diabetes; respiratory infections including bacterial pneumonia; low weight of preterm birth; stomach ulcers; bacteremia, infectious endocarditis; prosthetic device infection; chronic obstructive pulmonary disease (COPD); and abscesses cerebral. The practice of the methods may consist of an individual application as described herein, or may comprise repeating these applications. In one embodiment, a method as described herein is repeated at regular intervals, for example twice or once a day, twice or once a week, twice or once a month, in a program or regime carried out at home and / or in a clinical or professional setting. The subject in any of the above methods can be a human or non-human mammal, for example, a dog, cat, horse or exotic mammal. In certain embodiments, the subject is a small domestic animal, for example, a cat or a dog, and the composition, in the form of a food, gift or toy, is given to the animal to chew. The oral care compositions of this invention may additionally include a variety of other components, including hydrophilic liquid carriers, including but not limited to glycerin, propylene glycol, polyethylene glycol, and hydrophobic liquid carriers such as triglyceride, diglyceride, and organic oils including mineral oil , essential oils, and fatty vegetable oils. These hydrophilic and hydrophobic liquid carriers can be used either individually or in combination and preferably, they can be added in a proportion of about 2 to about 50% by weight (in the case of compositions comprising liquid carriers), especially from about 10 to about 35% based on the complete composition. Using one or more of these liquid carriers, the composition of the present invention for the oral cavity can preferably be formulated in a use form such as gel, liquid or paste. The oral care compositions of the present invention may also contain flavor components, typically in the form of natural flavors or aromatic oils and / or herbal extracts and oils. These flavor components may serve not only to impart a flavor to the oral care composition, but may act as natural and preservative antibacterial agents at the same time. Oils suitable for use in the present invention include but are not limited to citrus oil, lemon oil, lime oil, lemon grass oil, orange oil, sweet orange oil, grape oil, pomegranate oil, chabacano oil extract, tangerine extract, tangelo oil, peppermint oil, peppermint oil, sage oil, rosemary oil, cinnamon oil, wintergreen oil, garlic clove oil, eucalyptus oil, olive oil ginger, sassafras oil, menthol, mint arvensis oil, flavors and oils of synthetic mint, carvona, eugenol, methyleugenol, salicylate methyl, methyl eugenol, thymol, anethole, millefolium extract, chamomile, lavender oil, myrrh, eugenol, tea tree oil, sage oil, mallow, limonene, ocimene, n-decyl alcohol, citronellol, a-terpineol , linalool, etillinalol, thyme, almond oil, nutmeg, and vanilla. Any of these flavors or a mixture of two or more of these flavors can be used in the dentifrice composition. The content thereof ranges from about 3% to about 20% by weight, such as from about 4% to about 15% by weight, based on the complete composition. Silica abrasives may also be incorporated into the oral care composition of the present invention, without departing from the scope of the invention. Specific silica abrasives suitable for use with the present invention include but are not limited to silica gels, precipitated silicas, silicates, and hydrated silica. Silica gels suitable for use with the present invention are hydrogels, hydrated gels, xerogels and gels, such as those known in the art and described in U.S. Patent No. 6,440,397. Precipitated silicas are those known in the art, such as the precipitated oral care type silicas described in U.S. Patent No. 5,589,160. Suitable silicates are any of those that occur naturally or synthetic silicates suitable for use with oral care compositions. Silica abrasives can be used individually or in combination. An exemplary silica abrasive for use with the present invention includes silica gels. Silica abrasives can be used in conjunction with the calcium salt or in place of the calcium salt component. Optionally, water can be incorporated into the compositions of. oral care of the present invention, such as toothpaste and mouthwashes. The water used in the preparation of commercially suitable oral care compositions should preferably be deionized and be free of organic impurities. In general, water may comprise from about 0% to about 40% by weight of the toothpaste compositions herein. In addition to the components described above, the oral care composition of the present invention may further contain a variety of optional ingredients and vehicles in general used for preparations for use in the oral cavity, such as toothpaste and mouthwashes. These optional components include, but are not limited to, components such as abrasives, surfactants, thickening agents, buffers, humectants, preservatives, and antibiotic and anti-caries agents. All these additives, described in additional detail below, are generally usual and will be known to one skilled in the art. The dental abrasives useful in the dentifrice compositions of the present invention include a variety of different materials known in the art. Preferably, the abrasive material should be one that is compatible with the composition of interest and does not excessively erode the dentin. Suitable abrasives include, for example, silicas including gels and precipitated products; insoluble polymetaphosphates, hydrated alumina, resinous abrasives such as polymerized resins (e.g., ureas, melamines, cross-linked epoxies, phenolics and the like), and mixtures thereof. Another optional component of the oral care compositions of the present invention is a humectant. The humectant serves to prevent compositions such as toothpaste compositions from hardening on exposure to air, and gives the mouthwash and toothpaste compositions a moist mouth feel. Certain humectants can also impart adequate flavor sweetness to toothpaste and mouthwash compositions. Suitable humectants for use in the compositions of the present invention include edible polyhydric alcohols such as glycerin, sorbitol, xylitol, polyethylene glycol, and propylene glycol. The oral care compositions of the present invention may also optionally contain sweeteners, such as sodium saccharin, acesulfame potassium, glycyrrhizin, perilartin, thaumatin, aspartylphenylalanine methyl ester and xylitol. Buffering agents are another optional component for the oral care compositions of the present invention. Buffering agents serve to retain the pH of the compositions within the preferred range. Buffering agents suitable for use in the dentifrice compositions of the present invention include soluble phosphate salts. Other optional components of the oral care compositions of the present invention are preservatives, such as those that prevent the microbial growth of oral care compositions. Suitable preservatives include but are not limited to methylparaben, propylparaben, benzoates, and alcohols such as ethanol. Optionally, binders and thickeners can also be used in the oral care compositions of the present invention, particularly in toothpaste compositions. Preferred thickeners and binders include, but are not limited to, carragahen (e.g., viscarin, Irish moss, and the like); cellulose derivatives such as hydroxyethyl cellulose, sodium carboxymethyl cellulose, and sodium carboxymethyl hydroxypropyl cellulose, polymers of carboxyvinyl; natural gums, such as karaya gum, gum arabic and tragacanth; pillisaccharide gums such as xanthan gum; fumed silica, and colloidal magnesium aluminum silicate. The compositions of the present oral care compositions may also optionally contain a surfactant. Suitable surfactants are those which are reasonably stable and preferably form soap scum (bubbles) throughout the pH range of the dentifrice compositions. Surfactants may also be added to act as solubilizing agents to help retain sparingly soluble components in solutions or mixtures. Surfactants useful in dentifrice compositions as soap-sudsing agents may be soaps, polysorbates, poloxamers, and synthetic detergents that are anionic, nonionic, cationic, zwitterionic, or amphoteric and mixtures thereof. The oral care compositions of the present invention may also optionally comprise anti-caries agents. Preferred anti-caries agents are water-soluble fluoride ion sources. The number of these fluoride ion sources is large and well known to those skilled in the art, and includes those described in U.S. Patent No. 3,535,421. The Example fluoride ion source materials include sodium fluoride, potassium fluoride, sodium monofluorophosphate and mixtures thereof. Also, antimicrobial and anti-tartar agents may optionally be present in the oral care compositions of the present invention. These agents may include, triclosan (5-chloro-2- (2,4-dichlorophenoxy) -phenol); chlorhexidine; chlorhexidine digluconate (CHX); alexidine, hexetidine (HEX); sanguinarine (SNG); benzalkonium chloride; salicylanilide; domiphene bromide; cetylpyridinium chloride (CPC); tetradecylpyridinium chloride (TPC); N-tetra-decyl-4-ethylpyridinium chloride (TDEPC); octenidine; delmopinol; octapinol, and other piperidino derivatives; nicine preparations; zinc / stannous ion agents; antibiotics such as augmentin, amoxicillin, tetracycline, deoxycycline, minocycline, and metronidazole; peroxide, such as cilium peroxide, hydrogen peroxide, and magnesium monopertalate and their analogues; and analogues and salts of the antimicrobial and anti-tartar agents listed above. The oral care compositions of the present invention may also optionally include one or more anti-calculus (anti-tartar) agents. Anti-calculus agents that may be useful in the dentifrice compositions of the present invention include antimicrobials such as chlorhexidine, nidamycin, and triclosan, metals and salts Metals such as zinc citrate, Vitamin C, bisphosphonates, triclosanpyrrophosphates, pyrophosphates, polyphosphates, polyacrylates and other polycarboxylates, polyepoxysuccinates, ethene diaminetetraacetic acid, (EDTA), nitrilotriacetic acid and related compounds, polyphosphonates, and polypyrrophosphates such as sodium hexametaphosphate, as well as other anti-calculus agents known to those skilled in the art, such as those described in KJ Fairbrother et al., "Anticalculus agents", Journal of Clinical Periodontology Vol. 27, pp. 285-301 (2000). Nutrients and vitamins may also be added to the oral care compositions of the present invention. These agents may include foliates, retinoids (vitamin A), vitamin B (thiamine, B2-riboflavin, B3-niacin, B5-pantothenic acid, B6-pyridoxine, B7-biotin, B8 / Bg / Bc-folic acid, Bi2-cyanocobalamin), Vitamin C (ascorbic acid, sodium ascorbate), Vitamin E, Vitamin E analogues (dl-a-tocopheryl acetate, tocopherol succinate, tocopherol nicotinate) and zinc. Optionally, a variety of miscellaneous additives may also be formulated in the oral care compositions of the present invention, such as tooth desensitizing agents (e.g., potassium and strontium salts), condensed anti-tartar agents such as sodium tetrapyrrophosphate and potassium, bleaching agents such as rust aluminum and calcium peroxide, exfoliating agents such as sodium bicarbonate, pigments and dyes, such as Blue 15-C174160, Green 7-C174260, Reds 4-CI12085 and 40-CI16035, Yellows I15-CI47005: 1 and 5-CI19140, and Carmine 5-CI16035), as well as additives such as mica and sparks. As with the other optional oral care additives, either of these ingredients or a mixture of two or more of these ingredients may be used in amounts appropriate for the oral care composition. IV. Methods for inhibiting the Growth of Microorganisms or for Annihilating Microorganisms In a further aspect, the invention provides a method for inhibiting the growth, or for killing, a microorganism, preferably a bacterium, fungus, virus, yeast or parasite, comprising in contact the organism with a compound of the invention. In an exemplary embodiment, the compound is a boron-containing compound described herein. In an example embodiment, the microorganism is in the oral cavity of an animal, which is a selected member of human, cattle, deer, reindeer, goat, bee, pig, sheep, horse, cow, bull, dog, guinea pig, gerbil. , rabbit, cat, camel, yak, elephant, ostrich, otter, chicken, duck, goose, guinea fowl, pigeon, swan, and turkey. In another example mode, the animal is a human. Alternatively, the method is used in vitro, for example, to eliminate microbial contaminants in a cell culture. In another exemplary embodiment, the compound is a member selected from 3-hydroxypyridine-2-carbonyloxy-bis (3-chloro-4-methylphenyl) -borane (3-hydroxy-piolinate ester of bis (3-chloro-4-methylphenyl) acid. ) borinic acid), 1,3-dihydro-5-fluoro-1-hydroxy-2, 1-benzoxazole, and 5- (4-cyanophenoxy) -1,3-dihydro-1-hydroxy-2, 1-benzoxazole. In another example embodiment, the compound is 3-hydroxypyridine-2-carbonyloxy-bis (3-chloro-4-methylphenyl) -borane. IV. a) Methods comprising fungi or yeasts In an exemplary embodiment, the microorganism is a selected member of a fungus and a yeast. In another example embodiment, the fungus or yeast is a member selected from the species Candida, species Trichophyton, species Microsporium, species Aspergillus, species Cryptococcus, species Blastomyces, species Cocciodiodes, species Histoplasma, species Paracoccidiodes, species Phycomycetes, species Malassezia, species Fusarium, species Epider ophyton, species Scytalidium, species Scopulariopsis, species Alternaria, species Penicillium, species Phialophora, species Rhizopus, species Scedosporium and class Zygomycetes. In another example embodiment, the fungus or yeast is a member selected from Aspergillus fumigatus (A. fumigatus), Blastomyces dermatitidis, Candida Albicans (C. albicans, both strains sensitive and resistant to fluconazole), Candida glabrata (C. glabrata), Candida krusei (C. krusei), Cryptococcus neoformans (C. neoformans), Candida parapsilosis (C. parapsilosis), Candida tropicalis (C. tropicalis), Cocciodiodes immitis, Epidermophyton floccosum (E. floccosum), Fusarium Solani (F. solani), Histoplasma capsulatum, Malassezia fúrfur (M. fúrfur), Malassezia pachydermatis (M. pachydermatis), Malassezia sympodialis (M. sympodialis), Microsporum audouinii (M. audouinii), Microsporum canis (M. canis), Microsporum gypseum (M. gypseum), Paracoccidioides brasiliensis and Phycomycetes spp, Trichophyton mentagrophytes (T. mentagrophytes), Trichophyton rubrum (T. rubrum), Trichophyton tonsurans (T. tonsurans). In another example embodiment, the fungus or yeast is a member selected from Trichophyton concentricum, T. violaceum, T. schoenleinii, T. verrucosum, T. soudanense, Microsporum gypseum, M. equinum, Candida guilliermondii, Malassezia globosa, M. obtuse. , M. restricted, M. slooffiae, and Aspergillus flavus. In another example embodiment, the fungus or yeast is a selected member of dermatophites, Trichophyton, Microsporum, Epidermophyton Aspergillus, Blastomyces, Candida, Coccidioides, Cryptococcus, Hendersonula, Histoplasma, Paecilomyces, Paracoccidiodes, Pneumocystis, Trichosporium and yeast-type fungi. IV. b) Methods Comprising Bacteria In an example embodiment, the microorganism is a bacteria In an exemplary embodiment, the bacterium is a gram-positive bacterium. In another example embodiment, the gram-positive bacterium is a member selected from the species Staphylococcus, species Streptococcus, species Bacillus, species Mycobacterium, species Corynebacterium (species Propionibacterium), species Clostridium, species Actinomyces, species Enterococcus and species Streptomyces. In another example embodiment, the bacterium is a gram-negative bacterium. In another example embodiment, the gram-negative bacterium is a member selected from the species Acinetobacter, species Neisseria, species Pseudomonas, species Brucella, species Agrobacterium, species Bordetella, species Escherichia, species Shigelia, species Yersinia, species Salmonella, species Klebsiella, Enterobacter species, Haemophilus species, Pasteurella species, Streptobacillus species, spirocetal species, Campylobacter species, Vibrio species and Helicobacter species. In another example embodiment, the bacterium is a selected member of Propionibacterium acnes; Staphylococcus aureus; Staphylococcus epidermidis, Staphylococcus saprophyticus; Streptococcus pyrogenes; Streptococcus agalactiae; Streptococcus pneumoniae; Enterococcus faecalis; Enterococcus faecium; Bacillus anthracis; Mycobacterium avium-intracellulare; Mycobacterium tuberculosis, Acinetobacter baumanii; Corynebacterium diphtheria; Clostridium perfringens; Clostridium botulinum; Clostridium tetani; Neisseria gonorrhoeae; Neisseria meningitidis; Pseudomonas aeruginosa; Legionella pneumophila; Escherichia coli; Yersinia pestis; Haemophilus influenzae; Helicobacter pylori; Campylobacter fetus; Campylobacter jejuni; Vibrio cholerae; Vibrio parahemolyticus; Trepomena pallidum; ñctinomyces israelii; Rickettsia prowazekii; Rickettsia rickettsii; Chlamydia trachomatis; Chlamydia psittací; Brucella abortus; Agrobacterium tumefaciens; and Francisella tularensis. In an exemplary embodiment, the bacterium is a selected member of acid fast fasting bacteria, including the Mycobacterium species; bacilli, including the Bacillus species, Corynebacterium species (also Propionibacteria) and Clostridium species; filamentous bacteria, including the species Actinomyces and the species Streptomyces; bacilli, such as the species Pseudomonas, species Brucella, species Agrobacterium, species Bordetella, species Escherichia, species Shigella, species Yersinia, species Salmonella, species Klebsiella, species Enterobacter, species Haemophilus, species Pasteurella, and the species Streptobacillus, spirocetal species, Campylobacter species, Vibrio species and intracellular bacteria including the Rickettsiae species and the Chlamydia species. The compounds of use in the invention are active against a variety of bacterial organisms. They are active both against gram-positive and gram-negative aerobic and anaerobic bacteria, including staphylococci, for example, S. aureus, enterococci, for example, E. faecalis, streptococci, for example, S. pneumoniae, hemophilia, for example, H. influenza.; Moraxela, for example, M. catarrhalis, and Escherichia, for example, E. coli. The compounds of use in the present invention are also active against microbacteria, for example, M. tuberculosis. The compounds of use in the present invention are also active against intercellular microbes, for example, Chlamydia and Rickettsiae. The compounds of use in the present invention are also active against mycoplasma, for example, M. pneumoniae. In addition, the compounds of use in this invention are active against staphylococcal organisms such as S. aureus and staphylococcal coagulase-negative strains such as S. epidermidis that are resistant (including multi-resistant) to other antibacterial agents, eg, β-antibiotics. -lactam such as, for example, methicillin, acrylics, aminoglycosides, and lincosamides. The compounds of use in the present invention are therefore useful in the treatment of RSA, MRCNS and RSE. The compounds of use in the present invention are also active against vancomycin-resistant strains of the strains of E. faecalis and, therefore, of use in the treatment of infections associated with organisms. of VRE. Additionally, the compounds of use in the present invention are useful in the treatment of staphylococcal organisms that are resistant to mupirocin. In another example embodiment, the bacterium is a member selected from the species Actinobacillus, species Porphyromonas, species Tannerella, species Prevotella, species Eubacterium, species Treponema, species Bulleidia, species Mogibacterium, species Slackia, species Campylobacter, species Eikenella, species Peptostreptococcus, species Peptostreptococcus, species Capnocytophata, species Fusobacterium, Porhyromonas species and Bacteroides species. In yet another example embodiment, the bacterium is a selected member of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythensis, Prevotella intermedia, Eubacterium nodatum, Treponema denticola, Bulleidia extructa, Mogibacterium timidum Slackia exigua, Campylobacter rectus, Eikenella corrodens, Peptostreptococcus micros, Peptostreptococcus anaerobius, Capnocytophaga ochracea, Fusobacterium nucleatum, Porphyromonas asaccharolytica and Bacteroides forsythus. In another exemplary embodiment, the compound is a member selected from 3-hydroxypyridine-2-carbonyloxy-bis (3-chloro-4-methylphenyl) -borane (3-hydroxy-piolinate ester of bis (3-chloro-4-methylphenyl) acid. borinic acid), 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole, and 5- (4-cyano-phenoxy) -1,3-dihydro-l-hydroxy-2, 1- benzoxaborol. In another example embodiment, the compound is 3-hydroxypyridine-2-carbonyloxy-bis (3-chloro-4-methylphenyl) -borane. IV. c) Methods Comprising Viruses The compounds of the invention are useful for the treatment of diseases of both animals and humans, comprising viruses. In an exemplary embodiment, the microorganism is a virus. In an exemplary embodiment, the virus is a selected member of hepatitis ABC, human rhinovirus, yellow fever virus, human respiratory coronavirus, severe acute respiratory syndrome (SARS), respiratory syncytial virus, influenza virus, parainfluenza virus 1-4 , human immunodeficiency virus 1 (HIV-1), human immunodeficiency virus 2 (HIV-2), herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), human cytomegalovirus (HCMV) , Varicella zoster virus, Epstein-Barr virus (EBV), poliovirus, coxsackie virus, ecovirus, rubella virus, tropic neuroderma virus, variola virus, papovirus, rabies virus, dengue virus, and West Nile. In another example embodiment, the virus is a selected member of picornaviridae, flaviviridae, coronaviridae, paramyxoviridae, orthomyxoviridae, retroviridae, herpesviridae and hepadnaviridae. In another example embodiment, the virus is a selected member of a virus included in the following table: Table A. Virus Virus Category Human Infections Relevant RNA viruses Picomaviridae Polio Human Hepatitis A Human rhinovirus Togaviridae and Flaviviridae Rubella.- German measles Yellow fever Coronaviridae Respiratory coronavirus (HCV) Severe acute respiratory syndrome Rhabdoviridae (SAR) Lissavirus - rabies Paramyxovirus - mumps Paramyxoviridae Morbillvirus - measles Pneumovirus - respiratory syncytial virus Orthomyxoviridae Influenza AC Bunyavirus - Bunyamwera (BUN) Hantavirus - Hantaan (HTN) Nairevírus - Haemorrhagic fever Bunyaviridae Crimean-Congo (CCHF) Phlebovirus - Fly Fever (SF) Uukuvirus - Uukuniemi (UUK) Rift Valley Fever (RVF) Virus category Human Infections Pertinent Junin - Argentine hemorrhagic fever Arenaviridae Machupo - Bolivian hemorrhagic fever Lassa - Lassa fever LCM - aseptic lymphocytic choriomeningitis Rotovirus Reoviridae Reovirus Orbivirus Human immunodeficiency virus 1 Retroviridae (HIV-1) Human immunodeficiency virus 2 (HIV-2) Simian immunodeficiency virus (SIV) DNA virus Papovaviridae Pediatric virus residing in the kidney Adenoviridae Human respiratory effort and some eye infections deeply Seated parvoviridae Human gastrointestinal effort (Norwalk Virus) Virus Category Human Infections Relevant Herpes simplex virus 1 (HSV-1) Herpesviridae Herpes simplex virus 2 (HSV-2) Human cytomegalovirus (HCMV) Varicella zoster virus (VZV) Epstein-Barr virus (EBV) Virus 6 human herpes (HHV6) Poxiviridae Ortopoxvirus is subgenus for smallpox Hepadnaviridae Hepatitis B virus (HBV) Hepatitis C virus (HCV) IV. d) Methods for Treating Diseases Comprising Parasites The compounds of the invention are useful for the treatment of both animal and human diseases, comprising parasites, including protozoa and helminths. Examples of these parasitic species include, among others, Entamoeba, Leishmania, Toxoplasma, Trichinella and Schistosoma. In an exemplary embodiment, the parasite is a selected member of Plasmodium falciparum, P. vivax, P. ovale P. malariae, P. berghei, Leishmania donovani, L. infantum, L. chagasi, L. mexicana, L. amazonensis, L. venezuelensis, L. tropics, L. major, L. minor, L. aethiopica, L. Banaana braziliensis, L. (V.) guyanensis, L. (V.) panamensis, L. (V.) peruviana, Trypanosoma brucei rhodesiense, T. brucei gambiense, T. cruzi, Giardia intestinalis, G. lambda, Toxoplasma gondii, Entamoeba histolytica, Trichomonas vaginalis, Pneumocystis carinii, and Cryptosporidium parvum. In an exemplary embodiment, the disease caused for the parasite is a selected member of malaria, Chagas disease, Lesihmaniasis, African sleeping sickness (African human trypanosomiasis), giardiasis, toxoplasmosis, amoebiasis and cryptosporidiosis. V. Methods for Treating or Preventing Periodontal Disease In another aspect, the invention provides a method for treating or preventing periodontal disease, or both. The method includes administering to the animal a therapeutically effective amount of a compound of the invention. In an exemplary embodiment, the compound is a member selected from a chlorine-containing compound described herein, sufficient to treat or prevent the disease. In another exemplary embodiment, the compound is a member selected from 3-hydroxypyridine-2-carbonyloxy-bis (3-chloro-4-methylphenyl) -borane (bis (3-chloro-4-methylphenyl) 3-hydroxy-piolinate ester) borinic acid), 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole, and 5- (4-cyanophenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole. In another example embodiment, the compound is 3-hydroxypyridine-2-carbonyloxy-bis (3-chloro-4-methylphenyl) -borane. In another example embodiment, the animal is a member selected from human, cattle, deer, reindeer, goat, honey bee, pig, sheep, horse, cow, bull, dog, guinea pig, gerbil, rabbit, cat, camel, yak, elephant, ostrich, otter, chicken, duck, goose , guinea fowl, pigeon, swan and turkey. In another example mode, the animal is a human. In another example embodiment, the animal is a selected member of a human, cattle, goat, pig, sheep, horse, cow, bull, dog, guinea pig, gerbil, rabbit, cat, chicken and turkey. In another example embodiment, the infection is a selected member of gingivitis, periodontitis or juvenile / acute periodontitis. The invention is further illustrated with the following examples. The examples are not intended to define or limit the scope of the invention. Examples General: melting points were obtained using a Mel-Temp-II melting point apparatus and are not corrected. The 1 H NMR spectra were recorded on the Oxford 300 spectrometer (300 MHz) (Varian). The mass spectra were determined in API 3000 (Applied Biosystems). Purity was determined by HPLC (relative area) using ProStar Model 330 (PDA detector, Varian), Model 210 (pump, Varian), and a BetaBasic-18 4.6 x 150 mm column (Thermo Electron Corporation) with a linear gradient of MeCN from 0 to 100% in 0.01% of H3P0 for 10 minutes followed by 100% MeCN for another 10 minutes at 220 nm. Example 1 Preparation of 3 from 1 1.1 Reduction of Carboxylic Acid To a solution of 1 (23.3 mmol) in anhydrous THF (70 mL) under nitrogen was added dropwise a solution of BH3-THF (1.0 M, 55 mL, 55 mmol) at 0 ° C and the reaction mixture was stirred overnight at room temperature. Then, the mixture was again cooled with an ice bath and MeOH (20 mL) was added dropwise to decompensate the excess BH3. The resulting mixture was stirred until no bubbles were released and then 10% NaOH (10 mL) was added. The mixture was concentrated and the residue was mixed with water (200 mL) and extracted with EtOAc. The residue of the rotary evaporation was purified by flash column chromatography on silica gel to give 20.7 mmol of 3. 1.2 Results The example compounds of structure 3 prepared by the above method are given below. 1.2.a 2-Bromo-5-chlorobenzyl alcohol XR NMR (300 MHz, DMSO-d6); d 7.57 (d, J = 8.7 Hz, 1H), 7.50-7.49 (m, 1H), 7.28-7.24 (m, 1H), 5.59 (t, J = 6.0 Hz, 1H), and 4.46 (d, J = 6.0 Hz, 2H) ppm. 1. 2.b 2-Bromo-5-methoxybenclic alcohol NMR * H (300 MHz, DMSO-d6); d 7.42 (d, J = 8.7 Hz, 1H), 7.09 (d, J = 2.4 Hz, 1H), 6.77 (dd, Ji = 3 Hz, J2 = 3 Hz, 1H), 5.43 (t, J = 5.7 Hz , 1H), 4.44 (d, J = 5.1 Hz, 2H), 3.76 (s, 3H). Example 2 Preparation of 3 from 2 2.1. Reduction of Aldehyde To a solution of 2 (Z0H, 10.7 mmol) in methanol (30 mL) was added sodium borohydride (5.40 mol), and the mixture was stirred at room temperature for 1 hour. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give 9.9 mmol of 3. 2.2 Results The example compounds of structure 3 prepared by the above method are given below. 2.2. a 2-Bromo-5- (4-cyanophenoxy) benzyl alcohol 1 H NMR (300 MHz, CDC13); d (ppm) 2.00 (br s, 1H), 4.75 (s, 2H), 6.88 (dd, J = 8.5, 2.9 Hz, 1H), 7.02 (d, J = 8.8 Hz, 1H), 7.26 (d, J) = 2.6 Hz, 1H), 7.56 (d, J = 8.5 Hz, 1H), 7.62 (d, J = 8.8 Hz, 2H). 2. 2.b Alcohol 2-Bromo-4-. { 4-cyanophenoxy) benzyl NMR XH (300 MHz, DMSO-d6): d 7.83 (d, 2H), 7.58 (d, 1H), 7.39 (d, 1H), 7.18 (dd, 1H), 7.11 (d, 2H) ), 5.48 (t, 1H) and 4.50 (d, 2H) ppm. 2.2.c 5- (4-Cyanophenoxy) -1-Indanol P.f. 50-53 ° C. MS (ESI +): m / z = 252 (M + 1). HPLC: 99.7% purity at 254 nm and 99.0% at 220 nm. X H NMR (300 MHz, DMS0-d 6): d 7.80 (d, 2H), 7.37 (d, 1H), 7.04 (d, 2H), 6.98-6.93 (m, 2H), 5.27 (d, 1H), 5.03 (q, 1H), 2.95-2.85 (m, 1H), 2.75-2.64 (m, 1H), 2.39-2.29 (m, 1H) and 1.85-1.74 (m, 1H) ppm. 2.2.d 2-Bromo-5- (tert-butyldimethylsiloxy) -benzyl alcohol NMR XH (300 MHz, CDC13) d (ppm) 0.20 (s, 6H), 0.98 (s, 9H), 4.67 (brs, 1H), 6.65 (dd, J = 8.2, 2.6 Hz, 1H), 6.98 (d, J = 2.9 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H). Additional examples of compounds that can be produced by this method include 2-bromo-4- (3-cyanophenoxy) benzyl alcohol; 2-bromo-4- (4-chlorophenoxy) benzyl alcohol; 2-bromo-4-phenoxybenzyl alcohol; 2-bromo-5- (3, -dicianophenoxy) benzyl alcohol; 2- (2-bromo-5-fluorophenyl) ethyl alcohol; 2-bromo-5-fluorobenzyl; and l-bromo-2-naphthalenemethanol. Example 3 Preparation of 4 from 3 3.1 Protective Alkylation Compound 3 (20.7 mmol) is dissolved in CH 2 Cl 2 (150 mL) and cooled to 0 ° C with a wire bath. This solution under nitrogen was added in sequence N, N-diisopropyl-ethyl-amine (5.4 mL, 31.02 mmol, 1.5 eq) and methyl chloromethyl ether (2 mL, 25.85 mmol, 1.25 eq). The reaction mixture was stirred overnight at room temperature and washed with water saturated with NaHCO 3 and then water saturated with NaCl. The residue after rotary evaporation was purified by flash column chromatography on silica gel to give 17.6 mmol of 4. 3.2 Results The example compounds of structure 4 prepared by the above method are given below. 3.2.a 2-Bromo-5-chloro-l- (methoxymethoxymethyl) -benzene XH NMR (300 MHz, DMSO-d6): d 7.63 (d, J = 8.7 Hz, 1H), 7.50 (dd, J = 2.4 & amp;; 0.6 Hz, 1H), 7.32 (dd, J = 8.4 &2.4 Hz, 1H), 4.71 (s, 2H), 4.53 (s, 2H) and 3.30 (s, 3H) ppm. 3.2.b 2-Bromo-5-fluoro-1- [1- (methoxymethoxy) ethyl] -benzene NMR * H (300.058 MHz, CDC13) d ppm 1.43 (d, J = 6.5 Hz, 3H), 3.38 (s, 3H), 4.55 (d, J = 6.5 Hz, 1H), 4.63 (d, J = 6.5 Hz, 1H), 5.07 (q, J = 6.5 Hz, 1H), 6.85 (m, 1H), 7.25 (dd, J = 9.7, 2.6 Hz, 1H), 7.46 (dd, J = 8.8, 5.3 Hz, 1H). 3. 2.c 2-Bromo-5-fluoro-1- [2- (methoxymethoxy) ethyl] -benzene XH NMR (300.058 MHz, CDC13) d ppm 3.04 (t, J-6.7 Hz, 2H), 3.31 (s, 3H ), 3.77 (t, J = 6.7 Hz, 2H), 4.62 (s, 2H), 6.82 (td, J = 8.2, 3.2 Hz, 1H), 7.04 (dd, J = 9.4, 2.9 Hz, 1H), 7.48 (dd, J = 8.8, 5.3 Hz, 1H). 3.2.d 2-Bromo-4, 5-difluoro-1- (methoxymethoxymethyl) -benzene 1H-NMR (300.058 MHz, CDC13) d ppm 3.42 (s, 3H), 4.57 (d, J = 1.2 Hz, 2H), 4.76 (s, 2H), 7.3-7.5 (ra, 2H). 3.2.e 2-Bromo-5-cyano-l- (methoxymethoxymethyl) benzene 1N-NMR (300.058 MHz, CDC13) d ppm 3.43 (s, 3H), 4.65 (s, 2H), 4.80 (s, 2H), 7.43 ( dd, J = 8.2, 4.1 Hz, 1H), 7.66 (d, J = 8.2 Hz, 1H), 7.82 (d, J = 4.1 Hz, 1H). 3.2.f 2-Bromo-5-methoxy-l- (methoxymethoxymethyl) benzene NMR ?? (300 MHz, DMSO-d6): d 7.48 (dd, Jx = 1.2 Hz, J2 = 1.2 Hz, 1H), 7.05 (d, J = 2.7 Hz, 1H), 6.83 (dd, Ji = 3 Hz, J2 = 3 Hz, 1H), 4.69 (d, J = 1.2 Hz, 2H), 4.5 (s, 2H), 3.74 (d, J = 1.5 Hz, 3H), 3.32 (d, J = 2.1 Hz, 3H) ppm. 3.2.g 1-Benzyl-1- (2-bromophenyl) -1- (methoxymethoxy) -ethane NMR XH (300 MHz, DMSO-d6): d 7.70-7.67 (m, 1H), 7.25-7.09 (m, 6H ), 6.96-6.93 (m, 2H), 4.61 (d, 1H), 4.48 (d, 1H), 3.36-3.26 (m, 2H), 3.22 (s, 3H) and 1.63 (s, 3H) ppm. 3. 2.h 2-Bromo-6-fluoro-1- (methoxymethoxymethyl) -benzene NMR XH (300 MHz, CDC13) d (ppm) 3.43 (s, 3H), 4.74 (s, 2H), 4.76 (d, J = 2.1 Hz, 2H), 7.05 (t, J = 9.1 Hz, 1H), 7.18 (td, J = 8.2, 5.9 Hz, 1H), 7.40 (d, J = 8.2 Hz, 1H). 3.2.I 2-Bromo-4- (4-cyanophenoxy) -1- (methoxymethoxymethyl) -benzene NMR * H (300 MHz, DMSO-d6): d 7.84 (d, 2H), 7.56 (d, 1H), 7.44 (d, 1H), 7.19-7.12 (m, 3H), 4.69 (s, 2H), 4.56 (s, 2H) and 3.31 (s, 3H) ppm. 3.2. j 2-Bromo-5- (tert-butyldimethylsiloxy) -1- (methoxymethoxymethyl) benzene NMR ?? (300 MHz, CDC13) d (ppm) 0.19 (s, 6H), 0.98 (s, 9H), 3.43 (s, 3H), 4.59 (s, 2H), 4.75 (s, 2H), 6.64 (dd, J = 8.5, 2.9 Hz, 1H), 6 * .98 (d, J = 2.9 Hz, 1H), 7.36 (d, J = 8.5 Hz, 1H). 3.2. k 2-Bromo-5- (2-cyanophenoxy) -1- (methoxymethoxymethyl) -benzene 1N-NMR (300 MHz, CDCl 3) d (ppm) 3.41 (s, 3 H), 4.64 (s, 2 H), 4.76 (s, 2H), 6.8-6.9 (m, 2H), 7.16 (td, J = 7.6, 0.9 Hz, 1H), 7.28 (d, J = 2.9 Hz, 1H), 7.49 (ddd, J = 8.8, 7.6, 1.8 Hz , 1H), 7.56 (d, J = 8.5 Hz, 1H), 7.67 (dd, J = 7.9, 1.8 Hz, 1H). 3.2.1 2-Bromo-5-phenoxy-1- (methoxymethoxymethyl) -benzene lti NMR (300 MHz, CDC13) d (ppm) 3.40 (s, 3H), 4.62 (s, 2H), 4.74 (s, 2H), 6.80 (dd, J = 8.8, 2.9 hz, 1H), 7.01 (d, J = 8.5 Hz, 2H), 7.12 (t, J = 7.9 Hz, 1H) , 7.19 (d, J = 2.9 hz, 1H), 7.35 (t, J = 7.6 Hz, 2H), 7.48 (d, J = 8.5 Hz, 1H). Additional examples of compounds that can be produced by this method include 2-bromo-l- (methoxymethoxymethyl) benzene; 2-bromo-5-methyl-l- (methoxymethoxymethyl) benzene; 2-bromo-5- (methoxymethoxymethyl) -1- (methoxymethoxymethyl) benzene; 2-bromo-5-fluoro-1- (methoxymethoxymethyl) benzene; l-bromo-2- (methoxymethoxymethyl) naphthalene; 2-bromo-4-fluoro-1- (methoxymethoxymethyl) benzene; 2-phenyl-1- (2-bromophenyl) -1- (methoxymethoxy) ethane; 2-bromo-5- (4-cyanophenoxy) -1- (methoxymethoxymethyl) benzene; 2-bromo- - (3-cyanophenoxy) -1- (methoxymethoxymethyl) benzene; 2-bromo-4- (4-chlorophenoxy) -1- (methoxymethoxymethyl) benzene; 2-bromo-4-phenoxy-1- (methoxymethoxymethyl) benzene; 2-bromo-5- (3,4-dicyanophenoxy) -1- (methoxymethoxymethyl) benzene. Example 4 Preparation of I from 4 by 5 4.1 Metalation and boronylation To a solution of 4 (17.3 mmol) in anhydrous THF (80 mL) at -78 ° C under nitrogen was added dropwise ter-BuLi or n-BuLi (11.7 mL) and the solution became brown. Then, B (OMe) 3 (1.93 mL, 17.3 mmol) was injected in a portion and the cooling bath was removed. The mixture was gradually heated with stirring for 30 minutes and then stirred with a water bath for 2 hours. After the addition of 6N HC1 (6 mL), the mixture was stirred overnight at room temperature and approximately 50% hydrolysis occurred as shown by TLC analysis. The solution was rotary evaporated and the residue was dissolved in MeOH (50 mL) and 6N HCl (4 mL). The solution was refluxed for 1 hour and the hydrolysis was completed as indicated by TLC analysis. Rotary evaporation gave a residue that was dissolved in EtOAc, washed with water, dried and then evaporated. The crude product was purified by flash column chromatography on silica gel to provide a solid with 80% purity. The solid was further purified by washing with hexane to give 7.2 mmol of I. 4.2 Results The analytical data for the example compounds of structure I are given below. 4.2.a 5-Chloro-l, 3-dihydro-l-hydroxy-2, 1-benzoxazole 5-chlorobenzo [c] [1, 2] oxaborol-1 (3H) -ol (Cl) P.f. 142-150 ° C. MS (ESI): m / z = 169 (M + l, positive) and 167 (M-l, negative). HPLC (220 nm): 99% purity. X H NMR (300 MHz, DMSO-d 6): d 9.30 (s, 1H), 7.71 (d, J = 7.8 Hz, 1H), 7.49 (s, 1H), 7.38 (d, J = 7.8 Hz, 1H) and 4.96 (s, 2H) ppm. 4. 2.b 1, 3-Dihydro-l-hydroxy-2, 1-benzoxazole benzo [c] [1, 2] oxaborol-1 (3H) -ol (C2) P.f. 83-86 ° C. S (ESI): m / z = 135 (M + l, positive) and 133 (M-l, negative). HPLC (220 nm): 95.4% purity. X H NMR (300 MHz, DMSO-d 6): d 9.14 (s, 1 H), 7.71 (d, J = 7.2 Hz, 1 H), 7.45 (t, J = 7.5 Hz, 1 H), 7.38 (d, J = 7.5 Hz, 1H), 7.32 (t, J = 7.1 Hz, 1H) and 4.97 (s, 2H) ppm. 4.2.C 5-Chloro-3-methylbenzo [c] [1, 2] oxaborol-1 (3H) -ol (C3) NMR-NMR (300 MHz, DMSO-d6) d ppm 1.37 (d, J = 6.4 Hz, 3H), 5.17 (q, J = 6.4 Hz, 1 H), 7.14 (m, 1H), 7.25 (dd, J = 9.7, 2.3 Hz, 1H), 7.70 (dd, J = 8.2, 5.9 Hz, 1H) , 9.14 (s, 1H). 4.2.d 6-Fluoro-l-hydroxy-l, 2,3, 4-tetrahydro-2, 1-benzoxaborine 6-fluoro-3,4-dihydrobenzo [c] [1,2] oxaborinin-l-ol (C4) 1 H NMR (300 MHz, DMSO-d 6) d ppm 2.86 (t, J = 5.9 Hz, 2H), 4.04 (t, J = 5.9 Hz, 2H), 7.0-7.1 (m, 2H), 7.69 ( dd, J = 8.2, 7.2 Hz, 1H), 8.47 (s, 1H). 4.2.e 5,6-Difluoro-1,3-dihydro-l-hydroxy-2, 1-benzoxazole-5,6-difluorobenzo [c] [1, 2] oxaborol-1 (3H) -ol (C5) NMR XH (300 MHz, DMSO-d6) d ppm 4.94 (s, 2H), 7.50 (dd, J = 10.7, 6.8 Hz, 1H), 7.62 (dd, J = 9.7, 8.2 Hz, «lH), 9.34 (s, 1 HOUR) . 4. 2.f 5-Cyano-l, 3-dihydro-l-hydroxy-2, 1-benzoxazole 1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-5-carbonitrile (C6) 1H-NMR ( 300 MHz, D SO-d6) d ppm 5.03 (s, 2H), 7.76 (d, J = 8.2 Hz, 1H), 7.89 (d, J = 8.2 Hz, 1H), 7.90 (s, 1H), 9. 53 (s, 1H). 4.2.g 1, 3-Dihydro-l-hydroxy-5-methoxy-2, 1-benzoxazole 5-methoxybenzo [c] [1, 2] oxaborol-1 (3H) -ol (C7) P.f. 102-104 ° C. MS ESI: m / z = 165.3 (+ l) and 162.9 (M-l). X H NMR (300 MHz, DMSO-d 6): d 8.95 (s, 1 H), 7.60 (d, J = 8. 1 Hz, 1H), 6.94 (s, 1H), 6.88 (d, J = 8.1 Hz, 1H), 4.91 (s, 2H), 3.77 (s, 3 H) ppm. 4.2.h 1, 3-Dihydro-l-hydroxy-5-methyl-2, 1-benzoxazole 5-methylbenzo [c] [1, 2] oxaborol-1 (3H) -ol (C8) P.f. 124-128 ° C. MS ESI: m / z = 148.9 (M + l) and 146.9 (M-l). R N 1 H (300 MHz, D S0-d 6): d 9.05 (s, 1H), 7.58 (d, J = 7. 2 Hz, 1H), 7.18 (s, 1H), 7.13 (d, J = 7.2 Hz, 2H), 4.91 (s, 2H), 2.33 (s, 3H) ppm. 4.2. i 1, 3-Dihydro-l-hydroxy-5-hydroxymethyl-2, 1-benzoxazole 5- (hydroxymethyl) benzo [c] [1, 2] oxaborol-1 (3H) -ol (C9) MS: m / z = 163 (Ml, ESI-). 1N NMR (300 MHz, DMSO-de): d 9.08 (s, 1H), 7.64 (d, 1H), 7.33 (s, 1H), 7. 27 (d, 1H), 5.23 (t, 1H), 4.96 (s, 2H), 4.53 (d, 2H) ppm. 4. 2. 1, 3-Dihydro-5-fluoro-l-hydroxy-2, 1-benzoxa-borol 5-fluorobenzo [c] [1, 2] oxaborol-1 (3H) -ol (CIO) • P.f. 110-114 ° C. MS ESI: m / z = 150.9 (M-l). 1N-NMR (300 MHz, DMSO-d6): d 9.20 (s, 1H), 7.73 (dd, Ji = 6 Hz, J2 = 6 Hz, 1H), 7.21 (m, 1H), 7.14 (m, 1H), 4.95 (s, 2H) ppm. 4.2. k 1, 3-Dihydro-2-oxa-l-cyclopenta [ot] naphthalene naphtho [l, 2-c] [1, 2] oxaborol-1 (3H) -ol (CU) M.f. 139-143 ° C. MS ESI: m / z = 184.9 (M + l). 1 H-NMR (300 MHz, DMSO-d 6): d 9.21 (s, 1H), 8.28 (dd, Ji = 6.9 Hz, J2 = 0.6 Hz, 1H), 7.99 (d, J = 8.1 Hz, 1H), 7.95 ( d, J = 7.5 Hz, 1H), 7.59-7.47 (m, 3H), 5.09 (s, 2H) ppm. 4.2. m 1, 3-Dihydro-6-fluoro-l-hydroxy-2, 1-benzoxazole-6-fluorobenzo [c] [1, 2] oxaborol-1 (3H) -ol (C13) P.f. 110-117.5 ° C. MS (ESI): m / z = 151 (M-l, negative). HPLC (220 nm): 100% purity. X H NMR (300 MHz, DMSO-de): d 9.29 (s, 1H), 7.46-7.41 (m, 2H), 7.29 (td, 1H) and 4.95 (s, 2H) ppm. 4.2.n 3-Benzyl-l, 3-dihydro-l-hydroxy-3-methyl-2, 1-benzoxazole 3-benzyl-3-methylbenzo [c] [1, 2] oxaborol-1 (3H) -ol (C14) MS (ESI): m / z = 239 (M + l, positive). HPLC: 99.5% purity at 220 nm and 95.9% at 254 nm. X H NMR (300 MHz, DMSO-d 6): d 8.89 (s, 1H), 7.49-7.40 (m, 3H), 7.25-7.19 (m, 1H), 7.09-7.05 (m, 3H), 6.96-6.94 (m, 2H), 3.10 (d, 1H), 3.00 (d, 1H) and 1.44 (s, 3H) ppm. 4.2.0 3-Benzyl-l, 3-dihydro-l-hydroxy-2, 1-benzoxazole 3-benzylbenzo [c] [1, 2] oxaborol-1 (3H) -ol (C15) MS (ESI +): m / z = 225 (M + l). HPLC: 93.4% purity at 220 nm. X H NMR (300 MHz, DMSO-d 6): d 9.08 (s, 1H), 7.63 (dd, 1H), 7.43 (t, 1H), 7.35-7.14 (m, 7H), 5.38 (dd, 1H), 3.21 (dd, 1H) and 2.77 (dd, 1H) ppm. 4.2.p 1, 3-Dihydro-4-fluoro-l-hydroxy-2, 1-benzoxazole 4-fluorobenzo [c] [1, 2] oxaborol-1 (3H) -ol (C16) NMR XH (300 MHz, DMSO-d6) d (ppm) 5.06 (s, 2H), 7.26 (ddd, J = 9.7, 7.9, 0.6 Hz, 1H), 7.40 (td, J = 8.2, 4.7 Hz, 1H), 7.55 (d, J = 7.0 Hz, 1H), 9.41 (s, 1H). 4.2.q 5- (4-Cyanophenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole 4- (1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-5- iloxy) benzonitrile (C17) 1 H NMR (300 MHz, DMS0-d6) d ppm 4.95 (s, 2H), 7.08 (dd, J = 7.9, 2.1 Hz, 1H), 7.14 (d, J = 8.8 Hz, 1H), 7.15 (d, J = 2.1 Hz, 1H), 7.78 (d, J = 7.9 Hz, 1H), 7.85 (d, J = 9.1 Hz, 2H), 9.22 (s, 1H). 4.2.r 6- (4-Cyanophenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole 4- (1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-6- iloxy) benzonitrile (C18) Pf 148-151 ° C. MS: m / z = 252 (M + l) (ESI +) and m / z = 250 (M-l) (ESI-). HPLC: 100% purity at 254 nm and 98.7% at 220 nm. X H NMR (300 MHz, DMSO-d 6): d 9.26 (s, 1 H), 7.82 (d, 2 H), 7.50 (d, 1 H), 7.39 (d, 1 H), 7.26 (dd, 1 H), 7.08 (d , 2H) and 4.99 (s, 2H) ppm 4.2.s 6- (3-Cyanophenoxy) -1, 3-dihydro-l-hydroxy-2, 1-benzoxazole 3- (1-hydroxy-l, 3-dihydrobenzo [ c] [1,2] oxaborol-6-yloxy) benzonitrile (C19) Pf 146-149 ° C. MS: m / z = 252 (M + 1) (ESI +) and m / z = 250 (M-1) (ESI-). HPLC: 100% purity at 254 nm and 97.9% at 220 nm. 1 H NMR (300 MHz, DMSO-d 6): d 9.21 (s, 1H), 7.60-7.54 (m, 2H), 7.50-7.45 (m, 2H), 7.34-7.30 (m, 2H), 7.23 (dd, 1H) and 4.98 (s, 2H) ppm. 4.2.t 6- (4-Chlorophenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole 6- (4-chlorophenoxy) benzo [c] [1,2] oxaborol-1 (3H) -ol (C20) P.f. 119-130 ° C. MS: m / z = 261 (M + 1) (ESI +) and m / z = 259 (M-1) (ESI-). HPLC: 100% purity at 254 nm and 98.9% at 220 nm. 1 H NMR (300 MHz, DMSO-d 6): d 9.18 (s, 1H), 7.45-7.41 (m, 3H), 7.29 (d, 1H), 7.19 (dd, 1H), 7.01 (d, 2H) and 4.96 (s, 2H) ppm. 4.2.u 6-Phenoxy-13-dihydro-l-hydroxy-2, 1-benzoxazole 6-phenoxybenzo [c] [1, 2] oxaborol-1 (3H) -ol (C21) P.f. 95-99 ° C. MS: m / z = 227 (M + l) (ESI +) and m / z = 225 (M-l) (ESI-). HPLC: 100% purity at 254 nm and 98.4% at 220 nm.

X H NMR (300 MHz, DMSO-d 6): d 9.17 (s, 1 H), 7.43-7.35 (m, 3 H), 7.28 (s, 1 H), 7.19-7.09 (m, 2 H), 6.99 (d, 2 H) and 4.96 (s, 2H) ppm. 4.2.v 5- (4-Cyanobenzyloxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole 4- ((1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-5 -iloxy) methyl) benzonitrile (C22) NMR XH (300 MHz, D SO-d6) d (ppm) 4.90 (s, 2H), 5.25 (s, 2H), 6.98 (dd, J = 7.9, 2.1 Hz, 1H ), 7.03 (d, J = 1.8 Hz, 1H), 7.62 (d, J = 7.9 Hz, 1H), 7.64 (d, J = 8.5 Hz, 2H), 7.86 (d, J = 8.5 Hz, 1H), 9.01 (s, 1H). 4.2.w 5- (2-Cyanophenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole 2- (1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-5- iloxy) benzonitrile (C23) NMR XH (300 MHz, DMSO-d6) d (ppm) 4.95 (s, 2H), 7.0-2.2 (m, 3H), 7.32 (td, J = 7.6, 1.2 Hz, 1H), 7.68 (ddd, J = 9. 1, 7.6, 1.8 Hz, 1H), 7.77 (d, J = 7.9 Hz, 1H), 7.91 (dd, J = 7.9, 1.8 Hz, 1H). 4.2. x 5-Phenoxy-1, 3-dihydro-l-hydroxy-2, 1-benzoxazole 5-phenoxybenzo [c] [1, 2] oxaborol-1 (3H) -ol (C24) XH NMR (300 MHz, DMSO- d6) d (ppm) 4.91 (s, 2H), 6.94 (s, 1H), 6.96 (d, J = 8.8 Hz, 1H), 7.05 (d, J = 7.6 Hz, 2H), 7.17 (t, J = 7.3 Hz, 1H), 7.41 (t, J = 7.3 Hz, 2H), 7.70 (d, J = 8.5 Hz, 1H), 9.11 (s, 1H). 4. 2. and 5- [4- (N, N-Diethylcarbamoyl) phenoxy-1,3-dihydro-l-hydroxy-2-, 1-benzoxazole N, N-diethyl-4- (1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-5-yloxy) benzamide (C25) 1 H-NMR (300 MHz, DMSO-d6) d (ppm) 1.08 (br s, 6H), 3.1-3.5 (m, 4H), 4.93 (s, 2H), 7.0-7.1 (ra, 4H), 7.37 (d, J = 8. 5 Hz, 2H), 7.73 (d, J = 7.9 Hz, 1H), 9.15 (s, 1H). 4.2. z 1, 3-Dihydro-l-hydroxy-5- [4- (morpholinocarbonyl) phenoxy-2, 1-benzoxazole (4- (1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-5 -iloxy) phenyl) (morpholino) methanone (C26) 1 H-NMR (300 MHz, DMSO-d6) d (ppm) 3.3-3.7 (m, 8H), 4.93 (s, 2H), 7.0-7.1 (m, 4H) , 7.44 (d, J = 8.8 Hz, 2H), 7.73 (d, J = 7.9 Hz, 1H), 9.16 (s, 1H). 4.2.aa 5- (3,4-Dicyamphenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole 4- (1-hydroxy-1,3-dihydrobenzo [c] [1,2] oxaborol- 5-yloxy) phthalonitrile (C27) 1 H-NMR (300 MHz, DMSO-d 6) d (ppm) 4.97 (s, 2 H), 7.13 (dd, J = 7.9, 2.1 Hz, 1 H), 7.21 (d, J = 1.5 Hz, 1H), 7.43 (dd, J = 8.8, 2.6 Hz, 1H), 7.81 (d, J = 7.9 Hz, 1H), 7.82 (d, J = 2. 6 Hz, 1H), 8.11 (d, J = 8.5 Hz, 1H), 9.26 (s, 1H). 4.2. ab 6-Phenylthio-l, 3-dihydro-l-hydroxy-2, 1-benzoxazole 6- (phenylthio) benzo [c] [1,2] oxaborol-1 (3H) -ol (C28) P.f. 121-124 ° C. MS: m / z = 243 (M + 1) (ESI +) and m / z = 241 (M-1) (ESI-). HPLC: 99.6% purity at 254 nm and 99.6% at 220 nm. X H NMR (300 MHz, DMSO-d 6): d 9.25 (s, 1H), 7.72 (dd, 1H), 7.48 (dd, 1H), 7.43 (dd, 1H), 7.37-7.31 (m, 2H), 7.29 -7.23 (m, 3H), and 4.98 (s, 2H) ppm. 4.2.ac 6- (4-tri-fluoroproethoxyphenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole 6- (4- (trifluoromethoxy) phenoxy) benzo [c] [1,2] oxaborol-1 ( 3H) -ol (C29) Pf 97-101 ° C. MS: m / z = 311 (M + 1) (ESI +) and m / z = 309 (M-1) (ESI-). HPLC: 100% purity at 254 nm and 100% at 220 nm. X H NMR (300 MHz, DMSO-d 6): d 9.20 (s, 1H), 7.45 (d, 1H), 7.37 (d, 2H), 7.33 (d, 1H), 7.21 (dd, 1H), 7.08 (d , 2H), and 4.97 (s, 2H) ppm. 4.2. ad 5- (N-Methyl-N-phenylsulfonylamino) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole N- (1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol- 5-yl) -N-met i lbencenosul fonamide (C30) Pf 85-95 ° C. MS: m / z = 304 (M + 1) (ESI +) and m / z = 302 (M-1) (ESI-). HPLC: 96.6% purity at 254 nm and 89.8% at 220 nm. X H NMR (300 MHz, DMSO-d 6): d 9.23 (s, 1 H), 7.72-7.63 (m, 2 H), 7.56 (t ", 2 H), 7.50 (d, 2 H), 7.16 (s, 1 H), 7.03 (d, 1H), 4.91 (s, 2H) and 3.14 (s, 3H) ppm. 4. 2.ae 6- (-methoxyphenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole 6- (4-methoxyphenoxy) benzo [c] [1,2] oxaborol-1 (3H) -ol (C31) P.f. 126-129 ° C. MS: m / z = 257 (M + 1) (ESI +) and m / z = 255 (M-1) (ESI-). HPLC: 98.4% purity at 254 nm and 98.4% at 220 nm. 1 H NMR (300 MHz, DMSO-d 6): d 9.14 (s, 1 H), 7.36 (d, 1 H), 7.19 (s, ΔH), 7.12 (d, 1 H), 6.98 (d, 2 H), 6.95 (d , 2H), 4.93 (s, 2H) and 3.73 (s, 3H) ppm. 4.-2.af 6- (4-Methoxyphenylthio) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole 6- (4-methoxyphenylthio) benzo [c] [1,2] oxaborol-1 (3H ) -ol (C32) P.f. 95-100 ° C. MS: m / z = 272 (M +), 273 (M + 1) (ESI +) and m / z = 271 (M-1) (ESI-). HPLC: 100% purity at 254 nm and 99.2% at 220 nm. RMN ?? (300 MHz, DMSO-d6): d 9.20 (s, 1H), 7.51 (d, 1H), 7.39-7.28 (m, 4H), 6.98 (d, 2H), 4.93 (s, 2H) and 3.76 (s) , 3H) ppm. 4.2. ag 6- (4-Methoxyphenylsulfonyl) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole 6- (4-methoxyphenylsulfonyl) benzo [c] [1,2] oxaborol-1 (3H) -ol (C33 ) Pf 180-192 ° C. MS: m / z = 305 (M + 1) (ESI +) and m / z = 303 (M-1) (ESI-). HPLC: 96.8% purity at 254 nm and 95.5% at 220 nm. X H NMR (300 MHz, DMSO-d 6): d 9.46 (s, 1 H), 8.28 (s, 1 H), 7.99 (d, 1 H), 7.85 (d, 2 H), 7.61 (d, 1 H), 7.11 (d , 2H), 5.02 (s, 2H) and 3.80 (s, 3H) ppm. 4.2.ah 6- (4-Methoxyphenylsulfinyl) -1, 3-dihydro-l-hydroxy-2, 1-benzoxazole 6- (4-methoxyphenylsulfinyl) benzo [c] [1,2] oxaborol-1 (3H) -ol (C34) NMR XH (300 Hz, DMSO-d6): d 9.37 (s, 1H), 8.02 (d, 1H), 7.71 (dd, 1H), 7.59 (d, 2H), 7.53 (d, 1H), 7.07 (d, 2H), 5.00 (s, 2H) and 3.76 (s, 3H) ppm. 4.2.ai 5-Trifluoromethyl-1,3-dihydro-l-hydroxy-2, 1-benzoxazole 5- (trifluoromethyl) benzo [c] [1, 2] oxaborol-1 (3H) -ol (C35) P.f. 113-118 ° C. MS: m / z = 203 (M + 1) (ESI +) and m / z = 201 (M-1) (ESI-). HPLC: 100% purity at 254 nm and 100% at 220 nm. X H NMR (300 MHz, DMSO-d 6): d 9.48 (s, 1H), 7.92 (d, 1H), 7.78 (s, 1H), 7.67 (d, 1H) and 5.06 (s, 2H) ppm. 4.2.aj 4- (4-Cyanophenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole 4- (1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-4- iloxy) benzonitrile (C36) For the coupling reaction between 4-fluorobenzonitrile and substituted phenol to give the starting material 2 see Igarashi, S.; et al. Chemical & Pharmaceutical Bulletin (2000), 48 (11), 1689-1697. NMR XH (300 Hz, DMSO-d6) (ppm) 4.84 (s, 2H), 7.08 (d, J = 8.2 Hz, 2H), 7.18 (d, J = 7.9 Hz, 1H), 7.45 (t, J = 7.3 Hz, 1H), 7.63 (d, J = 7.3 Hz, 1H), 7.82 (d, J = 8.5 Hz, 2H). 4.2.ak 5- (3-Cyanophenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole 3- (1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-5- iloxy) benzonitrile (C37) For coupling between 3-fluorobenzonitrile and substituted phenol to give starting material 2: Li, F. et al., Organic Letters (2003), 5 (12), 2169-2171. X H NMR (300 MHz, DMSO-d 6) (ppm) 4.93 (s, 2 H), 7.0- 7.1 (m, 2 H), 7.3-7.4 (m, 1 H), 7.5-7.7 (m, 3H), 7.75 (d, J = 8.2 Hz, 1H). 4.2. 5- (4-Carboxyphenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole 4- (1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-5-yloxy) benzoic acid (C38) To a solution of 5- (4-cyanophenoxy) -l-hydroxy-2, 1-benzoxazole obtained in C17 (430 mg, 1.71 mmol) in ethanol (10 mL) was added 6 mol / L of sodium hydroxide. (2 mL), and the mixture was refluxed for 3 hours. Hydrochloric acid (6 mol / L, 3 mL) was added and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and dried in anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate) followed by trituration with diisopropyl ether to give the objective compound (37 mg, 8%). NMR XH (300 MHz, DMS0-d6) d (ppm) 4.94 (s, 2H), 7.0-7.1 (m, 4H), 7.76 (d, J = 7.9 Hz, 1H), 7.94 (d, J = 8.8 Hz , 2H), 9.19 (s, 1H), 12.8 (br s, 1H). 4.2. am 1-Hydroxy-1,3-dihydro-5- [4- (tetrazol-1-yl) phenoxy] -2,1-benzoxazole 5- (4- (lH-tetrazol-5-yl) phenoxy) benzo [c] [1,2] oxaborol-1 (3H) -ol (C39) A mixture of 5- (4-cyanophenoxy) -l-hydroxy-2, 1-benzoxazole (200 mg, 0.797 mmol), sodium azide (103 mg, 1.59 mmol), and ammonium chloride (85 mg, 1.6 mmol) in N, N-dimethylformamide (5 mL) was stirred at 80 ° C for two days. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate) followed by trituration with ethyl acetate to give the objective compound (55 mg, 23%). NMR XH (300 MHz, DMSO-d6) d (ppm) 4.95 (s, 2H), 7.0- 7. 1 (m, 2H), 7.23 (d, J = 8.8 Hz, 2H), 7.76 (d, J = 7.9 Hz, 1H), 8.05 (d, J = 8.5 Hz, 2H), 9.18 (br s, 1H) . Example 5 Preparation of I from 2 by 6 5.1 Catalytic boronilation, reduction and cyclization A mixture of 2 (10.0 mmol), bis (pinacolato) diboro (2.79 g, 11.0 mmol), PdCl2 (dppf) (250 mg, 3% in mol), and potassium acetate (2.94 g, 30.0 mmol) in 1,4-dioxane (40 mL) was stirred at 80 ° C overnight. Water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. The crude product was dissolved in tetrahydrofuran (80 mL), and then sodium periodate (5.56 g, 26.0 mmol) was added. After stirring at room temperature for 30 minutes, 2N HC1 (10 mL) was added, and the mixture was stirred at room temperature overnight. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was treated with ether to give 6.3 mmol of the corresponding boronic acid. To the solution of the boronic acid obtained (0.595 mmol) in methanol (5 mL) was added sodium borohydride (11 mg, 0.30 mmol), and the mixture was stirred at room temperature for 1 hour. Water was added, and the mixture was extracted with ethyl acetate. ethyl. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography to give 0.217 mmol of I. 5.2 Results The analytical data for the example compounds of structure I are given below. 5.2.a 1, 3-Dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole (CIO) The analytical data for this compound are listed in 4.2. j. Example 6 Preparation of I from 3 6.1 Boronylation in a Boil and Cyclization To a solution of 3 (4.88 mmol) and triisopropyl-borate (1.35 mL, 5.86 mmol) in tetrahydrofuran (10 mL) was added n-butylium (1.6 mol). / L in hexanes, 6.7 mL, 10.7 mmol) dropwise for 15 min at -78 ° C under nitrogen atmosphere, and the mixture was stirred for 2 hours while allowing to warm to room temperature. The reaction was quenched with 2 N HC1, and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography and treated with pentane to give 0.41 mmol of I. 6. 2 Results Analytical data for exemplary compounds of structure I 6.2.a 1, 3-Dihydro-5-fluoro-l-hydroxy-2 are provided below, 1-benzoxazole (CIO) The analytical data for this compound are listed in 4.2. j. Example 7 Preparation of I from 3 7.1 Boronylization in a Marmite and Cyclization with Distillation To a solution of 3 (4.88 mmol) in toluene (20 mL) was added triisopropyl borate (2.2 mL, 9.8 mmol), and the mixture was mixed. heated at reflux for 1 hour. The solvent, the isopropyl alcohol generated and the excess triisopropyl borate were removed under reduced pressure. The residue was dissolved in tetrahydrofuran (10 mL) and cooled to -78 ° C. N-Butyllithium (3.2 mL, was added dropwise over 10 minutes. . 1 mmol), and the mixture was stirred for 1 hour while allowing it to warm to room temperature. The reaction was quenched with 2 N HC1, and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography to give 1.54 mmol of I. 7.2 Results Analytical data are provided below for Example compounds of structure I. 7.2.a 1, 3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole (CIO) The analytical data for this compound are listed in 4.2. j. Example 8 Preparation of 8 from 7 8.1 Bromination To a solution of 7 (49.5 mmol) in carbon tetrachloride (200 mL) were added N-bromosuccinimide (8.81 g, 49.5) and N, N-azoisobutylonitrile (414 mg, 5%). % in mol) and the mixture was heated to reflux for 3 hours. Water was added, and the mixture was extracted with chloroform. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give intermediate 8 brominated with methyl, crude. Example 9 Preparation of 3 from 8 9.1 Hydroxylation To crude 8 (49.5 mmol) were added dimethylformamide (150 mL) and acetate partner (20.5 g, 250 mmol), and the mixture was stirred at 80 ° C overnight. Water was added, and the mixture was extracted with ether. The organic layer was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. To the residue was added methanol (150 mL) and sodium hydroxide 1 N (50 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated to approximately one third of the volume under reduced pressure. Water and hydrochloric acid were added, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and water, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography followed by trituration with dichloromethane to give 21.8 mmol of 3. 9.2 Results Example compounds of structure 3 prepared by the method are given below. previous. 9.2.a 2-Bromo-5-cyanobenzyl alcohol XH NMR (300 Hz, SO-D6 D) d ppm 4.51 (d, J = 5.9 Hz, 2H), 5.67 (t, J = 5.6 Hz, 1H), 7.67 ( dd, J = 8.2, 2.0 Hz, 1H), 7.80 (s, J = 8.2 Hz, 1H), 7.83 (d, J - 2.0 Hz, 1H). Additional examples of compounds that can be produced by this method include 2-bromo-5- (4-cyanophenoxy) benzyl alcohol. Example 10 Preparation of 9 from 2 10.1 Reaction A mixture of 2 (20.0 mmol), (methoxymethyl) triphenylphosphonium chloride (8.49 g, 24.0 mmol), and potassium tert-butoxide (2.83 g, 24.0 mol) in N, -dimethylformamide (50 mL) was stirred at room temperature overnight. The reaction was quenched with HC1 6 N, and the mixture was extracted with ethyl acetate. The organic layer was washed with water (x2) and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. To the residue were added tetrahydrofuran (60 mL) and HC1 6 N, and the mixture was heated to reflux for 8 hours. Water was added, and the mixture was extracted with ether. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give 16.6 mmol of 9. EXAMPLE 11 Preparation method of step 13 11.1 Reaction A solution of I in an appropriate alcohol solvent (R1-OH) was refluxed under nitrogen atmosphere and then Distilled to remove the alcohol to give the corresponding ester. Example 12 Preparation of Ib from 12.1 Reaction To a solution of the in toluene was added amino alcohol and the precipitated solid was collected to give Ib. 12. 2 Results It was dissolved (500 mg, 3.3 mmol) in toluene (37 mL) at 80 ° C and ethanolamine (0.20 mL, 3.3 mmol) was added. Mix cooled to room temperature, then bath with ice and filtered to give C40 as a white powder (600.5 mg, 94%). 12.2a Ethanolamine adduct of 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole (C40) XH NMR (300 MHz, DMSO-d6) d (ppm) 2.88 (t, J = 6.2 Hz , 2H), 3.75 (t, J = 6.3 Hz, 2H), 4.66 (s, 2H), 5.77 (br, 2H), 6.85-6.91 (m, 2H), 7.31 (td, J = 7.2, 1.2 Hz, 1 HOUR) . Example 13 Preparation of pyridinyl oxavalosses 14a. Metalation and Boronylation To a solution of 3-bromo-4-hydroxymethylpyridine (10.7 mmol) and B (OMe) 3 (2.73 mL, 11.9 mmol) in anhydrous THF (20 mL) at -78 ° C under nitrogen was added dropwise n-BuLi (13.6 mL, 21.8 mmol). The cooling bath was then removed. The mixture was gradually heated with stirring for 30 minutes and then stirred with a water bath for 2 hours. Brine was then added and the pH adjusted to 7 using 6N HC1. The mixture was washed with THF (x 2) and the aqueous layer (containing the product) was evaporated to dryness. The residue was washed with THF and the product was extracted into ethanol (x2). The ethanol was removed in vacuo, water was added to the residue and it was removed in vacuo. Toluene was added and removed in vacuo. The resulting residue was triturated with diethyl ether and the product was collected by filtration to give C12. 14b. 7-Hydroxy-2, 1-oxaborolane [5,4-c] pyridine [[1,2] oxaborol [3, 4-c] pyridin-l (3 H) -ol] (C12) NMR: H (300 MHz, DMSO-d6) d ppm 5.00 (s, 2H), (d, J = 5.0 Hz, 1H), 8.57 (d, J = 5.3 Hz, 1H), 8.91 (s, 1H), 9.57 (s, 1H). ESIs m / z 134 (M-H) ~, C6H6BN02 = 135. EXAMPLE 14 Cyclic borinic esters Additional compounds can be produced by the methods described herein. In choosing the appropriate starting material such as 1 or 3, Examples 1-7 can be used to formulate the following compounds. Where available, the melting point characterization for these compounds is provided. 14. Results Analytical data are given below for exemplary compounds of structure I. 1 to 2- (1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-5-yloxy) ethyl acetate ( C41) P.f. 134-137 ° C. Starting material example: 2- (4-bromo-3- (hydroxymethyl) phenoxy) ethyl acetate. 14b 2- (1-Hydroxy-l, 3-dihydrobenzo [c] [1, 2] oxaborol-5-yloxy) acetic acid (C42) P.f. 163-166 ° C. Starting material example: 2- (4-bromo-3- (hydroxymethyl) phenoxy) ethyl acetate. The title compound was obtained after saponification of the corresponding ester. 14c 6- (thiophen-2-ylthio) benzo [c] [1, 2] oxaborol-1 (3H) -ol (C43) P.f. 99-104 ° C. Starting material example: (2-bromo-4- (thiophen-2-ylthio) phenyl) methanol. 14d 6- (4-fluorophenylthio) benzo [c] [1,2] oxaborol-1 (3H) -ol (C44) P.f. 135-138 ° C. Starting material example: (2-bromo-4- (4-fluorophenylthio) methanol) 14e 1- (3- ((1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-5-yloxy ) methyl) phenyl) pentan-l-one (C45) P.f. 96-98 ° C. Starting material example: l- (3- ((4-brorao-3- (hydroxymethyl) phenoxy) methyl) phenyl) pentan-l-one. 14 f 2- (1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-5-yloxy) -1- (piperidin-1-yl) ethanone (C46) P.f. 158-163 ° C. Starting material example: 2- (4-bromo-3- (hydroxymethyl) phenoxy) -1- (piperidin-1-yl) ethanone. 14g 2- (1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-5-yloxy) -1- (4- (pyrimidin-2-yl) piperazin-1-yl) ethanone (C47) P.f. 190-195 ° C. Starting material example: 2- (4-bromo-3- (hydroxymethyl) phenoxy) -1- (4-pyrimidin-2-yl) piperazin-1-yl) ethanone. 1 h 6- (4- (pyridin-2-yl) piperazin-1-yl) benzo [c] [1,2] oxaborolyl (3H) -ol (C48) P.f. 135-138 ° C. Example start material: (2- bromo-4- (4-pyridin-2-yl) piperazin-1-yl) phenyl)) methanol, 14i 6-nitrobenzo [c] [1, 2] oxaborol-1 (3H) -ol (C49) P.f. 163-171 ° C. Starting material example: benzo [c] [1, 2] oxaborol-1 (3H) -ol. See JACS 82, 2172, 1960 for preparation. 14 j 6-aminobenzo [c] [1, 2] oxaborol-1 (3H) -ol (C50) P.f. 145-148 ° C. Starting material of exemplified nitrobenzo [c] [1,2] oxaborol-1 (3H) -ol. 14k 6- (dimethylamino) benzo [c] [1,2] oxaborol-1 (3H) -ol (C51) P.f. 120-123 ° C. Starting material example: 6-aminobenzo [c] [1,2] oxaborol-1 (3H) -ol. 1 1 N- (1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-6-yl) benzamide (C52) P.f. 186-193 ° C. Starting material example: 6-aminobenzo [c] [1,2] oxaborol-1 (3H) -ol. 14m 6- (4-phenylpiperazin-1-yl) benzo [c] [1,2] oxaborol-1 (3H) -ol (C53) P.f. 159-161 ° C. Starting material example: (2-bromo-4- (4-phenylpiperazin-1-yl) phenyl) methanol. 14th 6- (lH-indol-l-yl) benzo [c] [1, 2] oxaborol-1 (3H) -ol (C55) P.f. 135-140 ° C. Starting material example: (2-bromo-4- (lH-indol-l-yl) phenyl) methanol. 14p 6-morpholinobenzo [c] [1, 2] oxaborol-1 (3H) -ol (C56) P.f. 128-132 ° C. Starting material example: (2-bromo-4-morpholinophenyl) methanol. 14q 6- (1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-5-yloxy) nicotinonitrile (C57) P.f. 193-198 ° C. Starting material example: 6- (4-bromo-3- (hydroxymethyl) phenoxy) nicotinonitrile. 14 r 5- (fluoro-6-nitrobenzo [c] [1, 2] oxaborol-1 (3H) -ol (C58) ? F. 162-167 ° C. Starting material example: 5-fluorobenzo [c] [1,2] oxaborol-1 (3H) -ol. 14 s 5-bromo-6- (hydroxymethyl) benzo [c] [1,2] oxaborol-1 (3H) -ol (C59) P.f. > 257 ° C. Starting material example: (2,5-dibromo-4- (methoxymethyl) phenyl) methanol. 14t 3, 7-dihydro-l, 5-dihydroxy-lH, 3H-Benzo [1, 2-c: 4, 5-c '] bis [1, 2] oxaborol (C60) P.f. > 250 ° C. Starting material example: (2,5-dibromo-1, 4-phenylene) dimethanol. 14u 1- (1-hydroxy-l, 3-dihydroben2Q [c] [1,2] oxaborol-6-i1) -3-phenylurea (C61) H H OH CrYtX > P.f. 213-215 ° C. Starting material example: 6-aminobenzo [c] [1,2] oxaborol-1 (3H) -ol. 14v N- (1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-6-i1) benzenesulfonamide (C62) P.f. 175-184 ° C. Starting material example: 6-aminobenzo [c] [1,2] oxaborol-1 (3H) -ol. 14w N- (1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-6-yl) acetamide (C63) P.f. 176-185 ° C. Starting material example: 6-aminobenzo [c] [1,2] oxaborol-1 (3H) -ol. 14x 7- (hydroxymethyl) benzo [c] [1,2] oxaborol-1 (3H) -ol (C64) P.f. 241-250 ° C. Starting material example: (2-bromo-1,3-phenylene) dimethanol. 14 and 7-methylbenzo [c] [1, 2] oxaborol-1 (3H) -ol (C65) P.f. 107-111 ° C. Starting material example: (2-bromo-3-methylphenyl) methanol. 14z 6- (3- (phenylthio) -lH-indol-l-yl) benzo [c] [1, 2] oxaborol-1 (3H) -ol (C66) P.f. 159-163 ° C. Starting material example: (2-bromo-4- (3- (phenylthio) -lH-indol-1-yl) phenyl) methanol. 1 aa 3- (1- (1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-6-yl) -lH-indol-3-ylthio) propanenitrile (C67) P.f. 135-141 ° C. Starting material example: 3- (1- (3-bromo-4- (hydroxymethyl) phenyl) -lH-indole-3- iltio) propanonitrile. 14bb 6- (5-methoxy-lH-indol-l-yl) benzo [c] [1, 2] oxaborol-1 (3H) -ol (C68) P.f. 120-124 ° C. Starting material example: (2-bromo-4- (5-raetoxi-lH-indol-l-yl) phenyl) methanol. 14cc 5,6-methylenedioxybenzo [c] [1,2] oxaborol-1 (3H) -ol (C69) P.f. 185-189 ° C. Starting material example: (6-bromobenzo [d] [1,3] dioxol-5-yl) methanol. 14dd 6-amino-5-fluorobenzo [c] [1, 2] oxaborol-1 (3H) -ol (C70) P.f. 142-145 ° C. Starting material example: 6-nitro-5-fluorobenzo [c] [1,2] oxaborol-1 (3H) -ol. 14ee 6- (benzylamino) -5-fluorobenzo [c] [1,2] oxaborol-1 (3H) -ol (C71) P.f. 159-164 ° C. Starting material example: 6-amino-5-fluorobenzo [c] [1,2] oxaborol-1 (3H) -ol. 14 ff 6- (5-methoxy-3- (phenylthio) -lH-indol-1-yl) benzo [c] [1,2] oxaborol-1 (3H) -ol (C72) P.f. 135-141 ° C. Starting material example: (2-bromo-4- (5-methoxy-3- (phenylthio) -lH-indol-1-yl) phenyl) methanol. 14gg 3- (1- (1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-6-i1) -5-methoxy-lH-indol-3-ylthio) propanenitrile (C73) P.f. 149-154 ° C. Starting material example: 3- (1- (3-bromo-4- (hydroxymethyl) phenyl) -5-methoxy-lH-indol-3-ylthio) propanenitrile. 14hh 4- (1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-7-yloxy) benzonitrile (C74) P.f. 148-153 ° C. Starting material example: 4- (2-bromo-3- (hydroxymethyl) phenoxy) benzonitrile. 14ii 6- (5-chloro-lH-indol-l-yl) benzo [c] [1, 2] oxaborol-1 (3H) -ol (C75) P.f. 149-154 ° C. Starting material example: (2-bromo-4- (5-chloro-lH-indol-l-yl) phenyl) methanol. 1 j j 3- (5-chloro-1- (1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-6-yl) -lH-indol-3-ylthio) propanenitrile (C76) P.f. > 225 ° C. Starting material example: (3-bromo-4- (hydroxymethyl) phenyl) -5-chloro-lH-indol-3-ylthio) propanenitrile. 14 kk 6- (benzylamino) benzo [c] [1,2] oxaborol-1 (3H) -ol (C77) P.f. 126-133 ° C. Starting material example: 6-aminobenzo [c] [1,2] oxaborol-1 (3H) -ol. 1411 6- (dibenzylamino) benzo [c] [1, 2] oxaborol-1 (3H) -ol (C78) P.f. 115-123 ° C. Starting material example: 6-aminobenzo [c] [1,2] oxaborol-1 (3H) -ol. 14mm 7- (4- (lH-tetrazol-5-yl) phenoxy) benzo [c] [1,2] oxaborol-l (3H) -ol (C79) P.f. Decomposition at 215 ° C. Starting material example: 4- (1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-7-yl) benzonitrile. 14nn 6- (5-chloro-3- (phenylthio) -lH-indol-1-yl) benzo [c] [1,2] oxaborol-1 (3H) -ol (C80) P.f. 145-151 ° C. Example start material: (2- bromo-4- (5-chloro-3- (phenylthio) -lH-indol-1-yl) phenyl) methanol. 14pp 6- (4 - (pyrimidin-2-yl) piperazin-1-y1) benzo [c] [1,2] oxaborol-1 (3H) -ol (C82) P.f. NA ° C. Starting material example bromo-4- (4- (pyrimidin-2-yl) piperazin-1-y1) phenyl) methanol. 14qq 7- (benzyloxy) benzo [c] [1,2] oxaborol-1 (3H) -ol (C83) P.f. NA ° C. Starting material example: (3- (benzyloxy) -2-bromophenyl) methanol. 14rr 4- (1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-6-ylthio) pyridinium chloride (C84) P.f. NA ° C. Example start material: (2- Bromo-4- (pyridin-4-ylthio) phenyl) methanol. 14ss 6- (pyridin-2-ylthio) benzo [c] [1, 2] oxaborol-1 (3H) -ol (C85) P.f. NA ° C. Starting material example: (2-bromo- - (pyridin-2-ylthio) phenyl) methanol. 1 tt 7-fluorobenzo [c] [1, 2] oxaborol-1 (3H) -ol (C86) P.f. 120-124 ° C. Starting material example: (2-bromo-3-fluorophenyl) methanol. 14uu 6- (4- (trifluoromethyl) phenoxy) benzo [c] [1,2] oxaborol-1 (3H) | ol (C87) P.f. 98-105 ° C. Starting material example: (2-bromo-4- (4- (trifluoromethyl) phenoxy) phenyl) methanol. 14vv 6- (4-chlorophenylthio) benzo [c] [1,2] oxaborol-1 (3H) -ol (C88) P.f. 157-161 ° C. Starting material example: (2-bromo-4- (4-chlorophenylthio) phenyl) methanol. 14ww 6- (4-chlorophenylsulfinyl) benzo [c] [1,2] oxaborol-1 (3H) -ol (C89) P.f. 154-161 ° C. Starting material example: 6- (4-chlorophenylthio) benzo [c] [1,2] oxaborol-1 (3H) -ol. 14xx 6- (4-chlorophenylsulfonyl) benzo [c] [1,2] oxaborol-1 (3H) -ol (C9Q) P.f. 157-163 ° C. Starting material example: 6- (4-chlorophenylthio) benzo [c] [1,2] oxaborol-1 (3H) -ol. 14yy N- (1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-5-yl) -N- (phenylsulfonyl) benzenesulfonamide (C91) P.f. 142-152 ° C. Starting material example: N- (4-bromo-3- (hydroxymethyl) phenyl) -N- (phenylsulfonyl) benzenesulfonamide. 14 zz 6- (4- (trifluoromethyl) phenylthio) benzo [c] [1,2] oxaborol-l (3H) -ol (C92) P.f. 111-113 ° C. Starting material example: (2-bromo-4- (4- (trifluoromethyl) phenylthio) phenyl) methanol. 14aaa 6- (4- (trifluoromethyl) phenylsulfinyl) benzo [c] [1,2] oxaborol-1 (3H) -ol (C93) P.f. 79-88 ° C. Starting material example: 6- (4- (trifluoromethyl) phenylthio) benzo [c] [1,2] oxaborol-1 (3H) -ol. 14bbb 6- (4- (methylthio) phenylthio) enzo [c] [1,2] oxaborol-1 (3H) -ol (C94) P.f. 117-120 ° C. Starting material example: (2-bromo-4- (4- (methylthio) phenylthio) phenyl) methanol. 14ccc 6- (p-tolylthio) benzo [c] [1,2] oxaborol-1 (3H) -ol (C95) P.f. 139-144 ° C. Starting material example: (2-bromo-4- (p-tolylthio) phenyl) methanol. 14ddd 3- ((1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-5-yloxy) methyl) benzonitrile (C96) P.f. 147-150 ° C. Starting material example: 3- ((4-bromo-3- (hydroxymethyl) phenoxy) methyl) benzonitrile. Example 15 Precursors to CBO and CBE 15.1 2-bromo-5-fluoro- [1- (methoxymethoxy *) methyl] benzene (5b) To a solution of 3 (62.0 g, 293 mmol) in MeOH (400 mL) was added NaBH4 (5.57 g, 147 mmol) in portions at 0 ° C, and the mixture was stirred at room temperature for 1 hour. Water was added, and the solvent was removed under reduced pressure by half the volume. The mixture was poured into EtOAc and water. The organic layer was washed with brine and dried over anhydrous Na 2 SO 4. The solvent was removed under reduced pressure to give 4b, which was used for the next step without purification. TO a solution of 4b (60.8 g, 293 mmol) and i-Pr2NEt (61 mL, 0.35 mol) in CH2Cl2 was added chloromethyl methyl ether (27 mL, 0.35 mmol) at 0 ° C, and the mixture was stirred at room temperature overnight. Water was added, and the mixture was extracted with CHCl3. The organic layer was washed with brine and dried over Na2SC > 4 anhydrous. The solvent was removed under reduced pressure to give 5b (73.2 g, quadrant). 1 H NMR (300 MHz, CDCI3) d (ppm) 3.43 (s, 3H), 4.62 (s, 2H), 4.78 (s, 2H), 6.88 (td, J = 8.5, 3.2 Hz, 1H), 7.25 (dd, J = 9.6, 3.1 Hz, 1H), 7.48 (dd, J = 8.8, 5.3 Hz, 1H). 15.2 2-Bromo- [1- (methoxymethoxy) methyl] benzene (5a) This compound was made from 2-bromobenzyl alcohol in the same manner as compound 5b and used for the next step without purification. 15.3 2- [4-Fluoro-2- [(methoxymethoxy) methyl] phenyl] - [1,3,2] dioxaborlane (6) To a solution of 5b (16.2 g, 65.1 mmol) in THF (130 mL) were added sec-BuLi (1.4 M, 56 mL) and (MeO) 3B (14.5 mL, 130 mmol) at -78 ° C under nitrogen atmosphere, and the mixture was allowed to warm to room temperature and stirred for 2 hours. Water and 1N NaOH were added to the mixture, which was washed with Et20. The pH was then adjusted to 4 with HC1 1 N, and the mixture was extracted with EtOAc. The organic layer was washed with brine and dried over Na2SC >; 4 anhydrous. Then, the solvent was removed under reduced pressure to give acid boronic, which was used for the next step without purification. To a solution of the boronic acid in toluene (300 mL) was added ethylene glycol (3.29 g, 53 mmol), and the mixture was refluxed for 3 hours with a Dean-Stark trap. The solvent was removed under reduced pressure to give 6 (12.1 g, 77%). 1N-NMR (300 MHz, CDC13) d (ppm) 3.42 (s, 3H), 4.36 (s, 4H), 4.76 (s, 2H), 4.87 (s, 2H), 6.96 (td, J = 8.2, 2.6 Hz) , 1H), 7.26 (dd, J = 10.6, 2.6 Hz, 1H), 7.83 (dd, J = 8.2, 6.4 Hz, 1H). 15.4 2- (3-Chlorophenyl) [1, 3, 2] dioxaborolane (7b; R111 = 3-Cl-Ph) 3-Chlorophenylboronic acid (3.041 g, 19. 4 mmol) in 75 mL of dry THF under nitrogen atmosphere. Ethylene glycol (1.32 g, 21.3 mmol) was added and the solution was refluxed for 18 hours. The solution was allowed to cool and the THF was removed under reduced pressure to give 7b (3.55 g, 100%) as a brown oil which solidified on cooling in the freezer. NMR XH (300 MHz, CDC13) d (ppm) 4.39 (s, 4H), 7.32 (t, J = 7.9 Hz, 1H), 7.45 (dd, J = 8.2, 1.2 Hz, 1H), 7.67 (d, J) = 7.0 Hz, 1H), 7.78 (br s, 1H). Compounds 7a and 7c-k were synthesized in a manner similar to 7b. 15.5 2-Phenyl [1, 3, 2] dioxaborolane (7a; R111 = Ph) XH NMR (300 MHz, DMSO-d6) d (ppm) 4.30 (s, 4H), 7.35-7.41 (t, J = 8.2 Hz , 2H), 7.46-7.52 (m, 1H), 7.68-7.72 (dd, J = 6.2, 2.6 Hz, 2H). 15.6 2- (4-Chlorophenyl) [1, 3, 2] dioxaborolane (7c; R111 = 4-Cl-Ph) 1N-NMR (300 MHz, CDC13) d (ppm) 4.38 (s, 4H), 7.36 (d, J = 6.7 Hz, 2H), 7.74 (d, J = 7.0 Hz, 2H). | 15.7 2- (3-Fluorophenyl) [1, 3, 2] dioxaborolane (7d; Rii: L = 3-F-Ph) NMR XH (300 Hz, CDC13) d (ppm) 4.39 (s, 4H), 7.1-7.2 (m, 1H), 7.36 (td, J = 8.2, 5.6 Hz, 1H), 7.48 (dd, J = 9.1, 2. 6 Hz, 1H), 7.58 (d, J = 7.0 Hz, 1H). 15.8 2- (4-Fluorophenyl) [1, 3, 2] dioxaborolane. { you; RiLi = 4-F-Ph) t NMR XH (300 MHz, DMSO-d6) d (ppm) 4.29 (s, 4H), 7.17- 7.23 (t, J = 8.5 Hz, 2H), 7.71-7.76 (dd, J = 8.5, 6.1 Hz, 2H). . 9 2- (3-Methylphenyl) [1, 3, 2] dioxaborlane (7f; R111 = 3-Me-Ph) X H NMR (300 MHz, DMSO-d 6) d (ppm) 2.31 (s, 3 H), 4.31 (s, 4 H), 7.29-7.32 (m, 2 H), 7.50-7.53 (m, 2 H). 15.10 2-styryl [1, 3, 2] dioxaborlane (7h; Ri i = styryl) NMR XH (300 MHz, DMSO-d6) d (ppm) 4.20 (s, 4H), 6.15 (d, J = 18.5 Hz, 1H), 7.31-7.39 (m, 4H), 7.56 (dd, J = 1.5, 7.6 Hz, 2H). 15.11 2- (Tiofen-3-yl) [1, 3, 2] dioxaborlane (7j; R111 = thiophen-3-yl) 1 H-NMR (300 MHz, DMSO-d6) d (ppm) 4.27 (s, 4H), 7.30 (dd, J = 4.8, 0.9 Hz, 1H), 7.58 (dd, J = 4.5, 2.4 Hz, 1H), 8.03 (dd, J = 2.7, 1.2 Hz, 1H). 15.12 2- (4-Methylthiophen-3-yl) [1, 3, 2] dioxaborolane (7k; R111 = 4- methylthiophen-3-yl) NMR XH (300 MHz, DMSO-d6) d (ppm) 2.31 (s, 3H), 4.25 (s, 4H), 7.13-7.14 (m, 1H), 7.93 (d, J = 3.0 Hz, 1H). Example 16 CBE 16.1 1- (3-Chlorophenyl) -1,3-dihydro-5-fluoro-2, 1-benzoxazole (9f) Compound 5b (1.06 g, 4.20 mmol) was dissolved in 50 mL of dry THF under an atmosphere of nitrogen and cooled to -78 ° C. It was slowly added to the solution ter-BuLi (1.7 M in pentane, 5.3 mL). After stirring for 10 minutes at -78 ° C, compound 7b (764 mg, 4.20 mmol) in 10 mL of dry THF was added and the solution was stirred for 0.5 additional hours. The solution was then allowed to warm to room temperature and stirred for 18 hours. The solvent was removed under reduced pressure, and the residue was partitioned between 40 mL of H20 and 80 mL of diethyl ether. The solution was vigorously stirred for several minutes, then neutralized (pH 7) with 6N HC1. The organic layer was separated and the aqueous solution was extracted again with ether (2 x 80 mL). The ether extractors were combined, dried over MgSO4, filtered and evaporated to give crude 8f (1.22 g) as a yellow oil, which was used for the next step without purification. Compound 8f (700 mg, 2.30 mmol) was dissolved in 46 mL of THF and 4 mL of concentrated HC1. The solution is stirred at room temperature for 12 hours. Then water (10 mL) was added and the THF was removed under reduced pressure. This gave a suspension. The precipitates were filtered under vacuum and washed with water (10 mL) then with hexanes (5 mL) and dried to give compound 9f (334. mg, 59%) as a white solid: m.p. 112-114 ° C. NMR XH (300 MHz, DMSO-d6) d (ppm) 5.15 (s, 2H), 7.02-7.08 (t, J = 8.8 Hz, 1H), 7.14-7.17 (d, J = 8.8 Hz, 1H), 7.23 -7.33 (m, 2H), 7.65-7.72 (m, 3H); ESI-MS m / z 247.08, 249.03 (M-H) ~; HPLC purity: 97.1%; Analyzed (Ci3H9BClFO) C, H. Compounds 9a-e, 9g-j, 10a, b and 12-15 were synthesized in a manner similar to 9f. 16.1 1, 3-Dihydro-l-phenyl-2, 1-benzoxazole (9a) Colorless oil; NMR XH (300 MHz, DMS0-d6) d (ppm) 5.41 (s, 2H), 7.43-7.61 (m, 6H), 8.11 (d, J = 9.4 Hz, 2H), 8.18 (d, J = 8.2 Hz , 1 HOUR); ESI-MS m / z not observed; HPLC purity: 95.5%. 16.2 1, 3-Dihydro-5-fluoro-l-phenyl-2, 1-benzoxazole (9b) P.f. 90-99 ° C; 1N-NMR (300 MHz, DMSO-d6) d (ppm) 5.37 (s, 2H), 7.22 (dt, · J = 2.3, 8.9 Hz, 1H), 7.38 (dd, J = 2.1, 9.4 Hz, 1H), 7.45-7.57 (m, 3H), 8.06 (dd, J = 1.8, 7.9 Hz, 2H), 8.16 (dd, J = 5.9, 8.2 Hz, 1H); ESI-MS m / z 213 (M + H) +; HPLC purity: 95.1%. 16. 3- 1- (3-Chlorophenyl) -1,3-dihydro-2, 1-benzoxazole (9c) Colorless oil; 1 H NMR (300 Hz, DMSO-d 6) d (ppm) 5.26 (s, 2 H), 7.29-7.45 (m, 5 H), 7.77-7.86 (m, 3 H); ESI-MS m / z not observed; HPLC purity: 96.0%; Analyzed (Ci3Hi0BClO) C, H. 16.4 1, 3-Dihydro-1- (3-fluorophenyl) -2, 1-benzoxazole (9d) Colorless oil; 1 H NMR (300 MHz, DMSO-d 6) d (ppm) 5.28 (s, 2 H), 7.23 (m, 1 H), 7.34 (m, 1 H), 7.41-7.48 (m, 3 H), 7.57-7.61 (dd, J = 9.6, 2.6 Hz, 1H), 7.74-7.77 (d, J = 7.3 Hz, 1H), 7.93-7.95 (d, J = 7.3 Hz, 1H); ESI-MS m / z not observed; HPLC purity: 98.3%; Analyzed (Ci3Hi0BFO) C, H. 16.5 1, 3-Dihydro-1- (4-fluorophenyl) -2, 1-benzoxazole (9e) P.f. 53-55 ° C; NMR 1 (300 MHz, DMSO-d6) d (ppm) 5.37 (s, 2H), 7.26-7.32 (m, 2H), 7.42 (m, 1H), 7.53-7.55 (m, 2H), 8.11-8.16 ( m, 3H); ESI-MS m / z not observed; HPLC purity: 99.3%; Analyzed (Ci3H10BFO) C, H. 16.6 1, 3-Dihydro-5-fluoro-1- (3-fluorophenyl) -2, 1-benzoxazole (9g) P.f. 80-82 ° C; RMN ?? (300 MHz, DMSO-d6) d (ppm) 5.20 (s, 2H), 7.06-7.18 (m, 2H), 7.22 (dd, J = 9.6, 1.8 Hz, 1H), 7.39 (td, J = 7.8, 5.4 Hz, 1H), 7.49 (dd, J = 9.9, 2.7 Hz, 1H), 7.63 (dd, J = 6.9, 0.9 Hz, 1H), 7.83 (dd, J = 8.1, 5.7 Hz, 1H); ESI-MS m / z not observed; HPLC purity: 98.5%; Analyzed (Ci3H9BF20) C, H. 16. 7 1, 3-Dihydro-5-fluoro-1- (4-fluorophenyl) -2, 1-benzoxazole (9h) P.f. 75-77 ° C; RN XH (300 MHz, DMSO-d6) d (ppm) 5.33 (s, 2H), 7.19-7.30 (m, 3H), 7.36 (dd, J = 9.9, 2.1 Hz, 1H), 8.05-8.14 (m, 3H); ESI-MS m / z not observed; HPLC purity: 99.0%; Analyzed (Ci3H9BF20) C, H. 16.8 1, 3-Dihydro-5-fluoro-1- (3-methylphenyl) -2, 1-benzoxazole (9i) P.f. 48-49 ° C; NMR XH (300 MHz, DMSO-d6) d (ppm) 2.37 (s, 3H), 5.36 (s, 2H), 7.25 (m, 1H), 7.3-7.5 (m, 3H), 7.8-7.9 (m, 2H), 8.20 (dd, J = 7.9, 5.9 Hz, 1H); ESI-MS m / z 227 (M + H) +; HPLC purity: 99.8%; Analyzed (Ci 4 H 12 BFO) C, H. 16.9 1, 3-Dihydro-5-fluoro-1- (4-methylphenyl) -2, 1-benzoxazole 19β P.f. 48-49 ° C; NMR 1 (300 MHz, DMSO-d6) d (ppm) 2.36 (s, 3H), 5.35 (s, 2H), 7.25 (m, 1H), 7.29 (d, J = 7.6 Hz, 2H), 7. 40 (dd, J = 9.4, 1.5 Hz, 1H), 7.99 (d, J = 7.6 Hz, 2H), 8.20 (dd, J = 7.9, 5.6 Hz, 1H); ESI-MS m / z 227 (M + H) +; HPLC purity: 98.9%; Analyzed (Ci4Hi2BFO) C, H. 16.10 1, 3-Dihydro-1-styryl-2, 1-benzoxazole (10a) P.f. 57-59 ° C; NMR XH (300 MHz, DMSO-d6) d (ppm) 5.33 (s, 2H), 6.85 (d, J = 18.8 Hz, 1H), 7.38-7.46 (m, 4H), 7.56 (d, J = 4.7 Hz , 2H), 7.64 (d, J = 7.9 Hz, 2H), 7.83 (d, J = 18.8 Hz, 1H), 8.14 (d, J = 7.3 Hz, 1H); ESI-MS m / z 221 (M + H) +; HPLC purity: 98.5%; Analyzed (Ci3Hi0BFO - 0.1H20) C, H. 16.11 1, 3-Dihydro-5-fluoro-l-styryl-2, 1-benzoxazole (10b) P.f. 84-86 ° C; 1N-NMR (300 MHz, DMSO-d6) d (ppm) 5.32 (s, 2H), 6.86 (d, J = 18.8 Hz, 1H), 7.24 (td, J = 2.3, 10.6 Hz, 1H), 7.38-7.47 (m, 4H), 7.74 (d, J = 7.0 Hz, 2H), 7.83 (d, J = 18.8 Hz, 1H), 8.19 (dd, J = 5.9, 8.2, 1H); ESI-MS m / z 239 (M + H) +; HPLC purity: 99.1%; Analyzed (C13H10BFO) C, H. 16. 12 1, 3-Dihydro-5-fluoro-1- (furan-3-yl) -2, 1-benzoxazole (12) Colorless oil; 1N-NMR (300 MHz, DMSO-d6) d (ppm) 5.34 (s, 2H), 6.84 (m, 1H), 7.24 (m, 1H), 7.37-7.40 (d, J = 9.4 Hz, 1H), 7.83 (m, 1H), 8.14-8.18 (dd, J = 8.2, 5.9 Hz, 1H), 8.49 (m, 1H); ESI-MS m / z 203 (M + H) +; HPLC purity: 96.9%; Analyzed (CnH8BF02) C, H. 16.13 1, 3-Dihydro-5-fluoro-1- (thiophen-3-yl) -2, 1-benzoxazole (13) P.f. 33-35 ° C; 1 H NMR (300 MHz, DMSO-d 6) d (ppm) 5.33 (s, 2 H), 7.24 (m, 1 H), 7.35-7.38 (d, J = 9.3 Hz, 1 H), 7.65 (m, 2 H), 8.17 -8.22 (dd, J = 8.4, 6.3 Hz, 1H), 8.48 (m, 1H); ESI-MS m / z 219 (M + H) +; HPLC purity: 97.8%; Analyzed (CiiH8BFOS) C, H. 16. 14 1, 3-Dihydro-5-fluoro-1- (4-methylthiophen-3-yl) -2, 1-benzoxazole (14) P.f. 51-53 ° C; XH NMR (300 MHz, DMSO-d6) d (ppm) 2.46 (s, 3H), 5.36 (s, 2H), 7.20-7.27 (m, 2H), 7.37-7.40 (dd, J = 9.4, 2.1 Hz, 1H), 8.14-8.19 (dd, J = 8.2, 5.9 Hz , 1H), 8.48-8.49 (d, J = 2.6 Hz, 1H)); ESI-MS m / z 233 (M + H) +; HPLC purity: 100%; Analyzed (Ci2Hi0BFOS) C, H. 16.15 1, 3-Dihydro-5-fluoro-l-vinyl-2, 1-benzoxazole (11) Compound 5b (2.0 g, 8.0 mmol) in THF was cooled (30 mL) at -78 ° C and tert-butyllithium (9.9 mL, 16.8 mmol) was slowly added as a 1.7 M solution in pentane. After stirring at -78 ° C for 30 minutes, dibutyl ester of vinyl boronic acid was added dropwise. The mixture was stirred at -78 ° C for 1 hour, then warmed to room temperature and stirred overnight. Concentrated HC1 (4 mL) was added and stirred at room temperature for 4 hours. Water (10 mL) was added and the THF was removed under reduced pressure. The residue was extracted with ethyl ether, washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (hexane / ethyl acetate 9: 1) to give 11 (383 mg, 30%) as a yellowish oil; H NMR (300 MHz, DMSO-d6) d (ppm) 5.27 (s, 2H), 6.25 (t, J = 8.5 Hz, 1H), 6.50 (d, J = 9.4 Hz, 2H), 7. 06-7.15 (m, 2H), 7.89 (dd, J = 5.6, 7.9 Hz, 1H); ESI-MS m / z (M + H) +; HPLC purity: 98.7%; Analyzed (C9H8BFO) · 0.1H20) C, H. 16.16 3- (1, 3-Dihydro-5-fluoro-2, 1-benzoxaborol-1-yl) pyridine (15) To a solution of 3-bromopyridine (731 mg , 4.63 mmol) in THF (5 mL) was added isopropylmagnesium chloride (1M in THF, 2.3 mL) at room temperature under nitrogen atmosphere, and the mixture was stirred for 1 hour. To the mixture was added compound 6 (1.11 g, 4.63 mmol) in THF (4 mL), and the mixture was stirred at room temperature overnight. Water was added and the pH was adjusted to 7 with 1N HC1. The mixture was then extracted with ethyl acetate. The solvent was removed under reduced pressure, and the residue was dissolved in THF (30 mL). To the mixture was added 1N HC1 (10 mL), and the mixture was refluxed overnight. The pH was adjusted to 7 with aqueous NaHCO 3 and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous Na 2 SO 4. The solvent was removed under reduced pressure and the residue was recrystallized from i-Pr20 to give compound 15 (76 mg, 7.7%): m.p. 210-212 ° C; RN XH (300 MHz, DMSO-de) d 4.94 (s, 2H), 6.9-7.1 (m, 2H), 7.36 (br s, 1H), 7.66 (dd, J = 6.7, 5.3 Hz, 1H), 8.19 (d, J = 6.7 Hz, 1H), 8.24 (br s, 1H), 8.64 (d, J = 5.3 Hz, 1H): ESI-MS m / z 214 (M + H) +; Analyzed (d2H9BFNO) · 0.6 H20) C, H, N.

Example 17 Precursors of CBO 17.1 2-Bromo-5-fluoro- [1- (methoxymethoxy) ethyl] benzene (18c) To a solution of compound 3 (4.23 g, 20.0 mmol) in THF (30 mL) was added MeMgBr (1.4 mol / L in THF; 18 mL) at -78 ° C under nitrogen atmosphere, and the mixture was stirred for 2 hours while avoiding warming to room temperature. The reaction was quenched with HC1 2 N, and the mixture was extracted with EtOAc. The organic layer was washed with brine and dried over anhydrous Na 2 SO 4. The solvent was removed under reduced pressure. To a solution of the residue (4.62 g) in CH2C12 (100 mL) was added i-Pr2NEt (5.2 mL, 30 mmol) and methyl chloromethyl ether (2.0 mL, 26 mmol) at 0 ° C, and the reaction mixture was added. stirred at room temperature overnight. Water was added, and the mixture was extracted with CHC13. The organic layer was washed with brine and dried over anhydrous Na 2 SO 4. The solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate 15: 1) to give 18c (4.97 g, 2 steps 94%); RN 1ti (300 MHz, CDC13) d (ppm) 1.43 (d, J = 6.5 Hz, 3H), 3.38 (s, 3H), 4.55 (d, J = 6.5 Hz, 1H), 4.63 (d, J = 6.5 Hz, 1H), 5.07 (q, J = 6.5 Hz, 1H), 6.85 (m, 1H), 7.25 (dd, J = 9.7, 2.6 Hz, 1H), 7.46 (dd, J = 8.8, 5.3 Hz, 1H ). 17.2 2-Bromo-5-chloro-l- (methoxymethoxymethyl) benzene (18d) To a solution of 2-bromo-5-chlorobenzoic acid (5.49 g, 23.3 mmol) in anhydrous THF (70 mL) under nitrogen was added dropwise a solution of BH3-THF (1.0 M, 55 mL) at 0 ° C and the reaction mixture was stirred overnight at room temperature. ambient. Then, the mixture was cooled in an ice bath and MeOH (20 mL) was added dropwise to decompose excess BH3. The resulting mixture was stirred until no bubbles were released and then 10% NaOH (10 mL) was added. The mixture was concentrated and the residue was mixed with water (200 mL) and extracted with EtOAc. The residue from the rotary evaporation was purified by silica gel column chromatography (hexane / EtOAc 5: 1) to give 2-bromo-5-chlorobenzyl alcohol as a white solid (4.58 g., 88%): 1 H NMR (300 MHz, DMSO-d 6) d (ppm) 7.57 (d, J = 8.7 Hz, 1H), 7.50-7.49 (m, 1H), 7.28-7.24 (m, 1H), 5.59 (5, J = 6.0 Hz, 1H), 4.46 (d, J = 6.0 Hz, 2H). The 2-bromo-5-chlorobenzyl alcohol obtained above was dissolved in CH2C12 (150 mL) and cooled to 0 ° C in an ice bath. To this solution under nitrogen were added in sequence i-Pr2NEt (5.4 mL, 31 mmol) and methyl chloromethyl ether (2.0 mL, 26 mmol). The reaction mixture was stirred overnight at room temperature and washed with water saturated with NaHCO 3 and then brine. The residue after rotary evaporation was purified by silica gel column chromatography (hexane / EtOAc 5: 1) to give 18d (4.67 g, 85%) as a colorless oil: 1 H NMR (300 MHz, DMSO-d6) d (ppm) 3.30 (s, 3H), 4.53 (s, 2H), 4.71 (s, 2H), 7.32 (dd, J = 8.4, 2.4 Hz, 1H), 7.50 (dd) , J = 2.4, 0.6 Hz, 1H), 7.63 (d, J = 8.7 Hz, 1H). 17.3 4-Bromo-3- (methoxymethoxymethyl) toluene (18e) This compound was made from 2-bromo-5-methylbenzoic acid in the same manner as compound 18d: RN XH (300 MHz, DMSO-de) d ( ppm) 2.27 (s, 3H), 3.30 (s, 3H), 4.51 (s, 2H), 4.68 (s, 2H), 7.05 (dd, J = 7.9, 2.3 Hz, 1H), 7.30 (d, J = 1.5 Hz, 1H), 7.46 (d, J = 8.2 Hz, 1H). 17.4 2-Bromo-5-methoxy-1- (methoxymethoxymethyl) benzene (18g) This compound was made from 2-bromo-5-methoxybenzoic acid in the same manner as compound 18d: 1 H NMR (300 MHz, DMSO- de) d 3.30 (s, 1H), 3.74 (s, 3H), 4.50 (s, 2H), 4.69 (s, 2H), 6.83 (dd, J = 8.8, 2.9.Hz, 1H), 7.40 (d, J = 2.9 Hz, 1H), 7.48 (d, J = 8.8 Hz, 1H). 17.5 2-Bromo-l, 5-bis (methoxymethoxymethyl) benzene (18h) This compound was made from 4-bromo-1,3-phthalic acid in the same manner as compound 18d: 1 H NMR (300 MHz, CDC13 ) d (ppm) 3.28 (s, 3H), 3.30 (s, 3H), 4.50 (s, 2H), 4.54 (s, 2H), 4.64 (s, 2H), 4.69 (s, 2H), 7.20 (dd, J = 8.8, 2.5 Hz, 1H), 7.46 (d, J = 2.5 Hz, 1H), 7.58 (d, J = 8.8 Hz, 1H). 17.6 2-Bromo-4,5-difluoro-1- (methoxymethoxymethyl) benzene (18k) This compound was made from 2-bromo- -difluorobenzoic acid in the same manner as compound 18d: NMR XH (300 MHz, CDC13) d (ppm) 3.42 (s, 3H), 4.57 (d, J = 1.2 Hz, 2H), -4.76 (s, 2H) , 7.3-7.5 (m, 2H). 17.7 2-Bromo-6-fluoro-1- (methoxymethoxymethyl) benzene (181) This compound was made from 2-bromo-β-fluorobenzoic acid in the same manner as compound 18d: XH NMR (300 MHz, CDCl 3) d (ppm) 3.43 (s, 3H), 4.74 (s, 2H), 4.76 (d, J = 2.1 Hz, 2H), 7.05 (t, J = 9.1 Hz, 1H), 7.18 (td, J = 8.2, 5.9 Hz, 1H), 7.40 (d, J = 8.2 Hz, 1H). 17.8 2-Bromo-4-fluoro-1- (methoxymethoxymethyl) benzene (18m) This compound was made from 2-bromo-5-fluorobenzoic acid in the same manner as compound 18d and used for the next step without purification . 17.9 4-Bromo-3- (methoxymethoxymethyl) benzonitrile (18f) To a solution of 17 (10.0 g, 49.5 mmol) in carbon tetrachloride (200 mL) were added N-bromosuccinimide (8.81 g, 49.5 mmol) and 2.2 '-azobis (isobutyronitrile) (414 mg, 5% by mol), and the mixture was refluxed for 3 hours. Water was added, and the mixture was extracted with chloroform. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. To the residue were added dimethylformamide (150 mL) and sodium acetate (20.5 g, 250 mmol), and the mixture was stirred at 80 ° C overnight.

Water was added, and the mixture was extracted with ether. The organic layer was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. To the residue was added methanol (150 mL) and 1 mol / L sodium hydroxide (50 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated to approximately one third of the volume under reduced pressure. Water and hydrochloric acid were added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography (hexane / ethyl acetate 3: 1) followed by titration with dichloromethane to give 2-bromo-5-cyanobenzyl alcohol (4.63 g, together 44%): 1H NMR (300 Hz, DMSO-d6) d (ppm) 4.51 (d, J = 5.9 Hz, 2H), 5.67 (t, J = 5.6 Hz, 1H), 7.67 (dd, J = 8.2, 2.0 Hz, 1H), 7.80 (s, J = 8.2 Hz, 1H), 7.83 (d, J = 2.0 Hz, 1H). To a solution of 2-bromo-5-cyanobenzyl alcohol (4.59 g, 21.7 mmol) in dichloromethane (80 mL) were added diisopropylethylamine (5.6 mL, 32 mmol) and methyl chloromethyl ether (2.3 mL, 30 mmol) at 0 °. C, and the reaction mixture was stirred at room temperature overnight. Water was added, and the mixture was extracted with chloroform. The organic layer was washed with brine and dried over anhydrous sodium sulfate.

The solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (hexane ethyl acetate 6: 1) to give 18f (4.08 g, 71%): RN 1ti (300 Hz, CDC13) d (ppm) 3.43 (s, 3H) , 4.65 (s, 2H), 4.80 (s, 2H), 7.43 (dd, J = 8.2, 4.1 Hz, 1H), 7.66 (d, J = 8.2 Hz, 1H), 7.82 (d, J = 4.1 Hz, 1 HOUR) . 17.10 2-Bromo-5-trifluoromethyl-1- (methoxymethoxymethyl) benzene (18i) This compound was made from 2-bromo-5-trifluoromethylbenzaldehyde in the same manner as compound 5b and used for the next step without purification. 17. 11 l-Bromo-2- (methoxymethoxymethyl) naphthalene (18 j) This compound was made from 1-bromonaphtaldehyde in the same manner as compound 5b: 1 H NMR (300 MHz, CDCl 3) d (ppm) 3.42 (s, 3H), 4.75 (s, 2H), 4.81 (s, 2H), 7.5-7.7 (m, 3H), 7.99 (d, J = 7.7 Hz, 2H), 8.22 (d, J = 7.7 Hz, 1H). 17.12 1, 3-Dihydro-l-hydroxy-2, 1-benzoxazole (19a) This compound was purchased from Lancaster Synthesis. 17.13 1, 3-Dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole (19b) To a solution of 5b (73.2 g, 293 mmol) in dry THF (400 mL) was added n-butyllithium ( 1.6 M in hexanes 200 mL) for 45 minutes at -78 ° C under nitrogen atmosphere. He anion precipitated. After 5 minutes, (i-PrO) 3B (76.0 mL, 330 mmol) was added over 10 minutes, and the mixture was allowed to warm to room temperature for 1.5 hours. Water and 6N HCl were added (55 mL), and the solvent was removed under reduced pressure to approximately half volume. The mixture was poured into ethyl acetate and water. The organic layer was washed with brine and dried over anhydrous Na 2 SO 4. The solvent was removed under reduced pressure. To a solution of the residue in tetrahydrofuran (360 mL) was added 6N HCl (90 mL), and the mixture was stirred at 30 ° C overnight. The solvent was removed under reduced pressure to approximately half volume. The mixture was poured into ethyl acetate and water. The organic layer was washed with brine and dried over anhydrous Na 2 SO 4. The solvent was removed under reduced pressure, and the residue was treated with i-Pr20 / hexane to give 19b (26.9 g, 60%) as a white powder: m.p. 118-120 ° C; NMR? (300 MHz, DMSO-d6) d (ppm) 4.95 (s, 2H), 7.15 (m, 1H), 7.24 (dd, J = 9.7, 1.8 Hz, 1H), 7.74 (dd, J = 8.2, 6.2 Hz , 1H), 9.22 (s, 1H); ESI-MS m / z 151 (M-H) ~; HPLC purity: 97.8%; Analyzed (C7H6BF02) C, H. 17.14 1, 3-Dihydro-5-fluoro-l-hydroxy-3-methyl-2, 1-benzoxaborolane (19c) This compound was worked up from 18c in the same manner as the compound 19b: pf 72-76 ° C. 1 H NMR (300 MHz, DMSO-d6) d (ppm) 1.37 (d, J = 6.4 Hz, 3H), 5.17 (q, J = 6. 4 Hz, 1H), 7.14 (m, 1H), 7.25 (dd, J = 9.7, 2.3 Hz, 1H), 7.70 (dd, J = 8.2, 5.9 Hz, 1H), 9.14 (s, 1H). ESI-MS m / z 165 (M-H) ~; HPLC purity: 95.2%; Analyzed (C8H9B02) C, H. 17.15 5-Chloro-l, 3-dihydro-l-hydroxy-2, 1-benzoxazole (19d) This compound was worked up from 18d in the same manner as compound 19b: p.f. 142-144 ° C. 1 H NMR (300 MHz, DMSO-de) d (ppm) 4.96 (s, 2H), 7.38 (d, J = 7.8 Hz, 1H), 7.49 (s, 1H), 7.71 (d, J = 7.8 Hz, 1H ), 9.30 (s, 1H); ESI-MS m / z 167 (M-H) ~; HPLC purity: 99.0%; Analyzed (C7H6BC102 - 0.1 H20) C, H. 17.16 1, 3-Dihydro-l-hydroxy-5-methyl-2, 1-benzoxazole (19e) This compound was made from 18e in the same manner as compound 19b : pf 124-128 ° C. NMR XH (300 MHz, DMSO-d6) d (ppm) 2.33 (s, 3H), 4.91 (s, 2H), 7.13 (d, J = 7.2 Hz, 1H), 7.18 (s, 1H), 7.58 (d , J = 7.2 Hz, 1H), 9. 05 (s, 1H); ESI-MS m / z 147 (M-H) ~; HPLC purity: 99.0%; Analyzed (C8H9B02) C, H. 17.17 1, 3-Dihydro-l-hydroxy-5-methoxy-2, 1-benzoxazole (19g) This compound was made from 18g in the same manner as compound 19b: p.f. 102-104 ° C. 1 H NMR (300 MHz, DMSO-de) d (ppm) 3.77 (s, 3H), 4.91 (s, 2H), 6.88 (d, J = 8.1 Hz, 1H), 6.94 (s, 1H), 7.60 (d, J) = 8.1 Hz, 1H), 8.95 (s, 1H); ESI-MS m / z 163 (M-H) ~; HPLC purity: 100%; Analyzed (C8H9B03) C, H. 17.18 1, 3-Dihydro-l-hydroxy-5-hydroxymethyl-2, 1-benzoxazole (19h) This compound was worked up from 18h in the same manner as compound 19b: p.p. 124-128 ° C. 1 H NMR (300 MHz, DMSO-de) d (ppm) 4.53 (d, 2H), 4.94 (s, 2H), 5.24 (t, 1H), 7.26 (d, 1H), 7.33 (s, 1H), 7.64 (d, 1H), 9.08 (s, 1H); ESI-MS m / z 163 (MH) "; purity by HPLC: 100% 17.19 1,3-Dihydro-1-hydroxy-5-trifluoromethoxy-benzoxazole (19i) This compound was made from 18i in the same way as compound 19b: mp 113-118 ° C. 1 H NMR (300 MHz, DMSO-de) d (ppm) 5.05 (s, 2H), 7.65-7.68 (d, J = 7.5 Hz, 1H), 7.78 (s, 1H), 7.90-7.93 (d, J = 7.8 Hz , 1H), 9.47 (s, 1H); ESI-MS m / z 201 (MH) "; purity by HPLC: 100% 17.20 1, 3-Dihydro-l-hydroxy-2, 1-naphtho [2, 1-d] oxaborol (19j) This compound was made from 18 j in the same manner as compound 19b: mp 139-143 ° C. 1 H NMR (300 MHz, DMSO-d 6) d (ppm) 5.09 (s, 2 H), 7.59-7.47 (m, 3 H) , 7.95 (d, J = 7.5 Hz, 1H), 7.99 (d, J = 8.1 Hz, 1H), 8.28 (dd, J = 6.9, 0.6 Hz, 1H), 9.21 (s, 1H); ESI-MS m / z 185 (M + H) V Analyzed (C H9B02) C, H. 17.21 1, 3-Dihydro-4-fluoro-l-hydroxy-2, 1-benzoxazole (191) This compound was made up of from 18L in the same manner as compound 19b: 1 H NMR (300 MHz, DMSO-d6) d (ppm) 5.06 (s, 2H), 7.26 (ddd, J = 9.7, 7.9, 0.6 Hz, 1H), 7.40 (td, J = 8.2, 4.7 Hz, 1H), 7.55 (d, J = 7.0 Hz, 1H), 9.41 (s, 1H); ESI-MS m / z 151 (MH) "; purity by HPLC: 98.7%; Analyzed (C7H6BF02) C, H. 17.22 1, 3-Dihydro-6-fluoro-l-hydroxy-2, 1-benzoxazole (19m) This compound was made from 18m in the same manner as compound 19b: 1H NMR (300 MHz, DMSO-d6) d (ppm) 4.95 (s, 2H), 7.29 (td, J = 9.0, 2.7 Hz, 1H ), 7.41-7.46 (m, 2H), 9.29 (s, 1H), ESI-MS m / z 151 (MH) "; HPLC purity: 100%; Analyzed (C7H6BF02) C, H. 17.23 5,6-Difluoro-1,3-dihydro-l-hydroxy-2, 1-benzoxazole (19k) To a solution of 18k (2.97 g, 11.1 mmol) and (i-PrO 3B (2.8 mL, 12 mmol) in THF (30 mL) was added n-BuLi (1.6 mol / L in hexane, 7.5 mL) for 30 minutes at -78 ° C under nitrogen atmosphere, and the mixture was stirred for 2 hours while it is allowed to warm to room temperature. The The reaction was quenched with HC1 2 N, and the mixture was extracted with EtOAc. The organic layer was washed with brine and dried over anhydrous Na 2 SO 4. The solvent was removed under reduced pressure. To a solution of the residue in THF (25 mL) was added 6N HC1 (5 mL), and the mixture was stirred at room temperature overnight. Water was added and the mixture was extracted with EtOAc. The organic layer was washed with brine and dried over anhydrous Na 2 SO 4. The solvent was removed under reduced pressure. Recrystallization from EtOAc / i-Pr20 gave 19k (1.14 g, 60%) as a white powder: m.p. 134-140 ° C. NMR XH (300 MHz, DMSO-d6) d (ppm) 4.94 (s, 2H), 7.50 (dd, J = 10.7, 6.8 Hz, 1H), 7.62 (dd, J = 9.7, 8.2 Hz, 1H), 9.34 (s, 1H). ESI-MS m / z 169 (M-H) ~; HPLC purity: 96.6%; Analyzed (C7H5BF202) C, H. 17.24 5-Cyano-l, 3-dihydro-l-hydroxy-2, 1-benzoxazole (19f) This compound was worked up from 18f in the same manner as compound 19k: p.f. 98-101 ° C. NMR XH (300 MHz, DMSO-d6) d (ppm) 5.03 (s, 2H), 7.76 (d, J = 8.2 Hz, 1H), 7.89 (d, J = 8.2 Hz, 1H), 7.90 (s, 1H) ), 9.53 (s, 1H); ESI-MS m / z 158 (MH) "; purity by HPLC: 97.7% 17.25 1, 3-Dihydro-7-fluoro-l-hydroxy-2, 1-benzoxazole (19n) To a solution of 20 (2.00 g , 15.9 mmol) and TMEDA (5.70 mL, 38.0 mmol) in THF (100 mL) was added sec-butyllithium (25 mL, 35.0 mmol) as a 1.4 M solution at -78 ° C.

The mixture was stirred at -78 ° C for 1 hour, before (i-PrO) 3B (8.10 mL, 35.0 mmol) was added. The reaction was warmed to room temperature very slowly, then stirred overnight. Water was added, and the pH was adjusted to 12, then washed with ethyl ether. The aqueous layer was acidified to pH 2 using 6N HC1, then extracted with ethyl ether, washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography (hexane / ethyl acetate 2: 1) to give 19n (270 mg) as a white solid: m.p. 120-124 ° C. NMR XH (300 MHz, DMSO-d6) d (ppm) 4.99 (s, 2H), 7.00 (t, J = 8.7 Hz, 1H), 7.21 (d, J = 7.8 Hz, 1H), 7.48 (td, J = 5.1, 7.8 Hz, 1H), 9.25 (s, 1H); ESI-MS m / z 151 (M-H) ~; HPLC purity: 97.4%; Analyzed (C8H6BN02) C, H. Example 18 Benzoxaborine 18.1 2-Bromo-5-fluorophenylacetaldehyde (21a) A mixture of compound 3 (4.23 g, 20.0 mmol), (methoxymethyl) triphenylphosphonium chloride (8.49 g, 24.0 mmol), and Potassium tert-butoxide (2.83 g, 24.0 mol) in N, N-dimethylformamide (50 mL) was stirred at room temperature overnight. The reaction was quenched with 6N hydrochloric acid, and the mixture was extracted with ethyl acetate. The organic layer was washed with water twice and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. To the residue were added tetrahydrofuran (60 mL) and 6 N hydrochloric acid, the mixture was heated to reflux for 8 hours. Water was added, and the mixture was extracted with ether. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give 21a (3.60 g, 83%): XH NMR (300 MHz, CDC13) d (ppm) 3.86 (d, J = 1.5 Hz, 2H), 6.9-7.1 (m, 2H) , 7.57 (dd, J = 8.8, 5.3 Hz, 1H), 9.76 (t, J = 1.5 Hz, 1H). 18.2 l-Bromo-4-fluoro-2- [2- (methoxymethoxy) ethyl] benzene (22a) To a solution of 21a (3.60 g, 16.6 mmol) in methanol (40 mL) was added sodium borohydride (640 mg, 16.6 mmol) at 0 ° C, and the mixture was stirred at room temperature for 1 hour. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. To the residue were added dichloromethane (50 mL), diisopropylethylamine (3.5 mL, 20 mmol) and methyl chloromethyl ether (1.5 mL, 20 mmol) at 0 ° C, and the reaction mixture was stirred at room temperature overnight. Water was added, and the mixture was extracted with chloroform. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (hexane / ethyl acetate 15: 1) to give 22a (2.99 g, 2 steps, 68%) as a colorless oil: XH NMR (300 MHz, CDC13) d (ppm) 3.04 (t, J = 6.7 Hz, 2H), 3.31 (s, 3H), 3.77 (t, J = 6.7 Hz, 2H) , 4.62 (s, 2H), 6.82 (td, J = 8.2, 3.2 Hz, 1H), 7.04 (dd, J = 9.4, 2.9 Hz, 1H), 7.48 (dd, J = 8.8, 5.3 Hz, 1H). 18.3 l-Bromo-2- [2- (methoxymethoxy) ethyl] benzene (22b) This compound was synthesized from 21b in a manner similar to 22a and used for the next step without purification. 18.4 6-Fluoro-l-phenyl-1,2,3,4-tetrahydro-2, 1-benzoxazole (23a) This compound was synthesized from 22a and 7a in a manner similar to compound 9f: colorless oil; 1 H NMR (300 MHz, CDC13) d (ppm) 3.02 (t, J = 6.1 Hz, 2H), 4.34 (t, J = 6.1 Hz, 2H), 6.9-7.1 (m, 2H), 7.4-7.6 (m , 3H), 7.8-7.9 (m, 3H); ESI-MS m / z 227 (M + H) +; purity by HPLC 95.3%; Analyzed (Ci4H12BFO · 0.1H20) C, H. 18.5 1-Phenyl-1,2,4,4-tetrahydro-2, 1-benzoxaborine (23b) This compound was synthesized from 22b and 7a in a manner similar to the compound 9f: colorless oil; 1 H NMR (300 MHz, DMSO-d 6) d (ppm) 2.94 (t, J = 5.9 Hz, 2H), 4.21 (t, J = 5.9 Hz, 2H), 7.28 (t, J = 7.9 Hz, 2H), 7.3-7.5 (m, 4H), 7.66 (d, J = 7.0 Hz, 1H), 7.75 (d, J = 7.6 Hz, 2H); ESI-MS m / z not observed; purity by HPLC 96.0%; Analyzed (Ci4Hi3BO) C, H. 18. 6-Fluoro-l-hydroxy-l, 2,3,4-tetrahydro-2, 1-benzoxaborine (24) This compound was synthesized from 22a in a manner similar to compound 19b. Column chromatography on silica gel (hexane / ethyl acetate 2: 1) followed by titration with pentane 24 as a white powder; p.f. 77-82 ° C; NMR XH (300 MHz, D SO-d6) d (ppm) 2.86 (t, J-5.9 Hz, 2H), 4.04 (t, J = 5.9 Hz, 2H), 7.0-7.1 (m, 2H), 7.69 ( dd, J = 8.2, 7.2 Hz, 1H), 8.47 (s, 1H); ESI-MS m / z 165 (M-H) ~; purity by HPLC 99.0%; Analyzed (C8H8BF02) C, H. Example 19 Formation of Ethylene Glycol Boronate Ester (3, T = none) General Procedure Boronic acid was dissolved in dry THF, dry toluene or dry diethyl ether (approximately 10 mL / g) under nitrogen. Ethylene glycol (1 mole equivalent) was added to the reaction and the reaction was heated to reflux for 1 to 4 hours. The reaction was cooled to room temperature and the solvent was removed under reduced pressure leaving the ethylene glycol ester as an oil or a solid. In cases where an oil or a solid was obtained which was dissolved in hexane, dry hexane was added and removed under reduced pressure. The product was then placed under high vacuum for several hours. In cases where a solid was obtained that did not dissolve in hexane, the solid was collected by filtration and washed with cold hexane. Ethylene glycol ester of 3-cyano-phenylboronic acid (3a) 3-Cyanophenyl-boronic acid (1 g, 6.8 mmol) was dissolved in dry THF (10 mL) under nitrogen. Ethylene glycol (379 μl, 422 mg, 6.8 mmol) was added and the reaction was heated to reflux for 4 hours then cooled to room temperature. THF was removed by rotary evaporator to give a white solid. Cold hexane was added and the product was collected by filtration to give a white solid (1.18 g, quantitative yield). RN XH (300.058 MHz, DMSO-d6) d ppm 7.92-8.01 (3H, m), 7.50-7.64 (1H, m), 4.35 (4H, s) Ethylene glycol ester of thiophene-3-boronic acid (3b) dissolved thiophene-3-boronic acid (1 g, 7.8 mmol) in dry THF (10 mL) under nitrogen. Ethylene glycol (435 uL, 484 mg, 7.8 mmol) was added and the reaction was heated to reflux for 1 hour then cooled to room temperature. THF was removed by rotary evaporator to give a white solid. Hexane was added, dissolving the solid and stirring by rotary evaporation. The product was placed under high vacuum to produce a light brown solid (1.17 g, 97%). NMR ¾ (300.058 MHZ, CDC13) 5ppm 7.93 (1H, s), 7.3-7.4 (2H, m), 4.35 (4H, s). Ethylene glycol ester of 3-fluorophenylboronic acid (3c) A mixture of 32-fluorophenylboronic acid (7.00 g, 50.0 mmol) and ethylene glycol (2.8) was heated. mL, 50 mmol) in toluene (200 mL) under reflux for 3 hours under Dean-Stark conditions. The solvent was removed under reduced pressure to give 3-fluorophenylboronic acid ethylene glycol ester (7.57 g, 91%). Formation of Borinic Acid (6) Not Symmetrical from Ethylene Glycol Ester of Boronic Acid Procedure A General: Method of Grignard Ethylene glycol ester of boronic acid was dissolved in dry THF (10-20 mL / g) under nitrogen. The solution was cooled to -78 ° C in an acetone / dry ice bath or at 0 ° C in an ice / water bath. Grignard reagent (0.95 to 1.2 molar equivalent) was added dropwise to the cooled solution. The reaction was warmed to room temperature and stirred for 3-18. 6N HC1 (2 mL / g) was added and the solvent was removed under reduced pressure. The product was extracted into diethyl ether (40 mL / g) and washed with water (3 times equal volume). The organic layer was dried (MgSO 4), filtered and the solvent was removed by rotary evaporation to give the crude product, which was either purified by column chromatography or taken in the next step without purification. Alternative treatment: if the borinic acid product contained a basic group such as an amine or pyridine, then after stirring at room temperature for 3-18 hours, water (2 mL / g) was added and the pH adjusted to 5- 8 The product was extracted in diethyl ether to ethyl acetate or THF up to three times (40 mL / g). The organic layer was dried (MgSO4), filtered and the solvent was removed by rotary evaporation to give the crude product, which was either purified by column chromatography or taken in the next step without purification. (-cyanophenyl) (3-fluorophenyl) boronic acid (6a) 4-cyanophenylboronic acid ethylene glycol ester (500 mg, 2.89 mmol) was dissolved in dry THF under nitrogen. The solution was cooled to -78 ° C in an acetone / dry ice bath and 3-flurophenylmagnesium bromide (1M in THF) (2.74 mL, 2.74 mmol, 0.95 molar equivalent) was added dropwise to the cold solution. The reaction was allowed to slowly warm to room temperature and was stirred for 18 hours. 6N HC1 (1 mL) was added to the reaction causing a cloudy appearance and the solvent was removed using a rotary evaporator. The product was extracted into diethyl ether (20 mL) and washed with water (3x20 mL). The organic layer was dried (MgSO4), filtered and the solvent was removed using a rotary evaporator to produce the product as an oily solid. This was taken in the next step without purification. General Procedure B: (Hetero) aryl lithium methodology The (hetero) aryl bromide or iodide was dissolved in dry THF (20-30 mL / g) under nitrogen and degassed. The solution was cooled to -78 ° C in an acetone / dry ice bath and n-, sec-, or tert-butyllithium in THF or other solvent (1.2-2.4 molar equivalents) was added to the cooled solution dropwise (generally causing the solution to turn bright yellow). The ethylene glycol ester of boronic acid (1 molar equivalent) was dissolved in dry THF or diethyl ether (2-10 mL / g) under nitrogen. The ethylene glycol ester of boronic acid in THF was added dropwise to the cooled solution of aryl lithium (generally causing the solution to turn pale yellow). The reaction was warmed to room temperature and stirred for 1-18 hours. 6N HC1 (2-4 mL / g) was added and the solvent was removed under reduced vacuum. The product was extracted into diethyl ether (40 mL / g) and washed with water (3 times equal volume). The organic layer was dried (MgSO 4), filtered and the solvent was removed by rotary evaporation to give the crude product, which was either purified by column chromatography or taken in the next step without purification. The alternative treatment: if the borinic acid product contained a basic group such as an amine or pyridine, then after stirring at room temperature for 3-18 hours, water (2 mL / g) was added and the pH adjusted to 5. -8. The product was extracted into diethyl ether to ethyl acetate or THF up to three times (40 mL / g) and washed with water (3 times equal volume). The organic layer was dried (MgSO 4), filtered and the solvent was removed by rotary evaporation to give the crude product, which was either purified by column chromatography or taken in the next step without purification. (3-Thienyl) (3-chlorophenyl) borinic acid (6b) 3-Chloro-bromobenzene (447 pL, 728 mg, 3.8 mmol) was dissolved in dry THF (15 mL) under nitrogen. The solution was degassed and cooled to -78 C in an acetone / dry ice bath. Tert-butyl-lithium (1.7 M in THF) (4.47 mL, 7.6 mmol, 2 molar equivalent) was added to the cooled solution drop by drop, causing the solution to take on an intense yellow color. The solution was stirred at -78 ° C while the ethylene glycol ester of 3-thiopheneboronic acid (586 mg) was dissolved in dry diethyl ether (1 mL). The boronic ester solution was then added dropwise to the cooled solution causing the color to turn pale yellow. The reaction was warmed to room temperature and stirred for 18 hours. 6N HC1 (2 mL) was added and the reaction was stirred for 1 hour. The solvent was removed using a rotary evaporator. The product was extracted into diethyl ether (10 mL) and washed with water (2 times 10 mL). The organic layer was dried (MgSO4). It was filtered and the solvent was removed using a rotary evaporator to produce the crude product as an orange oil. The product was purified by column chromatography using silica gel and hexane: ethyl acetate 5: 1 as eluent to give the crude product as a clear oil (614 mg, 73%): (3-Chlorophenyl) vinylboric acid (6c) This was prepared by a similar process as described for 6b by the reaction of ethylene glycol ester of 3-cyanophenylboronic acid with vinyl lithium. (3-Fluoro-chlorophenyl) ethylborinic acid (6d) This was prepared by a similar process as described for 6b by the reaction of ethylene glycol ester of 3-fluoro-5-chlorophenylboronic acid with ethynyl lithium. (4-Methyl-3-chlorophenyl) (2-thienyl) boric acid (6e) This was prepared by a similar process as described for 6b by the reaction of ethylene glycol ester of 2-thienylboronic acid with 4-methyl-3- chlorophenyl-lithium. (4-Cyanophenyl) ethynylborinic acid (6f) This was prepared by a similar process as described for 6b by the reaction of ethylene glycol ester of 4-cyanophenylboronic acid with ethynyl lithium. (3-Fluorophenyl) cyclopropylborinic acid (6g) This was prepared by a similar process as described for 6b by the reaction of ethylene glycol ester of 3-fluorophenylboronic acid with cyclopropyl-lithium. (3-Thienyl) methylborinic acid (6h) This was prepared by a similar process as described for 6b by the reaction of ethylene glycol ester of 3-thienylboronic acid with methyl lithium. (4-Pyridyl) phenylborinic acid (6i) This was prepared by a similar process as described for 6b by the reaction of ethylene glycol ester of phenylboronic acid with 4-pyridyllithium. (3-Cyanophenyl) (2-fluorophenyl) boric acid (6j) This was prepared by a similar process as described for 6b by the reaction of ethylene glycol ester of 3-cyanophenylboronic acid with 2-fluorophenyllithium. 4- (Dimethylaminomethyl) phenyl-3-fluorophenyl-boronic acid (6k) Secon-butyllithium (1.4 M in cyclohexane, 6. 0 mL) was added to a solution of N, -dimethyl-4-bromobenzylamine (1.50 g, 7.00 mmol) in THF (14 mL) at -78 ° C under nitrogen atmosphere and the mixture was stirred for 15 minutes. Ethylene glycol ester of 3-fluorophenylboronic acid (1.16 g, 7.00 mmol) in THF (7 mL) was added. The reaction was allowed to warm to room temperature and was stirred for 1 hour. Water was added and the mixture was washed with ether. The pH was adjusted to 8 with 1M hydrochloric acid. The mixture was extracted with ethyl acetate twice, the organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give borinic acid (890 mg, 49%). Formation of Symmetric Borinic Acid (5) by Reaction of Organometallic with Trialkyl Borates Bis (-chlorophenyl) boronic acid (a) (Procedure C) A cold solution (-78 ° C) of trimethyl borate (0.37 mL) in dry tetrahydrofuran (THF, 25 mL) was treated twice with 4-chlorophenylmagnesium bromide (6.75 mL, 1M solution in ether). The reaction mixture was stirred at -78 ° C for 1 hour and then stirred for 18 hours at room temperature. The solvent was removed under reduced pressure. The resulting residue was stirred with 100 mL of ether and 15 mL of 6N hydrochloric acid. The organic layer was separated and the aqueous layer was extracted with ether (twice, 100 mL). The combined organic extracts were washed with brine and dried over anhydrous magnesium sulfate. The solvent was removed to give a light yellowish solid. The product is chromatographed on silica gel (Hexane: Ether = 1: 1) to give 420 mg of boric acid. NMR XH (400 MHz, CDC13) d: 5.84 (s, OH), 7.46 (d, 4H, Ar-H), 7.22 (d, 4H, Ar-H). Bis (3-chloro-4-methylphenyl) borinic acid (5b) In a similar manner as for 5a, the title compound was obtained from the reaction of 3-chloro-4-methylphenylmagnesium bromide with trimethyl borate. The product was obtained by chromatography on silica gel. Bis (3-fluoro-4-methylphenyl) boric acid (5c) In a similar manner as for 5a, the title compound was obtained from the reaction of 3-f luoro-4-methylphenithithium bromide with trimethyl borate. The product was obtained by chromatography on silica gel.

Bis (3-chloro-4-methoxyphenyl) boric acid (5d) In a similar manner as for 5a, the title compound was obtained from the reaction of 3-chloro-4-methoxyphenyllithium with trimethyl borate. The product was obtained by chromatography on silica gel. Bis (3-fluoro-4-methoxyphenyl) boric acid (5e) In a similar manner as for 5a, the title compound was obtained from the reaction of 3-fluoro-4-methoxyphenyllithium with trimethyl borate. The product was obtained by chromatography on silica gel. Formation of Non-Symmetric Borinic Acids (6) by Reaction of Organometallic with alkyl (or aryl or alkenyl) dialcoxyborane (4-Chlorophenyl) methyl-borinic acid (6m) (Procedure D) To 4-chlorophenylmagnesium bromide (5.5 mL, solution M in ether) at -78 ° C, di (isopropoxy) methylborane (1 ml, 0.78 g) was added dropwise by syringe. The reaction mixture was stirred at -78 ° C for 1 hour and then stirred overnight at room temperature. The reaction mixture was treated dropwise with 100 ml of ether and 15 ml of 6 N hydrochloric acid, and stirred for 1 hour. The organic layer was separated and the aqueous layer was extracted with ether (2X100 mL). The combined organic extract was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give 1.1 g of oil. The 1H NMR of product was consistent for (4-chlorophenyl) methylborinic acid. (4-Fluorophenyl) borinic acid (6n) In a similar manner as for 6m, the title compound was obtained from the reaction of 4-fluorophenylmagnesium bromide with di (isopropoxy) methylborane. The product was obtained by chromatography on silica gel. (4-Biphenyl) methylborinic acid (6o) In a similar manner as for 6m, the title compound was obtained from the reaction of 4-biphenyllithium with di (isopropoxy) methylborane. The product was obtained by chromatography on silica gel. (3-Chloro-4-methylphenyl) methylborinic acid (6p) In a similar manner as for 6m, the title compound was obtained from the reaction of 3-chloro-4-methylphenyllithium with di (isopropoxy) methylborane. The product was obtained by chromatography on silica gel. (3-Chloro-4-methoxyphenyl) -methylborinic acid (6q) In a similar manner as for 6m, the title compound was obtained from the reaction of 3-chloro-4-methoxyphenyllithium with di (isopropoxy) methylborane. The product was obtained by chromatography on silica gel. (4-dimethylaminophenyl) methylborinic acid (6r) In a similar way as for 6m, the title compound was obtained from the reaction of 4-dimethylaminophenylthio with di (isopropoxy) methylborane. The product was obtained by chromatography on silica gel. (3-pyridyl) borinic acid (6s) Isopropylmagnesium chloride (2.0 M in THF) (5.0 mL) was added, 10 mmol) was added to a solution of 3-bromopyridine (1.60 g, 10.0 m mol) in THF (15 mL) under nitrogen atmosphere at room temperature and the mixture was stirred for 1 hour. Dibutyl phenylboronic acid ester (3.4 mL) was added to the reaction dropwise and the mixture was stirred at room temperature for 18 hours. Water was added and the pH adjusted to 7 with hydrochloric acid 1. The mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give the title compound (1.04 g, 78%). (3-Chloro-4-dimethylaminophenyl) vinylborinic acid (6t) In a similar manner as for 6s, the title compound was obtained from the reaction of 3-chloro-4-dimethylaminophenyllithium with dibutyl ester of vinylboronic acid. The product was obtained by chromatography on silica gel. Borinic Acid-Alkyl Alcohol Derivatives Bis (3-chlorophenyl) borinic acid 4- (hydroxyethyl) imidazole ester (121) To a solution of bis (3-chlorophenyl) borinic acid (0.4 g, 1428 mmol) in ethanol (10 mL), 4- (hydroxyethyl) imidazole hydrochloride (0.191 g, 1428 mmol), and sodium carbonate (0.180 g, 2143 mmol) were added and the reaction mixture was stirred at room temperature for 18 hours. The salt was removed by filtration. The filtrate was concentrated and treated with hexane to give the product as a solid and collected by filtration. (450 mg, 84.9% yield). H NMR (CD3OD) d (ppm) 2.92 (t, 2H), 3.82 (t, 2H), 7.0-7.2 (m, 9H), 7.90 (s, 1H); (ES ") (m / z) 343.11, MFCi7Hi5BCl2N20 4- (Hydroxymethyl) imidazole ester of bis (4-chlorophenyl) boric acid (126) In a similar manner as in Example 121, the title compound was obtained from of the reaction of bis (4-chlorophenyl) boric acid and 4- (hydroxymethyl) imidazole hydrochloride The product was obtained as white crystals (ES ") (m / z) 328.79, MFC16H13BCI2N-2O Ester of l-benzyl 4- (Hydroxymethyl) -imidazole of bis (3-chloro-4-methylphenyl) boric acid (127) To a solution of l-benzyl-4- (hydroxymethyl) imidazole (96 mg, 0.521 mmol) in methanol (5 ml) , bis (3-chloro-4-methylphenyl) borinic acid (121 mg, 0.521 mmol) was added and the reaction mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure and the residue was treated with hexane to give a solid. The product was isolated by filtration and washed with hexane to give the product (193 mg, 83%). NMR XH (400 MHz, CDC13) d: 2.3 (s, H, 2 times CH3), 4.8 (brs, 2H, CH2), 5.1 (brs, 2H, CH2), 6.9-7.4 (complex, 13H, Ar-H ); MS (ES +) (m / z) 448.78, F C25H23BCli2N20. Ester of l-methyl-2- (hydroxymethyl) -imidazole of bis (3-chloro-4-methylphenyl) borinic acid (128) In a similar manner as in Example 127, the title compound was obtained from the reaction of bis (3-chloro-4-methylphenyl) boronic acid with 1-methyl-2- (hydroxymethyl) imidazole hydrochloride. The product was obtained as white crystals. (ES +) (m / z) 372.82, MF Ci9H2iBCl2N20. Ester of l-ethyl-2- (hydroxymethyl) -imidazole of bis (3-chloro-4-methylphenyl) boric acid (129) In a similar manner as in Example 127, the title compound was obtained from the reaction of bis (3-chloro-4-methylphenyl) boronic acid with 1-ethyl-2- (hydroxymethyl) imidazole hydrochloride. The product was obtained as white crystals. (ES +) (m / z) 386.83, MF C20H23BCI2N2O. Ester of l-methyl-4- (hydroxymethyl) -imidazole of bis (3-chloro-4-methylphenyl) borinic acid (130) In a similar manner as in Example 127, the title compound was obtained from the reaction of bis (3-chloro-4-methyl-phenyl) boric acid with hydrochloride of 1-methyl ti-4 - (hi drox i -me ti 1) imide zo 1. The product was obtained as white crystals.

(ES +) (m / z) 372.82, MF C19H2iBCl2N20. 2-pyridylethanol of bis (3-chloro-4-methylphenyl) borinic acid (131) In a similar manner as in Example 121, the title compound was obtained from the reaction of bis (3-chloro-4-) acid methylphenyl) borinic acid with 2-pyridylethanol. The product was obtained as white crystals. (ES +) (m / z) 383.84, MF C21H20BCI2NO. Derivatives of Hydroxyquinoline Ester of 5-cyano-8-hydroxyquinoline of bis (3-chlorophenyl) borinic acid (19) To a solution of bis (3-chlorophenyl) borinic acid (0.25 g) in ethanol (5 ml) and water (2) mi) was added-cyano-8-hydroxyquinoline (0.15 g). The solution was stirred at room temperature for 21 hours. A yellow solid precipitate formed which was collected by filtration and washed with cold ethanol. The product was obtained as yellow crystals. 1 H NMR (DMSO) d (ppm) 7.24-7.35 (m, 8H), 7.38 (d, 1H), 8.18 (dd, 1H), 8.40 (d, 1H), 8.86 (d, 1H), 9.50 (d, 1 HOUR) . 8-Hydroxyquinoline ester of (3-chlorophenyl) (2-thienyl) borinic acid (36) To a solution of (3-chlorophenyl) (2-thienyl) borinic acid (1.5 g) in ethanol (2 ml) was added 8 -hydroxyquinoline (0.77 g) in hot ethanol (2 ml). The reaction was heated to reflux and cooled to room temperature. A yellow solid precipitated. The mixture cooled on ice, the solid was collected by filtration and washed with cold ethanol. The product was obtained as a yellow solid (1.01 g). 1N-NMR (400 MHz, CDC13) d: (ppm) 6.98-7.06 (m, 2H), 7.19-7.26 (m, 3H), 7.38-7.50 (m, 4H), 7.71 (t, 1H), 7.91 (dd) , 1H), 8.80 (d, 1H), 9.18 (d, 1H); (ESI +) (m / z) 350.1, MF C19H13BC INOS. 8-hydroxyquinoline ester of (2-thienyl) methylborinic acid (26) In a similar manner to Example 36, the title compound was obtained from the reaction of (2-thienyl) methylborinic acid with 8-hydroxyquinoline. The product was obtained as yellow crystals. 8-Hydroxyquinoline ester of (3-cyanophenyl) vinylborinic acid (40) In a similar manner to Example 36, the title compound was obtained from the reaction of (3-cyanophenyl) vinylborinic acid with 8-hydroxyquinoline. The product was obtained as yellow crystals. (ESI +) (m / z) 285.1, MF Ci8Hi3BN20. 8-hydroxyquinoline ester of (2-chlorophenyl) ethynylborinic acid (43) In a similar manner to Example 36, the title compound was obtained from the reaction of (2-chlorophenyl) ethynylborinic acid with 8-hydroxyquinoline. The product was obtained as yellow crystals. (ESI +) (m / z) 292. 1, F Ci7HnBClNO. 8-Hydroxyquinoline of bis (ethynyl) borinic acid (44) In a similar manner to Example 36, the title compound was obtained from the reaction of bis (ethynyl) boric acid with 8-hydroxyquinoline. The product was obtained as light yellow crystals. (ESI +) (m / z) 206.1, MF Ci3Hi8BNO. 8-Hydroquinoline ester of (3-fluorophenyl) cyclopropylborinic acid (70) In a similar manner to Example 36, the title compound was obtained from the reaction of (3-fluorophenyl) cyclopropylborinic acid with 8-hydroxyquinoline. The product was obtained as light yellow crystals. (ESI ") (m / z) 291.05, MF Ci8H15BFNO. 8-hydroxyquinoline ester of (3-pyridyl) vinylborinic acid (99) A solution of (3-pyridyl) vinyl borinic acid (1.04 g, 7.82 mmol) and 8-hydroxyquinoline (961 mg, 6.63 mmol) in ethanol was stirred at 40 ° C for 20 minutes. The solvent was removed under reduced pressure and the residue was crystallized from diethyl ether / diisopropyl ether / hexane to give the title product (99) as light yellow powder (355 mg, 21%). XH NMR (DMS06) d: (ppm) 5.23 (dd, 1H), 5.46 (dd, 1H), 6.43 (dd, 1H), 7.14 (d, 1H), 7.19 (dd, 1H), 7.41 (d, 1H) ), 7.6-7.8 (m, 2H), 7.88 (dd, 1H), 8.35 (dd, 1H), 8.57 (s, 1H), 8.76 (d, 1H), 9. 00 (d, 1H); ESI + (m / z) 261 MF Ci6Hi3BN20. Ester of (4- (dimethylaminomethyl) phenyl) (3-fluorophenyl) borinic acid (8-hydroxyquinoline) (100) In a similar manner as in Example 99, the title compound was obtained from the reaction of (dimethylaminomethyl) phenyl) (3-fluorophenyl) borinic acid with 8-hydroxyquinoline. The product was obtained as a light yellow powder. ESI + (m / z) 385 MF C24H22B FN2O. Derivatives of 3-Hydroxy-picnic acid Ester of bis (3-chloro-4-methylphenyl) borinic acid 3-hydroxy-piolinate (111) Bis (3-chloro-4-methylphenyl) boric acid (14.6 g) was dissolved in ethanol (120 mL) ) and heated to reflux. 3-Hydroxypicolinic acid (5.83 g) was added in portions to the hot solution. The reaction was stirred at reflux for 15 minutes then the addition of the last portion of 3-hydroxypicolinic acid was added and then cooled to room temperature. The reaction was concentrated by removal of some ethanol. The solid was removed by filtration. In the recrystallization of the ethanol gave the title product as white crystals (13.4 g), P.F. = 165.0-166.5 ° C. Example 20 Anti-inflammatory data for 3-hydroxypyridine-2-carbonyloxy-bis (3-chloro-4-methylphenyl) borane Pro-inflammatory cytokines: THP-1, LPS a 1 cells / 238 mg / mL, 24 hr TNF-a: 2.7 μ ?; IL-? ß: 1.0 μ ?; IL-6: 5.3 μ ?; IL-8: 9. 6 μ? TH1 cytokines: PBMC, PHA at 20 mg / mL, 24 h IFN-g: > 25 μ ?; IL-2: > 25 μ? TH2 cytokines: PBMC, PHA at 20 mg / mL, 24 h IL-4: > 25 μ ?; IL-5: 9.3 μ ?; IL-10: 14.5 μ ?; IL-13: > 10 μ? Regulatory cytokine: PBMC; PHA at 10 mg / mL, 24 h IL-3: > 10 μ ?. EXAMPLE 21 Toothpaste Formulation Containing Hydrated Calcium Sulfate and Approximately 0.5% by Weight of 3-Hydroxypicolinate 3-hydroxypyridine-2-carbonyl-bis (3-chloro-4-methylphenyl) -borane (bis) ester (3-Chloro-4-methylphenyl) boronic) A toothpaste formulation according to the present invention was prepared as follows: To an appropriate measuring vessel are added 6 mL of grape oil, 2 mL of citrus oil, 2 mL of sweet oranges oil, 2 mL of peppermint oil, and 2 mL of eucalyptus oil, and the flavor oils are mixed at room temperature, then thick liquid paraffin is added [Food Grade] (also known as mineral oil). ) in a enough to bring the total volume of the mixture to 100 mL. The oil component is mixed to form a homogeneous solution. This is the base flavor oil component for use in the toothpaste examples described herein. To 30 g of fine powder gypsum (calcium sulfate dihydrate, pure for the food production industry), 0.2 g of 3-hydroxypyridine-2-carbonyl-bis (3-chloro-4-methylphenyl) borane ( bis (3-chloro-4-methylphenyl) boronic acid 3-hydroxy-piolinate ester) as a solid, dry powder. The two solids are mixed to form a homogeneous solid, and then 12 g of the flavor oil component of the above is added. The composition of the powders and oils are mixed together to form a fine paste. The dough is then packed in a tube. EXAMPLE 22 Toothpaste Formulation Containing Calcium Sulfate Dihydrate and Approximately 5.0% by Weight of 3-hydroxypyridine-2-carbonyl-bis (3-chloro-4-methylphenyl) borane (bis-3-hydroxy-piolinate ester) 3-chloro-4-methylphenyl) boronic) The paste composition in Example 21 is reformed, this time using 2.2 g of 3-hydroxypyridine-2-carbonyl-bis (3-chloro-4-methylphenyl) -borane (sodium ester). Bis (3-chloro-methylphenyl) boronic acid 3-hydroxy-piolinate, in the same manner, as described. The paste is formed into a thin paste, as before, and is packaged in a tube.

EXAMPLE 23 Toothpaste Formulation Containing Calcium Sulfate Dihydrate, Approximately 5.0% by weight of 3-hydroxypyridine-2-carbonyl-bis (3-chloro-4-methylphenyl) -borane (bis-3-hydroxy-piolinate ester) 3-chloro-4-methylphenyl) boronic), and Glycerin To 60 g of fine powdered gypsum (as in Example 21), 1.2 g of 3-hydroxypyridine-2-carbonyl-bis (3-chloro-4-) are added. methylphenyl) -borane (bis (3-chloro-4-methylphenyl) boronic acid 3-hydroxypicolinate ester) as a dry powder, and the two solids are mixed together to form a homogeneous powder. This solid powder is then mixed with 32 g of the oil component (as prepared in Example 21) for 30 minutes. It is a fine paste half liquid. To this paste is added 4 g of glycerin (available from numerous commercial sources), and mixing is continued for an additional 30 minutes. The product paste is packaged in aluminum tubes and is ready for use. EXAMPLE 24 Oral Wash Containing Approximately .5% by Weight of 3-hydroxypyridine-2-carbonyl-bis (3-chloro-4-methylphenyl) -borane (3-hydroxy-piolinate ester of bis (3-chloro-4-methylphenyl) acid ) boronic) A buccal wash is prepared in a conventional manner to the following composition: % p / p 70% sorbitol solution (non-crystalline) 5 Ethanol 96% BP (% by volume) 7 Saccharin sodium crystal BP (76% Sac) 0.02 Hydrogenated castor oil with 0.15 polyethylene glycol 40 (available under the name commercial Croduret 40 ET 0080 DF) Polyoxyethylene sorbitan monolaurate 0.15 (available under the trade name Tween 20) Sodium fluoride BP 0.05 Sodium benzoate BP 0.1 Blue 12401 Anst 0.0006 Yellow 2G Anst 0.00055 Bouthwash mouthfeel BP 1 (% in 0.1 volume) Compound containing boron (3- 0.5 hydroxypyridine-2-carbonyl-bis (3-chloro-4-methylphenyl) -borane (bis (3-chloro-4-methylphenyl) boronic acid 3-hydroxypicolinate ester Purified water Rest 100.0 total The mouthwash is made by first mixing together, at room temperature, the ethanol and water, after which the additional components are mixed with the aqueous alcoholic medium, the surfactants, flavor, humectants, copolymer, and boron-containing compound that are in the formula. The finished mouthwash is then filtered, if necessary. Example 25 Toothpaste Containing Approximately .3% by Weight of 3-hydroxypyridine-2-carbonyl-bis (3-chloro-4-methylphenyl) -borane (bis (3-chloro-4-methylphenyl) boronic acid 3-hydroxy-piolinate ester A toothpaste is prepared in a conventional manner to the following composition:% by weight Precipitated silica 25.0 Silica gel 2.0 Sorbitol 20.0 Propylene glycol 2.5 Sodium carboxymethylcellulose 1.0 Lauryl-diethanolamide 1.0 Sodium lauryl sulfate 1.5 Sodium lauroyl sarcosinate 0.3 Saccharin sodium 0.1 ethyl p-oxybenzoate 0.1 Compound containing boron (3-hydroxypyridine-0.3) 2-carbonyl-bis (3-chloro-4-methylphenyl) -borane (bis (3-chloro-4-methylphenyl) boronic acid 3-hydroxy-piolinate ester)) Stagnant gluconate 0.3 Gelatin 0.2 Flavor 0.8 Purified water Total rest 100.0 g_ The compounds are mixed at room temperature to form a homogeneous fine paste The paste is then packed into a tube Example 26 MIC test All MIC test followed the guidelines of the National Committee for Clinical Laboratory Standards (NCCLS) for antimicrobial testing of yeasts (M27-A2 NCCLS) and filamentous fungi (Pfaller et al., NCCLS publication M38-A-Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi; Approved Standard, Wayne, PA: NCCLS; 2002 (Vol. 22, No. 16) except for the Malassezia species that was incubated in a urea broth (Nakamura et al., Antimicrobial Agents and Chemotherapy, 2000, 44 (8), p 2185-2186) .The results of the MIC test are given in Tables 1A-1B The compounds of this invention n are evaluated for antibacterial activity as per the guidelines and processes prescribed by the National Committee for Clinical Laboratory Standards (NCCLS) (cf., NCCLS Document M7-A3, 1993 Antimicrobial Susceptibility Testing). Protocol for MIC Determination A useful protocol for the determination of MIC is as follows: 1. Approximately 2.5 mg of the compounds to be tested were weighed in cryo-flasks. 2. Concentrated solutions of 5 mg / mL were prepared by adding DMSO to the samples, accordingly. 3. Working solutions of 256 μg / mL were prepared by using the concentrated solutions of 5 mg / mL and adding sterile distilled water, accordingly. 4. The automated Beckman 2000 workstation was programmed to load plates of 96 concavities with broth and compounds as follows: 100 μ ?, of the appropriate broth were added to columns 1-11 200 μ ?. of the appropriate broth were added to the column 12 100 μ? > of compounds in the working solution of 256 μg / mL were added to column 1 (one compound per row) Serial two-fold dilutions of column 1 to 10 were made. Column 11 served as the growth control . The panel of 10 organisms was placed in a plate of stock bottles stored at -80 ° C and incubated for 24 hours at 34 ° C. The organisms were then subcultured and incubated for 24 hours at 34 ° C. The inocula were prepared first in sterile distilled water with an absorbance target of 0.09-0.11 at 620 nm wavelength. A dilution was made. { Fraction (1/100)} in the appropriate broth 100 μL of the broth with organism was added to columns 1-11 Column 12 served as blank control 6. Plates of 96 finished concavities were incubated for 24 hours at 34 ° C. The 96-well plates were then read using a Beckman Automated Plate Reader at a wavelength of 650 nm. MIC was determined through calculations comprising growth control (column 11) and blank control (column 12). Protocol for the Determination of In Vitro Antifungal MIC A useful protocol for the determination of antifungal activity is described below.

Preparation The media were prepared 1-2 weeks before the start of the experiment. The media was stored in a cold room (4 ° C) before use. Dextrose-Agar Plates of Sabouraud: 1. Add 65 g of Dextrose-Agar Sabouraud's medium powder in 1 L of dH20 with gentle agitation. 2. Autoclave at 121 ° C and 1.54 kg / cm2 (22 lb / in2) for 15 minutes 3. Allow the medium to cool to approximately 50 ° C. 4. Pour the medium into sterile petri dishes of 100 X 15 mm with 20 mL aliquots. RPMI 1640 Broth + MOPS: 1. Add 1 pack of RPMI powder medium to 1 L of dH20 (15 ° C-30 ° C) with gentle agitation 2. Add 2 g of NaHC03 3. Add 34.5 g of MOPS 4. Adjust the pH to 7.0 using NaOH or HC1 5. Sterilize with membrane filtration (filter 0.22 micron cellulose acetate). Sterile saline solution (0.9%) 1. Dissolve 9 g of NaCl to 1 L of dH20 2. Autoclave at 121 ° C and 1.54 kg / cm2 (22 lb / in2) for 15 minutes sterile dH20 1. Autoclave dH20 at 121 ° C and 1.54 kg / cm2 (22 lb / in2) for 15 minutes Procedure 1. The panel of 10 orgms was placed in flask plates stored at -80 ° C (suspended in broth with 20% glycerol) and incubated at 37 ° C for 24 hours. The orgms were then subcultured and incubated at 37 ° C for 24 hours. These were used to prepare fresh inocula for Step 6. 2. Approximately 2.5 mg of the compounds to be tested are weighed in 2 mL cryo-flasks. Fluconazole, Amphotericin B and Itraconazole are tested as reference compounds. 3. Concentrated solutions of 5 mg / mL are prepared by adding DMSO to the samples, accordingly. Insoluble compounds with only vortex are portrayed with ultrasound. 4. Working solutions of 256 μg / mL are prepared by using the concentrated solutions of 5 mg / mL and by adding sterile distilled water. 5. 96-well plates are used for MIC determination. Each of the 8 rows can be used to test a different compound. Compounds are loaded into the first column and twice dilutions are made from column 1 to 10. Column 11 is a growth control (without compound) and column 12 is a blank control (without compound or orgm). The manual addition of broth and compounds is done as follows: 100 μL of RPMI broth + MOPS are added to columns 1-11 200 μL of RPMI broth + MOPS are added to column 12 100 μ ?, of compounds are added to Working solution of 256 μg / mL to column 1 (one compound per row) Serial dilutions are made twice from column 1 to 10 Column 11 serves as the growth control (medium + orgm only) 6. The Subcultivated orgms are used to prepare fresh inocula for testing in 96-well plates. Each plate of 96 concavities will test a different orgm. Colonies of sub-cultured orgms (Step 1) are used to prepare inocula with sterile saline. The objective is adjusted to 70-75% transmittance at a wavelength of 530 nm using a Novospec II spectrophotometer. A dilution is made. { fraction (1/1000)} in RPMI + MOPS broths 100 μ ?? of this broth with orgms are added to columns 1-11 (column 12 serves as blank control). 7. Plates of 96 finished concavities are incubated at 37 ° C for 24 hours. The 96-well plates are then read for absorbance at 650 nm wavelength using a Biomek Automated Plate Reader. Calculations The absorbance readings of the Biomek Automated Plate Reader are used to determine the percent inhibition for each test concavity. The formula used is as follows:% inhibition = [1- (ABStest-ABSbianco) / (ABS medium growth ~ ABSbianco)] X 100% ABStest: Absorbance of the test concavity ABSbianco: Absorbance of the blank concavity of the same row as the test concavity (column 12) ABS medium growth: Average absorbance of growth control concavities (column 11) The minimum inhibitory concentration (MIC) is found at the lowest concentration of the compound where the percent inhibition is greater than or equal to 80%. In this way, the invention provides antibiotics that are generically called complexes of borinic acid, more preferably derivatives of disubstituted borinic acids. All patents, patent applications, and other publications cited in this application are hereby incorporated by reference in their entirety.

Table 1A% inhibition Structure TNF-a IL-lb IFN-g IL-4 (lOuM) (lOuM) (lOuM) (lOuM) OH 100 67 100 76 OH 91 25 94 59 OH 86.5 34.9 95.2 59.7 CN OH 60 57.8 93 45 * cXX0JCrK ° » Table IB% inhibition Structure TNF-a IL-lb IFN-g IL-4 (lOuM) (lOuM) (lOuM) (lOuM) OH 16.8 8.1 11 -4.4 1 OH 15.2 -29.2 12 13.3 1 (Xo Table 2B Table 2C Table 2D Table 2E Table 2F Table 2G Table 2H Table 21 Table 2J Table 3A No. RJa Raa R10a Rlla R12a 1 - . 1 -CH2Ph F H H H 2 - . 2 -CH2Ph 'H F H H 3 - . 3 -CH2Ph H H F H 4 - . 4 -CH2Ph H H H F - . 5 -CH2Ph F F H H 6 -. 6 -CH2Ph H F F H 7 -. 7 -CH2Ph H H F F No. RJa Rya Rlua RIla R1a 3. 4 - . 34 -CH2Ph H F F NMeS (0) 2Ph 35 -CH2Ph F F F NMeS (0) 2Ph 36 -CH2Ph H -CH2OH H H 37 -. 37 -CH2Ph H H -CH2OH H Table 3B No. RJa Rya Riua Rlla R12a 75 -. 75 -CH2Ph F -NH2 H H 76 -. 76 -CH2Ph H -NH2 F H 77 -. 77 -CH2Ph H -NH2 H F 78 -. 78 -CH2Ph Cl -NH2 H H 79 -. 79 -CH2Ph H -NH2 Cl H 80 -. 80 -CH2Ph H -NH2 H Cl Table 3C No. R3a R9a R10a Rlla R12a 81 -. 81 -CH2Ph F H -NH2 H 82 -. 82 -CH2Ph H F -NH2 H 83 -. 83 -CH2Ph H H -NH2 F 84 -. 84 -CH2Ph Cl H -NH2 H 85 -. 85 -CH2Ph H Cl -NH2 H 86 -. 86 -CH2Ph H H -NH2 Cl 87 -. 87 -CH2Ph F H H -NH2 88 -. 88 -CH2Ph H F H -NH2 89 -. 89 -CH2Ph H H F -NH2 90 -. 90 -CH2Ph Cl H H -NH2 91 -. 91 -CH2Ph H Cl H -NH2 92 -. 92 -CH2Ph H H Cl -NH2 93 -. 93 -CH2Ph F -NH2 F H 94 -. 94 -CH2Ph H -NH2 F F 95 -. 95 -CH2Ph F -NH2 F F 96 -. 96 -CH2Ph -0 (4-CN-Ph) H H H 97 -. 97 -CH2Ph H -0 (4-CN-Ph) H H No. R3a RSa R10a Rlla R12a 98 -. 98 -CH2Ph H H -0 (4-CN-Ph) H 99 -. 99 -CH2Ph H H H -0 (4-CN-Ph) • 100-CH2Ph F -0 (4-CN-Ph) H H 101 -. 101 -CH2Ph H -0 (4-CN-Ph) F H 102 -. 102 -CH2Ph H -0 (4-CN-Ph) H F 103 -. 103 -CH2Ph F -0 (4-CN-Ph) F H 104 -. 104 -CH2Ph H -0 (4-CN-Ph) F F 105 -. 105 -CH2Ph F -0 (4-CN-Ph) F F 106 -. 106-CH2Ph 3- (phenylthio) -HHH lH-indol-1-yl 107 -CH2Ph H 3- (phenylthio) -HH lH-indol-1-yl 108 -CH2Ph HH 3- (phenylthio) -H lH-indol- 1- ilo 109 -CH2Ph HHH 3- (phenylthio) -lH-indol-1-yl 110 -. 110-CH2Ph F 3- (phenylthio) - H HH-indol-1-yl 111 -CH2Ph H 3- (phenylthio) - F H lH-indol-1-yl No. R3a R9a R10a Rlla R12a 112 -. 112-CH2Ph H 3- (phenylthio) - HF lH-indol-1-yl 113 -CH2Ph F 3- (phenylthio) - FH lH-indol-1- lyl 114 -CH2Ph H 3- (phenylthio) -FF lH-indole -1- ilo 115 -CH2Ph F 3- (phenylthio) - FF lH-indol-1-yl 3D Table No. RJa Ru »R1U. Rlla Rí a 116 -CH2Ph Dibenzylamino H H H 117 -CH2Ph H dibenzylamino H H 118 -CH2Ph H H Dibenzylamino H 119 -CH2Ph H H Dibenzylamino 120 -. 120-CH2Ph F Dibenzylamino HH 121-CH2Ph H Dibenzylamino FH 122 -CH2Ph H Dibenzylamino HF 123 -CH2Ph F Dibenzylamino FH 124 -CH2Ph H Dibenzylamino FF 125 -CH2Ph F Dibenzylamino FF 126 -CH2Ph -S (0) 2 (4-Cl- HHH Ph) 127 -CH2Ph H -S (0) 2 (4-C1- HH Ph) No. RJa R3a Rlua RiIa Ri-a 150 -. 150 -CH2Ph F -NHCH2Ph H H 151 -. 151 -CH2Ph H -NHCH2Ph F H 152 -. 152 -CH2Ph H -NHH2Ph H F 153 -. 153 -CH2Ph F -NHC¾Ph F H 154 -. 154 -CH2Ph H -NHCH2Ph F F 155 -. 155 -CH2Ph F -NHCH2Ph F F 156 Me F H H H 157 Me H F H H 158 Me H H F H Table 3E No. R3a R9a R10a Rlla R12a 159 Me H H H F 160 Me F F H H 161 Me H F F H 162 Me H H F F 163 Me F H F H 164 Me H F H F 165 Me F H H F 166 Me H F F F 167 Me F H F H 168 Me F F H F 169 Me F F F H 170 Me F F F F 171 Me -0CH2C (0) 0H H H H 172 Me H -0CH2C (0) 0H H H 173 Me H H H OCH2C (0) OH Table 3F No. RJa Rya Riua Rlla R1 a 243 Me H F H -NH2 Table 3G No. Ria Rya Riua Rila R12a 244 Me H H F -NH2 245 Me Cl H H -NH2 246 Me H l H -NH2 247 Me H H Cl -NH2 248 Me F -NH2 F H 249 Me H -NH2 F F 250 Me F -NH2 F F 251 Me -0 (4-CH-Ph) H H H 252 Me H -0 (4-CH-Ph) H H 253 Me H H -0 (4-CH-Ph) H 254 Me H H H -0 (4-CH-Ph) 255 Me F -0 (4-CH-Ph) H H 256 Me H -0 (4-CH-Ph) F H 257 Me H -0 (4-CH-Ph) H F 258 Me F -0 (4-CH-Ph) F H 259 Me H -0 (4-CH-Ph) F F 260 Me F -0 (4-CH-Ph) F F Table 3H notes that in relation to this date, the best method known to the applicant to carry out the aforementioned invention is that which is clear from the present description of the invention.

Claims (24)

1. CLAIMS Having described the invention as above, the content of the following claims is claimed as property: 1. Oral care composition, characterized in that it comprises a compound having a structure according to one of the following formulas: wherein B is boron, 0 is oxygen, R * and R ** is each independently selected from substituted or unsubstituted (Ci-C4) alkyl, substituted or unsubstituted (C3-C7) cycloalkyl, substituted or unsubstituted alkenyl, substituted alkynyl or unsubstituted, substituted or unsubstituted aralkyl, substituted or unsubstituted phenyl, and substituted or unsubstituted heteroaryl; z is 0 or 1 and when z is 1, A is CH, CR10 or N; D is N, CH, or CR12; E is H, OH, alkoxy or 2- (morpholino) ethoxy, C02H or C02alkyl; m = 0-2; r is 1 or 2, and wherein when r is 1, G is = 0 (oxygen with double bond) and when r is 2, each G is independently H, methyl, ethyl or propyl; R12 is selected from (CH2) k0H (where k = 1, 2 6 3), CH2NH2, CH2NH2-alkyl, CH2N (alkyl) 2, C02H, C02alkyl, CONH2, OH, alkoxy, aryloxy, SH, S-alkyl, S -aryl, S02N (alkyl) 2 S02NHalkyl, S02NH2, S02alkyl, S03H, SCF3, CN, halogen, CF3, N02, NH2, 2 ° -amino, 3 ° -amino, NH2S02 and C0NH2, and wherein J is CR10 or N; R9, R10 and R11 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, (CH2) n0H (n = 2 to 3), CH2NH2, CH2NHalkyl, CH2 (alkyl) 2, halogen, CHO, CH = N0H , C02H, C02-alkyl, S-alkyl, S02-alkyl, S-aryl, S02N (alkyl) 2, S02NHalkyl, S02NH2, NH2, alkoxy, CF3, SCF3, N02, S03H and OH, including salts thereof. An oral care composition according to claim 1, characterized in that the oral care composition is a member selected from a mouthwash, toothpaste, liquid whitener, chewing gum, film or Soluble strips, partially soluble or not soluble, cloth or wipe, implant, dental floss. An oral care composition according to claim 2, characterized in that the dentifrice is a selected member of a powder, delta paste or dental gel. 4. The oral care composition according to claim 1, characterized in that the compound is present in a therapeutically effective amount. 5. The oral care composition according to claim 1, characterized in that the compound is present in an amount of about 0.1% w / w to about 5% w / w. 6. The oral care composition according to claim 1, characterized in that the compound is present in an amount of about 0.3% w / w to about 0.6% w / w. 7. Oral care composition according to claim 2, characterized in that the compound has a structure according to where m is 0. 8. Oral care composition according to claim 2, characterized in that the compound has a structure according to 9. Oral care composition according to claim 7, characterized in that E is OH, R9 is H and R * and R ** is each independently selected from substituted or unsubstituted phenyl. The oral care composition according to claim 9, characterized in that R * and R ** are each independently selected from 4-alkyl, 3-halogen-phenyl and 4-halogen, 3-alkyl-phenyl. 11. Oral care composition according to claim 10, characterized in that R * and R ** are 4-methyl, 3-chlorophenyl. 12. Oral care composition according to claim 11, characterized in that the compound is present in an amount of about 0.3% w / w to about 0.6% w / w. 13. Method to kill a microorganism or to inhibit the growth of a microorganism, characterized in that it comprises contacting the microorganism with a therapeutically effective amount of a compound having a structure according to one of the following formulas: wherein B is boron, O is oxygen, R * and R ** are each independently selected from substituted or unsubstituted (C 1 -C 4) alkyl, substituted or unsubstituted (C 3 -C 7) cycloalkyl, substituted or unsubstituted alkenyl, substituted alkynyl or unsubstituted, substituted or unsubstituted aralkyl, substituted or unsubstituted phenyl, and substituted or unsubstituted heteroaryl; z is 0 or 1 and when z is 1, A is CH, CR10 or N; D is N, CH, or CR12; E is H, OH, alkoxy or 2- (morpholino) ethoxy, C02H or C02alkyl; m = 0-2; r is 1 or 2, and wherein when r is 1, G is = 0 (oxygen with double bond) and when r is 2, each G is independently H, methyl, ethyl or propyl; R12 is selected from (CH2) kOH (where k = 1, 2 or 3), CH2NH2, CH2NH2-alkyl, CH2N (alkyl) 2, C02H, C02alkyl, C0NH2, OH, alkoxy, aryloxy, SH, S-alkyl, S -aryl, S02N (alkyl) 2 S02NHalkyl, S02NH2, S02alkyl, S03H, SCF3, CN, halogen, CF3, N02, NH2, 2 ° -amino, 3 ° -amino, NH2S02 and C0NH2, and wherein J is CR10 or N; R9, R10 and R11 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, (CH2) nOH (n = 2 to 3), CH2NH2, CH2NHalkyl, CH2N (alkyl) 2, halogen, CHO, CH = NOH , C02H, C02-alkyl, S-alkyl, S02-alkyl, S-aryl, S02 (alkyl) 2, S02NHalkyl, S02NH2, NH2, alkoxy, CF3, SCF3, N02, S03H and OH, including salts thereof where the microorganism is a selected member of Actinobacillus species, Porphyromonas species, Tannerella species Prevotella species, Eubacterium species, Treponema species, Bulleidia species, Mogibacterium species, Slackia species, Campylobacter species, Eikenella species, Peptostreptococcus species, Peptostreptococcus species, Capnocytophaga species, Fusobacterium species , species Porphyromonas and Bacteroides species. Method according to claim 13, characterized in that the microorganism is a member selected from Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythensis, Prevotella intermedia, Eubacterium nodatum, Treponema denticola, Bulleidia extructa, Mogibacterium timidum, Slackia exigua, Campylobacter rectus, Eikenella corrodens, Peptostreptococcus micros, Peptostreptococcus anaerobius, Capnocytophaga ochracea, Fusobacterium nucleatum, Porphyromonas asaccharolytica and Bacteroides forsythus. 15. Method according to claim 13, characterized in that the compound has the structure according to wherein m is 0. 16. Method according to claim 15, characterized in that E is OH, R9 is H and R * and R ** is each independently selected from substituted or unsubstituted phenyl. 17. Method according to claim 16, characterized in that R * and R ** are each independently selected from 4-alkyl, 3-halogen-phenyl and 4-halogen, 3-alkyl-phenyl. 18. Method according to claim 17, characterized in that R * and R ** are 4-methyl, 3-chlorophenyl. 19. Method for treating or preventing periodontal disease in a human or animal, characterized in that it comprises administering to the human or animal a therapeutically effective amount of a compound having a structure according to one of the following formulas: where B is boron, 0 is oxygen, R * and R ** each is independently selected (C 1 -C 4) substituted or unsubstituted alkyl, substituted or unsubstituted (C 3 -C 7) cycloalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aralkyl, substituted or unsubstituted phenyl, and substituted or unsubstituted heteroaryl; z is 0 or 1 and when z is 1, A is CH, CR10 or N; D is N, CH, or CR12; E is H, OH, alkoxy or 2- (morpholino) ethoxy, C02H or C02alkyl; m = 0-2; r is 1 or 2, and wherein when r is 1, G is = 0 (oxygen with double bond) and when r is 2, each G is independently H, methyl, ethyl or propyl; R12 is selected from (CH2) k0H (where k = 1, 2 or 3), CH2NH2, CH2NH2-alkyl, CH2N (alkyl) 2, C02H, C02alkyl, C0NH2, OH, alkoxy, aryloxy, SH, S-alkyl, S -aryl, S02N (alkyl) 2 S02NHalkyl, S02NH2, S02alkyl, S03H, SCF3, CN, halogen, CF3, N02, NH2, 2 ° -amino, 3 ° -amino, NH2S02 and C0NH2, and wherein J is CR10 or N; R9, R10 and R11 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, (CH2) n0H (n = 2 to 3), CH2NH2, CH2NHalkyl, CH2 (alkyl) 2, halogen, CHO, CH = N0H , C02H, C02-alkyl, S-alkyl, S02-alkyl, S-aryl, S02N (alkyl) 2, S02NHalkyl, S02NH2, NH2, alkoxy, CF3, SCF3, N02, S03H and OH, including salts thereof. 20. Method according to claim 19, characterized in that the compound has a structure according to wherein m is 0. 21. Method according to claim 20, characterized in that E is OH, R9 is H and R * and R ** is each independently selected from substituted or unsubstituted phenyl. 22. Method according to claim 21, characterized in that R * and R ** are each independently selected from 4-alkyl, 3-halogen-phenyl and 4-halogen, 3-alkyl-phenyl. 23. Method according to claim 22, characterized in that R * and R ** are 4-methyl, 3-chlorophenyl. 24. Method according to claim 19, characterized in that periodontal disease is a selected member of gingivitis, periodontitis and juvenile / acute periodontitis.