MXPA96004849A - Link of e-selectine, p-selectine or l-selectine with sialil-lewis (x) or sialil-lewis - Google Patents

Abstract

The invention relates to compounds having the general structure (II) which inhibits the binding of E-selectin and / or P-selectin on sialyl-Lewis (x) or sialyl-Lewis (a) present on a cell surface. This invention also relates to methods for inhibiting the binding of E-selectin and / or P-selectin on sialyl-Lewis (x) or sialyl-Lewis (a) present on a cell surface by the use of said compounds, and also to pharmaceutically active compositions comprising compounds that inhibit the binding of E-selectin on sialyl-Lewis (x). This invention also relates to methods for using said compounds for the treatment of septic shock, ARDS, Crohn's syndrome, chronic inflammatory disease such as, for example, psoriasis and rheumatoid arthritis, and reperfusion damage occurring after heart attacks, stroke and degen transplants

Description

LINK OF E-3ELECTIA, P-5ELECTIN OR L-SELECTIN WITH SJ.ALIL- E SSÍ?) OR SIALIL-LEWIS (a) CROSS REFERENCE WITH RELATED REQUESTS The present application is a request for continuation in 5 part of the American Salicitud with Serial Number 08 / 235,293, filed on April 29, 1994. TECHNICAL FIELD This invention relates to compounds that inhibit the binding of E-selec ina, P-selectin or L-sel 11 na with ialil-i Leu .1 s < . < y = ia 111 -Lam IS'H) and methods of in ibi in the linkage of? - -electin, P-sßlsctipa or L-selectina a -.alil- Le ii? f, '' or 5 L a] 11- Lei-j is fa) using said compounds. This invention also relates to pharmaceutically active compositions comprising compounds that 15 inhibit the binding of E-selectin, P-selectin or L-selectin with sia 1 i 1-Leuns (x) or sia 1 i 1-Leu? is í). . BACKGROUND OF THE INVENTION E-selectin also called ELAt-1 for the endatelial leukocyte adhesion molecule-1 and LECAM-2 for the lectin cell adhesion molecule 0, is a glycoprotein found on the surface of cells endothelial cells, the cells that form the lining of the inner wall of the capillaries. E-selectin recognizes and binds with carbahydrads sial i 1-Lewiß (x) (sLe (->), which is present on the surface of certain blood cells white E-selectin helps white blood cells recognize and adhere to the wall of capillary vessels in areas where the tissue surrounding the capillary vessel has been infected or damaged. E-selectin is one of the three select inas known to date. The other two selectins are L-selectin and P-selectin. P-selecfcin is expressed in inflamed endatelium and in platelets, and has a structure very similar to E-selectin and can also recognize if 1 i-Le.-.is (). L-selectin is expressed .0 in the leukocytes and also has a structure very similar to the P-sel ctina and the E-selec t i na. The structure of sia 1 i I-Leu. ís' x > and sial i: I-Lew is < a) (sLe (a)) are presented in formulas I (a) to I (b) below: Ne -.?e a - * - 3 Ca.01.3 GtcNAc - 5 I Fucal-4 Ib When a tissue has been invaded by a microorganism or damaged, white blood cells, also known as leukocytes, play a major role in the inflammatory response. One of the most important aspects of the inflammatory response involves the cell adhesion event. In general, white blood cells are circulating in the bloodstream. However, when a tissue is infected or damaged, the white blood cells must be able to recognize the invaded or damaged tissue and be able to attach to the wall of the capillary vessel near the affected tissue and spread in the capillary vessel in the affected tissue. E-selectin helps two particular types of white blood cells to recognize the affected sites and binds to the capillary wall so that these white blood cells can spread into the affected tissue. There are three main types of white blood cells: granulocytes, manacitos and lymphocytes. Among these categories, E-selectin recognizes sLe (x) presented as a glycoprotein or glycoprotein on the surface of manocytes and neutrophils. Neutrophils are a subclass of granulocytes that phagocytose and destroy small organisms, especially bacteria. The arthrocites, after leaving the bloodstream through the wall of a capillary, mature in macrophages that phagocytose and digest invading microorganisms, foreign bodies and senescent cells. The monocytes and neutrophils can recognize the site in which the tissue has been damaged by the binding are E-selectin, which is produced on the surface of the endothelial cells that constitute the lining of the capillary vessels when the tissue surrounding it. a capillary has been infected or. damaged. Typically, the production of E-5e 1ec 11 na =. and of P-selectins is increased when the tissue adjacent to a capillary vessel is affected. P-selectipa is present consti utively in storage granules from which it can be rapidly mobilized to the cell surface after activation of the endothelium. In contrast, E-selectin requires de novo ANP and protein synthesis, and peak expression is not observed until approximately 4-6 hours after activation, and decreases to baseline levels after approximately 24-48 hours. The white blood cells recognize the affected areas because the sLe (:.) Portions present on the surface of white blood cells bind to E-selectin and P-selectin. This binding decreases the flow of white blood cells through the bloodstream, since it mediates the movement of leukocytes along the activated endothelium before binding and migration mediated by the , and integpna, and helps locate white blood cells in areas of damage or infection. While the migration of white blood cells to the site of the wound helps fight infection and destroy foreign material, in many cases this migration can get out of control, with white blood cells flooding the scene, causing damage to your skin. broad. Compounds capable of blocking this process can, for the time being, be beneficial as therapeutic agents. For the first time, it would be useful to develop inhibitors that could prevent the binding of white blood cells to E-selectma or P-selectin. For example, some of the diseases that could be treated by inhibiting the selectin binding on sLe-¡< ) what 15 include, but are not limited to, APDS, Crohn's syndrome, septic shock, traumatic shock, organ failure > -. " Multiple autoimmune diseases, asthma, inflammation of the intestines, psoriasis, rheumatoid arthritis and reperfusion damage that occur during 20 heart attacks, strokes and organ transplants. In addition to being found in some white blood cells, sLe (a), a regulatory isomer that is closely related to sLe-x) is found in vain cancer cells, including cancer cells of the lung and colon. It has been suggested that this adhesion involving sLe (a) may be involved in the metastasis of certain cancers. COMPENDIUM OF THE INVENTION The present invention provides compounds having the structure of formula II which is presented below: II where X is selected within the group consisting of -CN, - (CH2) nC02H, -0 (CH2) mC02H, - < CH2) nC0Z, - (CH2) nZ, CHC02H < CH2) mC02H, - (CH2) n0 (CH2) mC02H, -CONH (CH2) mC02H, - CH (OZ) (C02H), CH (Z) (C02H), - < CH2) nS03H, - (CH2) nP03DlD2, - NH (CH2) mC02H, - CONH (CHP.?) C02H, (1-H-tet razol i l-5-a lqui 1-), and -OH; R1 and R2 are independently selected from the group consisting of hydrogen, alkyl, halogen, -OZ, -N02, - < CH2) nC02H, -NH2 and -NHZ; R3 is selected from the group consisting of hydrogen, alkyl, -OZ, -NHZ; R 4 is selected from the group consisting of hydrogen, halogen, alkyl, hydroxyl, hydroxyl sulfate-Q and -OZ; R5 is selected from the group consisting of hydroxy, -CN, -N3, -NH2, -NHNH2, -NE1E2, -NH31, -NHCO (CH2.NC02H, -S (CH2) MC02H and -NHCHNHNH2; > is selected from the group consisting of hydrogen, alkyl, aralkyl, hydroxyalkyl, aminoalkyl, alkylcarboxylic acid, and Ikto lboxamide, where n is 0 to 6, is 1 to 6, p is 0 a?, b is from 0 to 2, Z is alkyl, aryl or aralkyl, DI and D2 are independently hydrogen or alkyl, The is alkyl or -? CH2) aC02H where a is from 1 to 18, and E2 is alkyl, and pharmaceutically acceptable salts, esters, amides and prodrugs thereof. More particularly, this invention provides compounds where X is -Q, - < CH2) nQ, -0 (CH2) nQ, - < CH2) n0 (CH2) mQ, C0NH (CH2) nq, -NH (CH2) mQ, -0 (CH2) nO (CH2) mQ, or -CONH (CHRÓ..Q; R1 and R2 are independently selected from the group consisting of hydrogen and - (CH2.nQ; R4 is hydroxyl or hydrogen; R? Is selected from the group consisting of hydrogen, alkyl, aralkyl, hydroxyalkyl, aminoalkyl, alkylcarboxylate , ali le rba amid, Q is -C02H, n is from 0 to 6, and is 1 to 6 the pharmaceutically acceptable salts, steres, amides and prodrugs thereof. In a further embodiment, the present invention focuses YÓ towards compounds of formula IV: IV. - where W is hydrogen, alkyl or fa-D-mannosyl and Y is selected from H / H, oxygen, H / h idroxy, H / NH2, H / NHE1, H / NE1E2, NH, NEl, oxime and 0-alkyl lox, and the salts, IO pharmaceutically acceptable esters, amides and prodrugs thereof. The present invention also proposes a method for the inhibition of E-selectipa or P-selectin on sLe (x) or sLe (a) comprising the step of administering to a patient an amount of tissue of a compound having the structure of formula II, III or IV to inhibit the binding of E-selectin, P-selectipa or L-selectin on sLe (x) or sLe < a > , and a pharmaceutically active composition comprising a compound of formula II, III or IV and a pharmaceutically acceptable carrier. A method is also provided for the treatment of diseases such as ARDS, Crohn's syndrome, septic shock, traumatic shock, multiple organ failure, autoimmune diseases, asthma, disease * .0 inflammation of the intestines, psoriasis, arthritis, rheumatoid arthritis, reparfusion damage that occurs after heart attacks, apoplexy and organ transplants, which comprises administration to an animal that requires such treatment of a therapeutically effective amount of a 15 compound that has the formulas II, III or IV to reduce the symptoms of the disease. and._ DETAILED DESCRIPTION OF THE PREFERRED MODALITIES It has been found that compounds of formulas II, III and IV act to inhibit the binding of E-selectin, P-selectin or 20 L-selectin on sLe (x) or sLe (a). The compounds of the formula II comprise two main components: a portion derived from a mannopyranoside (a carbohydrate) and a biphenyl portion. In relation to the anopyranose portion, D-hand are preferred 25 compared to L-mannopyranosides, and the Absolute stereochemistry presented in formula II at positions C3 and C4 of sugar cane. However, an epimeric stereochemistry was allowed in the C2 position of the carbohydrate position (using glucopiums). The carbohydrate portion will be referred to herein as an anapyranoside for simplicity. Likewise, the alpha-ano is preferable in comparison with the a-anomer. The mannopyranoside portion binds to the biphenyl portion via a bridge -0-fCH2) b- where b is from 0 to 2. Preferably, the mannoside is attached at the ortho or meta positions on the phenyl ring. In addition, the anopharyoside moiety may be substituted.

Especially preferred are the missed handpieces having substituents at positions C2 and C6. For example, the mannose position 6 can be substituted with groups such as, for example, hydroxyl, -CN, -N3, -NH2, -NHNH2, -NE1E2, -NHE1, -NHC0fCH2) nC02H, -S (CH2) mC02H or - NHCHNHNH2 where n is from O to é > , is from 1 to 6, He is alkyl or - (CH2) 8C02H and E2 is alkyl. In the same way, the C2 position can be substituted with hydrogen, halogen, alkyl, hydroxyl, hydroxy-Q-sulfate or alkoxy. It is preferred, however, that the alkyl group is a lower alkyl group. It is also recognized that the hand portion may have , substituents in positions C2 or C6 or in both positions. The second component of the compound of the present invention comprises a diphenyle portion. The diphenyl portion can 5 is substituted in both phenyl groups or can be substituted only in a phenyl group. In addition, each phenyl group can have more than one member. The phenyl group that is not. directly fixed on the brown portion is replaced. Preferably, this Y-1-phenyl group is substituted at the 3-4-position or at least one of the groups consisting of -CH2) nCH3, -CN, - < CH2) nC02h, -0 (CH2) mC02h, (CH2) nü (CH2) mC02H, -fCH2) nC0Z, - < CCH2) nZ, -CHC02H (CH2) mC02H, -C0NH (CH2) mC02H, -CH1OZ) (C02H), -CH (Z) (C02H), - (CH2) nS03H, -15 (CH2) nP03DlD2, -NH (CH2) mC02H, -CONH (CHR?) C02H, UH- tetrazoi i 1-5-lq? 1-) and -OH dodne n is from 0 to 6, m is from 1 to --- 6, z is alkyl or aryl, DI and D2 are independently hydrogen or alkyl, P.6 is selected from the group consisting of hydrogen, alkyl, aralkyl, hydroxyalkyl, 20 to inova l, icarboxylic acid and alkylcarboxamide. If the fenium group not directly fixed on the mannopyranoside portion is substituted with more than one substituent, then a substituent is at the 3 or 4 position and is preferably selected within the 25 group consisting of - < CH2) nCH3, -CN, - (CH2) nC02h, / ", 0-CH2) mC02h, - (CH2) nO (CH2) mC02H, - (CH2) nC0Z, - < CCH2) nZ, - CHC02H (CH2) mCQ2H, -CONH < CH2) mC02H, -CH (QZ) IC02H), CH (Z) (C02H), - < CH2) nS03H, - (CH2) nP03D! D2, -NH (CH2) mC02H, - C0NH (CHR6) C02H and (1-H-tetrazole i 1-5- lq i 1-) where n is from to 5 6, m is 6, Z is alkyl or aryl, R > it is selected from the group consisting of hydrogen, alkyl, aralkyl, hydroxyalkyl, amine-free, alkyl-1-carboxylic acid and q-icarbaxamid, and DI and D2 are independently hydrogen or alkyl. Any other JO substituent is selected. independently of the group consisting of hydrogen, halogen, alkyl, N02, C02H and OH. It may also be desirable to have substitution in the fepilo ring directly fixed on the portion of 15 m nopir ósido. Substituents are preferably selected from the group consisting of hydrogen, halogen, /, alkyl, alkoxy and alkylamine. The most preferred compounds of the present invention have the formula III. As used herein, the term "alkyl" refers to a monovalent group of income chain or branched chain 1 to 12 carbon atoms including methyl, ethyl, n-prapil, isopropyl, n-butyl, sec-butyl, isobutyl , tert-butyl and simlares, but not limited to them.

"The term" lower alkyl "refers to any alkyl group having 1 to 6 carbon atoms. The term "halogen" refers to any atom selected from the group consisting of chlorine, fluorine, 5-bromine iodine. The term "alkoxy" will refer to an alkyl group linked to a molecule by means of an oxygen atom, including methoxy, eta i, isopropoxy, n-butaxy, sec-butoxy, isobutoxy, tert-butaxy and the like, but without limitation. kiss them. .- The term "alkylamino" will refer, to groups that have the structure -NH- (to the one), or -N- (lqui lo), including, for example, melamino, ethylamino, isoprop i lam not and simi l res. The term "aryl" will refer to substituted or unsubstituted carbocyclic aromatic groups including phenyl, biphenyl 1 or 2-naphthyl, fluorenyl, (1,2) - dihydronaphtolyl, indenyl, indanyl, thienyl and the like, but without limit yourself to them. Substituents include other aryl groups or other groups thereof such as alkyl, alkoxy, alkylcarboxylic acid or manno groups. The term "aralkyl" (also referred to as arylalkyl) will refer to a substituted or unsubstituted aryl group added to an alkyl group including benzyl, 1 and 2-naphthylmethyl, halobenzyl, alkoxybenzyl, hydroxybenzyl, aminobenzyl, no robenci lo, guanidionobenci lo, f luorenilmetilo, - feni 1 and i (benzyl), 1-phenolyl, 2-phenolyl, 1-naphthylethyl and the like, but not limited thereto. The term "hydroxyalkyl" will refer to -OH added to an alkyl group. The term "aminoalkyl" will refer to a group having the structure -NRxRy added to an alkyl group. The groups P: - and Ry are independently selected from, for example, hydrogen, alkyl and aplo. The term "-alkylcarboxylic acid" will refer to a group r ~ * calboxyla-C02H) added to an alkyl group. The term "a lk Icarboxa ida" will refer to a group having the formula -CONR. ^ Py added to an alkyl group where Rx and Ry are co-defined above under the concept of inoal quilo. 5 The term "pharmaceutically acceptable salts, esters, amides, and prodrugs" in accordance with that used / ___ here refers to carboxylate salts, amino acid addition salts, esters, amides and prodrugs of the compounds of the present invention which are, within the scope of sound medical judgment, suitable for use in contact with witnesses of patients without excessive toxicity, irritation, allergic response and the like, co-ensured with a reasonable weight / benefit ratio, and effective for their intended use, as well as the 5-ionic forms, if possible, of the compounds of the , invention. The term "salts" refers to the relatively non-toxic organic and inorganic acid addition salts of the compounds of the present invention. These salts may be separated in situ during the isolation and final purification of the compounds or by the separate reaction of the purified compound in its free base form with a suitable organic or inorganic acid and by the isolation of the salt formed in this manner. Representative salts include salts of hydrobromide, hydrochloride, sulfate, bisulfate, nitrate, acetate, oxalate, Tolerates, oleate, pal itate, stear, laurate, borate, benzoate, lactate, phosphate, tosylate, c? treatment, maleate, fumarate, succinate, tartrate, naphthylate, mesylate, glucoheptonate, lac lobate, laup lulose and the like. They can include cations based on the alkaline earth metals and alkali, such as sodium, lithium, potassium, etc. calcium, magnesium and the like so as non-toxic ammonium, quaternary ammonium and amine cations including, ammonium, tetramet and ammonium, tetraet and ammonium, ethylamine, dimethylamine, methylmethane, triet and lamina, ethyl ina, and the like, without being limited to these. (See, for example, SM Berge, et al., "Pharmaceutical Salts," J. Pharm. Sci., O-o: 1-19 (1977), which is incorporated herein by reference.) Examples of non-toxic steres pharmaceutically acceptable compounds of this invention include . • ---. alkyl esters Cl to Co wherein the alkyl group is a straight or branched chain. Acceptable esters also include esters of C5 to C7 cycloalkyl as well as arylalkyl esters such as for example benzyl, without being limited thereto.

Preferred are C1 to C4 alkyl esters. Esters of the compounds of the present invention can be prepared according to conventional methods. Examples of non-toxic, pharmaceutically acceptable amides of compounds of this invention include amides derived from r .. or ammonia, C1-C to C-primary amides, and dialkyl-C1-C amides, where the alkyl groups are straight or branched chains. In the case of secondary amines, the amine can also be a heterocycle of • 5 or or members containing a nitrogen atom. The 5 amides derived from ammonia, primary C1 to C3 alkyl amides and dialkyl secondary amides Cl to C2 are And- prefire. Amides of the compounds of the present invention can be prepared according to conventional methods. The term "prafármaca" refers to compounds that are rapidly transformed in vivo to provide the starting compound of the above formula, for example, by hydrolysis in blood. IN "Pro-drugs as Novel Delivery Systems", by T. Higuchi and V. Stelia, Val. 14 of the A. C.S. Sympoxium Series, and in Bioreversible Carriers in Drug 5 Design, ed. Ed ard B. Roche, American Pharmaceutical Assaciatian and Pergamon Press, 1987, a full discussion of this topic is provided. Both jobs are incorporated herein by reference. The present invention also relates to pharmaceutically active compositions containing the compounds of the present invention. It is contemplated that the pharmaceutically active compositions may contain a compound of the present invention other compounds that inhibit or compete, with the binding of Es lect ina, P-seleeti na or L-sel c ina with 0 sl.e í) or sLe (a., including sLe > ') and sLe (p-) m smas- L active pharmaceutical compositions of the present invention comprise a fi rm vehicle. íol ó > j i co _. a compound of formulas II, III or IV. The pharmaceutical compositions of the present invention can include one or more of the compounds of the formulas II, III or IV formulated together with one or vain "Non-tacitly acceptable vehicles, auxiliaries or vehicles, collectively referred to herein as vehicles, for parenteral injection, for oral administration in solid or liquid form for rectal or topical administration and the like. The compositions can be administered to humans and animals either orally, rectally, parenterally, intravenously, intramuscularly or subcutaneously), in intracranial form 1, intravaginally 1, intraperitone 1, locally ^, (powders, ointments or drops), or in the form of buccal or nasal spray. Compositions suitable for parenteral injection may comprise sterile aqueous or non-aqueous physiologically acceptable solutions, dispersions, suspensions or emulsions and sterile powders for reconstitution into sterile injectable solutions or dispersions. Examples of suitable carriers, diluents, solvents or aqueous and aqueous vehicles include water, ethanol, polyol, -. (propylene glycol, polyethylene glycol, glycerol, and the like), suitable mixtures thereof, vegetable oils, such as, for example, olive oil, and injectable organic esters with, for example, ethyl oleate. Proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by maintaining the required particle size in the case of dispersions and by the use of surfactants. These compositions may also contain auxiliaries such as preservatives, wetting agents, emulsifiers, and dispersing agents. The prevention of the action of microorganisms can be assured by various antibacterial and anti-fungal agents, for example, parabens, chlorobutanal, phenol, sorbic acid and the like. It may also be desired to include isotonic agents, for example, sugars, sodium chloride and the like. The absorption The prolonged administration of the injectable pharmaceutical form can be obtained by the use of delayed absorption agents, for example, aluminum and gelatin. If desired, and for a much more effective distribution, the compounds can be incorporated into focused or slow-release or delayed delivery systems such as, for example, polymers, liposomes, and iesphere. They can be sterilized, for example, by filtering through a bacteria retention filter, or / ** i 'by the incorporation of sterilization agents in form IU. sterile, or any other sterile, sterile medium immediately before use. Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. In 5 such solid dosage forms, the active compound or a prodrug ester is mixed with at least one Y- usual inert excipient - or vehicle) such as for example sodium or dialytic acid phosphate or (a '< fillers or diluents, such as starches, lactose, sucrose, glucose, ol and acid silicic, < b) binders, such as, for example, carbamate, cellulose, alginates, gelatin, polypropylene, sucrose, and acacia, (c) humectants, such as, for example, glycerol < d) integration agent, for example, agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain Composite silicates and sodium carbonate (e) solution retarders, for example paraffin (f) absorption accelerators, such as, for example, quaternary ammonium compounds, (g) wetting agents, such as, for example, cetyl alcohol and glycerol mannostearate, (h) adsorbents, such as, for example, kaolin and bentonite and (i) lubricants, for example talc, calcium stearate, magnesium stearate, solid polyols, sodium lauryl sulfate or well mixtures of them. In the case i-i.i of capsules, tablets and pills, the form of doping can also comprise regulating agents. Solid compositions of a similar type can also be used as soft and hard gelatin capsule fillings using such excipients such as lactose or sugar. 15 milk as well as pal iet i. high molecular weight and imi lares. Y- Solid dosage forms such as for example tablets, dragees, capsules, pills and granules can be prepared with coatings and shells, such as for example enteric reversals and others well known in the art. They may contain opacifying agents, and may also be compositions that release the active compound or the active compounds in a certain part of the intestinal tract in a delayed manner. Examples of compositions of fm. coating that can be used polymeric substances and waxes. The active compounds can also be present in microencapsulated form, optionally, with one or more of the excipients mentioned above. Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms 0- may contain inert diluents commonly employed in the art such as for example water and other solvents, solution agents and emulsifiers, such as ethyl alcohol, isopropyl alcohol 1, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, 5-propylene glycol, 1, 3-butyl glycol, d imet i 1-id, oils, specifically cottonseed oil, oil Y- of peanuts, corn germ oil, olive oil, castor oil and sesame seed oil, glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and esters of sorbitan fatty acids or mixtures of these substances and the like . In addition to such inert digests, the compositions may also include auxiliaries, such as, for example, wetting agents, emulsifying and suspending agents, sweeteners, flavors and perfume agents.

The suspensions, in addition to the active compounds, may contain suspending agents, such as, for example, isotropic alcohols, ethoxylated, polyoxyethylene, and sorbitan steres, icrocrystalline cellulose, aluminum etahydroxide, bentonite, agar. agar and tragacanth or mixtures of these substances and the like. Compositions for rectal administrations are preferably suppositories which can be prepared by mixing the compounds of the present invention with suitable non-irritating excipients or vehicles such as cocoa butter, polyalkylene glycol, or a suppository wax which are solid. at oridinary temperatures but liquid at body temperature and therefore melt in the rectal or vaginal quality and release the active compound. Dosage forms for topical administration of a - < - compounds of this invention include ointments, powders, sprays and inhalations. The active component is mixed under sterile conditions with a physiologically acceptable carrier and any required amount of necessary preservatives, regulators or propellants. Ophthalmic formulations, eye ointments, powders and solutions are also contemplated within the scope of this invention.

-. The compounds of this invention can also be administered in the form of lipossmas. As is known in the art, the 1 ipaso s are generally derived from phospholipids or other lipid substances. The liposomes are formed of monohydrated or lamellar hydrated lipid crystals dispersed in an aqueous medium. Any metabolizable, physiologically acceptable, non-toxic lipid capable of forming 1 iposomes can be used. The present compositions in the liposome form may contain, in addition to the selectin binding inhibitors lu of the present invention, stabilizers, preservatives, excipients and the like. The preferred lipids are the phospholipids and the natural or synthetic phosph id i cholines (reagents). Methods to form 1 iposomes are well known in the 15 technique. The actual dosage levels of the active ingredient in * ~~ the compositions of the present invention can be varied to obtain an effective amount of active ingredient to obtain the desired therapeutic response for a particular composition and specific administration method. The selected dosage levels depend, therefore, on the desired therapeutic effect, on the route of administration, on the desired duration of treatment and on other factors. ., = ---_ The total daily dosage of the compounds of this invention administered to a host in single or divided doses may be within the range of approximately 5 mg to approximately 250 mg per kilogram. 5 of body weight. Dosage unit compositions may contain submultiples of the same used to form the daily dosage. It will be understood, however, that the level of days? specific ions for a specific patient, be it human or another animal, / r 0 will depend on several factors including body weight, general health, sex, diet, time and day of administration, rate of absorption and expression, combination with other drugs as well as the severity of the specific disease that is being treated. trying. In particular, the compounds of the present invention can be used to treat various diseases / I - related to inflammation and cell-cell recognition and adhesion. For example, the compounds of the present invention can be administered to a patient 0 to treat shock, chronic inflammatory diseases such as psoriasis and rheumatoid arthritis, and tissue damage by reperfusion that occurs after heart attacks, apaplegia and organ transplants. , traumatic shock, multiple organ failure, autoimmune diseases, asthma and intestinal disease t: _ inflammatory. In all cases, an effective amount of the compounds of the present invention is administered either alone or as part of a pharmaceutically active composition to a patient in need of such treatment. It is also recognized that a composition of the compounds can be administered to a patient who requires such administration. The compounds of the present invention can also be administered to treat other diseases associated with cell-cell adhesion. Since the 0 present compounds inhibit the binding of E-selectin, P-selsctipa or L-selectin with sl_e (x) or sLe (a), any disease related to this interaction can potentially be treated by inhibiting this interaction of link. 5 In addition to being found in some white cells, sLe (a) is found in several cancer cells, including cells , - of lung and colon cancer. It has been suggested that cell adhesion that involves sLe (a) may be involved in the stasis of certain cancers and that inhibitors of the 0 bond with sLe (a) may be useful for the treatment of certain forms of cancers. The compounds of the present invention can be synthesized in accordance with the general synthetic scheme presented in the scheme 1: 5 Scheme 1 twenty s - 0 where R is selected from the group consisting of - (CH2) nC02H, -0 -CH2) mC02H, - ÍCH2) O (CH2) mC02H, C0NH (CH2) mC02H, - CH (OZ) (C02H), -CH (Z) (C02H), - (CH2) nS03H, - (CH2) pP03Dl2, -NH (CH2 ') mC02H, -CONH (CHP.Ó) C02H, and (1 H-5 tet zol i 1.-5 - lqui 1-); where n is from 0 to 0, m is from 1 to 6, Z is alkyl, DI and D2 are independently hydrogen or r-alkyl, and R6 is selected from the group consisting of hydrogen, alkyl aralkyl, hydroxyalkyl, amipal , alkyiicarboxylic acid alkylcarboxamide, and the pharmaceutically acceptable salts, esters, and pharmacologically acceptable amides thereof. In this scheme, the desired di-pheni portion is synthesized and subsequently reacted with the desired mannosyl portion to form a compound of the present invention. 5 Specific examples of the synthesis of the compounds of the invention are presented in the experimental section below where R is as defined above. Other compounds can be synthesized in accordance with the schemes presented below where R is as defined above. Scheme 2 In this reaction scheme, a phenyl acetic ester is bonded with an aplboronic acid in the presence of a palladium and base catalyst to provide a compound / -. biphenyl. The phenol functionality reacts with a protected pharyasaid map in the presence of boron trifluoride etherate. The desired compound is obtained by the base treatment to hydrolyze the esters. Scheme 3 A substituted bromophenol reacts first with butyl lithium, then with trimetaxibarata followed by acid hydrolysis C to provide a boronic acid. This compound reacts with a substituted benzene benzene in a palladium (0) catalyzed bond to provide a diphenyl compound. The diphenyl compound is bound with a protected mRNA and the product is deprotected by basic hydrolysis to form the desired compound.

A bromobenzyl bromide is treated with sodium cyanide in 5 methanol at reflux to provide a bromobepci Ini tri lo.

This compound binds to a baronic acid in the presence of a palladium catalyst a base to provide a substituted biphenyl compound. The nitrile functionality is converted to a tetrasol by treatment with sodium azide and aluminum chloride in toluene under reflux condition. The tetrasol of bifepyl binds to a protected mannose derivative catalyzed by boron trifluoride etherate. The base treatment removes the protection of the material and provides the desired compound. Scheme 5 A bromophenyl acetate is treated with lithium diisopropylamide and an alkyl halide to provide an alkylaldehyde acetate. This compound binds with a boronic acid to produce a biphenyl compound. The biphenyl compound binds with a protected mannopi-daeaside using boron trichloroetherate and the compound is deprotected by basic hydrolysis to give the desired compound.

?OR Scheme or The scheme presents a general synthetic route to compounds that have several amide functional groups. First, a phenolic boronic acid reacts with a brsmobenzoic acid to obtain a diphenyl using potassium phosphate and a catalytic amount of baladium (O) tetrakistri pheny1 phosphine in dimethyl formamide and water. Then, the diphenyl portion that is attached is then esterified with mannose pentaacetate. The acetate protection groups are then converted to acetonide protection groups using sodium methoxide in ethans followed by acetone and di-etaxypropane with a catalytic amount of p-taluenesulfonic acid. The basic hydrolysis of the ester provides an acid which can be converted to several amide groups by reaction of the acid with a particular amino ester, in the presence of standard coupling reagents. Then, the compound is stripped to provide the desired amide. Scheme 7 Reagents and conditions: a) LiBH4, THF taluene b) MsCl, Et3N c) potassium thioacetate d) Oxone, H20 / MeOH e) dess-martin periodipana, CH2C12 f) CH (P03Et2) 2, THF g) H2, Pd / C, MeOH h) H +, H20 i) NaOH, H20, delta . "" "A compound having a diphenyl portion and a portion of capped manapiranoside protected with acetates synthesized according to the scheme or above may react with lithium borahydride in tetrahydrofuran and toluene to produce a compound having an alcohol group. Phenylethyl on the diphenyl portion This can react with mesyl chloride and triethylamine followed by potassium thioacetate to provide an alkyl thiaacetate, this thioacetate can be treated additionally \ 'j with oxono in water and methanol. to provide a diphenyl compound substituted with suphthalic acid. Ally, alcohol, phenylethyl can be treated with the Dess-Martin reagent to provide an aldehyde which can then be treated with tetraethylene diphosphonate anion 15 to produce an alpha, beta-unsaturated phosphonate. The reduction with hydrogen and a palladium catalyst produces Y- the corresponding diethylphosphonate, which may then be partially hydrated with an aqueous base to provide an ethyl phosphonic acid. 0 Scheme 8 5 A compound substituted with a mannitol protected from conformity with that prepared in Scheme 2 is first treated with sodium methoxide in methanol, then dimethoxyphosphide in acetone with catalytic acid to give a 0-bisacetomide. Partial deprotection by mild acid hydrolysis, followed by reaction of the primary o-hydroxyl group with tasly chloride gives an acetylated hydroxy tosylate with acetic anhydride in pyridine. The tosylate group is replaced with iodine using sodium iodide in 5-dimethyl formamide. The treatment of iodide with azide Sodium in DMF provides an azido compound either deprotected to provide the o-azido compound, or reduced in an amine after reversion of the acetate protection group. Further removal of the remaining protection groups by treatment with catalytic acid in methanol followed by hydrolysis provides the desired o-amino compound, This scheme shows that the o-iodomanopyroside in accordance with that synthesized in scheme 8 can be displaced with a sulfur-based nucleophile to generate the o-mercapto-S-acetate ester, which can subsequently be deprotected by mild acid hydrolysis and then basic hydrolysis sequentially to provide the white compound. Scheme 10 In this scheme, a bromophenyl acetic acid. The substituted one is combined with a boronic acid substituted hydroxyl imeti lbencen using a palladium (0) catalyst, and the product is esterified. The resulting ester is glycosylated with a protected mannospyranoside in the presence of boron troflouride etherate. Hydrolysis of the protecting groups provides the desired compound. Scheme 11 A substituted bromophenol reacts with ethyl bromoacetate in the presence of sodium hydride to provide a substituted bromophenyl ether attached to a hydroxybenzeneboronic acid using catalytic palladium (0) to provide a substituted difpiphenyl. The phenol reacts with a protected mannose unit using boron trifluoride etherate to provide a protected mannitoloside. The treatment with an aqueous base provides the compound In this scheme, a substituted bromophenol reacts with ethyl bramoacetate in the presence of a suitable base to give a bramofenyl ether. The halide then reacts with a boronic acid in the presence of catalytic palladium (O) to produce a substituted diphenyl compound bound with a protected mannose unit in the presence of etherate boron trifluoride. The protecting groups are then removed with aqueous hydroxide which produces the desired compound. Scheme 13 In this reaction scheme, a bro-cinzyme bromide reacts with sodium cyanide in methanol to give a cyana et ibrabrabenzene. The halide then reacts with a boropic acid in the presence of a palladium (0) of catalytic tetrakistrifenphosphine to produce a substituted diphenyl compound coupled with a mannose unit protected in the presence of boron trifluoride etherate. The protecting groups are then stirred with aqueous hydroxide which produces the desired compound. Scheme 14 a ??? Ac) s BF ^ O -8 A substituted 2,2'-dihydroxylurea is reacted with ethyl bromine acetate in the presence of sodium hydroxide to give a phenol diphenyl ether. Phenol reacts with a hand. protected monostearate using boron trifluoride etherate, and the protecting groups are then stirred with an aqueous base to give the desired compound. Scheme 15 This scheme illustrates that a substituted bromophenol can be converted to a substituted benzene boronic acid by < -. treatment with a suitable base followed by the introduction of trimethyl borate and then hydrolysis. The resulting boronic acid is then attached with a bra ether ether in the presence of palladium (O) catalyst to give a substituted diphenyl phenol. The phenol reacts with a protected manure unit in the presence of boron trifluoride etherate, and the protecting groups are then removed with aqueous base to give the desired product. m Scheme l This scheme shows that a bromophenyl ether in accordance with that prepared in scheme 2 can react with a 3-hydro? lboronic imetifeni in the presence of palladium (0) to give a substituted diphenyl compound. The hydroxy group reacts with a unit of protected by using boron trifluoride co-adjuvant etherate. The treatment with an aqueous base provides A substituted 3-bromafepol reacts with ethyl bramoacetate in the presence of sodium hydride to provide the substituted bromophenyl ether attached with a 3-hydra imeti-benzeneboronic acid using a catalytic palladium () to provide a substituted biphenyl compound. The benzyl alcohol reacts with a protected mannose unit using boron trifluoride etherate to give a protected mannoside. The treatment with an aqueous base then provides the desired compound. Scheme 18 In this scheme, a 4-bromof nol. The substituted one is reacted with ethyl bromadiacetate in the presence of sodium hydride to give a bromophenyl ether. The halide is attached with 3-hydrox imeti lbencen boricone using catalytic palladium (0) to give a substituted biphenyl compound. A portion of protected mannose is introduced and the resulting glycoside is treated with an aqueous base to provide the desired compound. Scheme 19 In this scheme, a bromobenzoic acid is bound to a 3-hydrox imet i 1 fep 1 boronic acid using palladium (0) co or r + -catalyst. Reaction with a protected manure unit, followed by removal of the protection induced by a base provides the desired compound. Scheme 20 In this scheme, methyl acetate 1-3- (2-methoephex 1) phene in accordance with that prepared in part B of example 1 reacts with a bro-ofenyl acetic acid chloride using aluminum chloride in a suitable solvent to give a substituted acetophenone. The reaction with an aryl boronic acid in the presence of palladium < 0 > Catalytic and aqueous sodium carbonate in toluene provides a substituted tetra-aryl compound. Treatment with boron tribromide in a halogenated solvent at a low temperature gives a phenol that reacts with a hand protected by using boron trifluoride etherate. Treatment with an aqueous base provides the desired compound.

In this scheme, a tetra-aryl compound according to that synthesized in scheme 20 is treated with an aqueous base to convert the ester functionality to a carboxylated salt, which is then treated with hydrazine and potassium tert-butoxide followed by acidification to give a disubstituted ethane portion. The ether groups are removed using boron tribromide in a halogenated solvent, and the carbaxylate is esterified again to give a di-phenol ether. The reaction of the phenols with a protected unit of iodine followed by base-induced deprotection provides the desired compound. Scheme 22 In this scheme, a phenylsuccinic acid is esterified using an alcohol in the presence of catalytic acid to give a phenyl diester which is then treated with vapors of nitric acid and sulfuric acid to provide a diester or rhephenyl. The nitro group is reduced using Raney nickel and hydrazine, or other suitable reduction conditions known to those skilled in the art, and the resulting amino group reacts with acetic anhydride to provide an acetamide. The introduction of the halogen is achieved using bromine in a suitable solvent and the acetamide is then hydrolyzed using an aqueous acid. The resulting amino group is removed by treatment with nitrous acid followed by Acid h ipofosfaroso. The aryl halide then reacts with a hydroxyphenyl boronic acid in the presence of catalytic palladium (O) to give biphenyl phenol which then reacts with a protected mannose unit. The aqueous-based treatment removes the protecting groups and provides the desired compound. Scheme 23 0 4 A phenyl diacetic acid is treated with alcohol in the presence of catalytic acid to give a diester. The aromatic ring is subsequently treated neither using vapors of nitric acid and sulfuric acid to give a nitraphenyl diester, and the nitro group is reduced using Raney nickel and hydrazine, or other suitable reduction conditions known to those skilled in the art. matter. The resulting amino group then reacts with acetic anhydride to give an acetamide. Halogen is introduced using bromine in a suitable solvent, and the acetamide is then hydrolyzed using acidic acid introduced using bromine in a suitable solvent, and the resulting amino group is removed by treatment with nitrous acid followed by hypophosphalous acid, and the aryl halide then reacts with hydroxyphenyl boronic acid in the presence of catalytic palladium (0) to give a diphenyl phenol. The treatment with a protected mannose unit and boron trifluoride etherate affords ana-ananoside which is then treated with an aqueous base to provide the desired compound. Scheme 24 A nitrophenyl acetic acid is first converted to an ester using an alcohol and catalytic acid, then the aromatic ring is halogenated using bromine and iron in a suitable solvent. The nitro group is then reduced using hydrazine and Raney nickel. The resulting amino group is diazotized using sodium nitrite in aqueous sulfuric acid, and the diazonium salt hydrolyzed in the phenol with aqueous acid. Phenol is protected using acetic anhydride and the alura The aromatic is then reacted with a hydroxyphenyl boronic acid in the presence of catalytic palladium (0) to provide a biphenyl phenol. Treatment with a protected mannose portion followed by removal of the base-induced protection gives the desired acetic anhydride compound to provide an acetamide. Halogen is Scheme 25 This scheme shows that bromofepsl according to that prepared in scheme 24 can be alkylated using an aryl halide or alkyl and a suitable base. The reaction of the resulting aryl haloether with a hydroxyphenyl boronic acid using palladium (0) co or catalyst provides a biphenyl phenol which is then reacted with a protected mannose unit. Treatment with an aqueous base provides the desired compound. Scheme 2 A 3-alk acid The lactic acid is treated with an alcohol in the presence of catalytic acid to provide an ester, which is subsequently nitrated using vapors of nitric acid and sulfuric acid. The nitro group is reduced using methods known to those skilled in the art, and the resulting amino group is acetylated using acetic anhydride. Treatment with bromine in a suitable solvent followed by hydrolysis of acetamide provides a bromsanite. The amino group is removed by means of a diazotization sequence followed by reduction of the diazonium salt with hypophosphorous acid. The aromatic halide binds with a hydraxy phenyl-boronic acid in the presence of catalytic palladium () to give a diphenylene phenol, which binds with mannose pentaacetate. The compound is desprateje "-. then with an aqueous base to provide the desired compound. The following examples further illustrate the invention and are not intended to limit the specification or the rei indications. EXAMPLES EXAMPLE 1 ACID 3- (2- (ALPHA-D-MAN0PIRAN0SIL0XI) PHENYL) FEN.ILACETIC0 Part A: Was 3-bromophen acid dissolved? lacetico (2.0 g, 9.3 mmol in methanol (20 ml) in a 50 ml flask, concentrated sulfuric acid (2 drops) was added and the mixture was refluxed under nitrogen for 10 hours and then concentrated under reduced pressure. The residue was mixed with dichloromethane (20 ml) and a saturated sodium bicarbonate solution (10 ml), the organic material was separated, dried (MgSO 4) and concentrated - / - "reduced pressure." The residue was rinsed through a silica gel with hexane-ethyl acetate (3: 1), and concentrated to provide 2.12 g (99 * /.) Of (3-bromopheni-1) -acetate. methyl, which was used without any further purification, Part B: Aniso! 2.1 g, 20.0 mmol) was dissolved in dry THF (50 ml) in a dry 100 ml flask rinsed with nitrogen. dry ice bath / 2-prapanol, n-butyllithium (10.9 ml of a 2.3 M solution in Hexans, 25 mmol), after the cooling bath was changed to a bath of ice water. The reaction was stirred for 1 hour at 0 degrees C, then trimethyl borate (2.3 ml, 20 mmol) was added and the mixture was stirred at room temperature overnight. The reaction mixture was treated with 2N aqueous HCl to a pH of 3 and mixed well for 30 minutes, then extracted with ether (3 x 15 ml). The organic materials were combined, dried (MgSO4 >; , then concentrated under reduced pressure which provided 2.88 g (957.) of 2-meta ibenceporboronic acid in the form of a clear oil which was used in the next step without any further purification. < 3-bromophene 1) methyl acetate (2.0 g, 9.0 mmol), tetrakis (tri-phenyl-1-phosphine) palladium (0) (115 m), sodium carbonate (2. g, 25 m in 2 ml of water) and toluene (10 ml) were degassed under a nitrogen atmosphere in a 25 ml flask equipped with a reflux condenser. 2-Methoxybenzeneboronic acid (1.5 g, 9.87 mmol) in toluene (1 ml) was added and the mixture was heated under reflux condition overnight, then mixed with sodium chloride / ethyl acetate (15 ml) saturated 1: 1. The organic materials were separated, dried (MgSO 4), and then concentrated under reduced pressure which afforded 2.81 g of methyl (3- (2-methoxy phenyl) pheny1) acetate.

, -. Part C: In a 250 ml dry flask, 3- (2-r * metho-ifeni 1) feni 1) phenylacetate methyl (2.0 g, 7.8 mmol) was dissolved in diclaromathane (100 ml) under nitrogen atmosphere, and cooled in a dry ice / 2-propanol bath. Boron boron (2.2 ml, 24 mmol) was added slowly, dropwise and the mixture was kept at a temperature of -10 degrees C for 14 hours, then mixed with ice water (100 l). The organic material was separated, washed with a saturated sodium bicarbonate solution (50 ml), water (50 ml), / - saturated sodium chloride (0 ml), then dried (MgSO 4> and concentrated under reductive pressure.) The residue was purified by flash chromatography (SiO 2, 3: 1 hexane / ethyl acetate) to give 1.25 g (0.25 g). (3-bramafepine) methyl acetate) 3- (2-h-idraxypheny1) phenylacetate methyl ester in the form of a clear oil Part D: 3- (2-Hydrylsulfonic acid) * -methyllacetate (1.28 g, 5.28 mmol) in 1,2-dicylschromethane (20 ml) in a 50 ml dry flask, Alpha-D-mannose pentaacetate (2.08 g, 5.34 m al) was added in one part, then boron trichloride etherate (2.32 ml, 18.5 mm) was added slowly, the mixture was applied under a nitrogen atmosphere overnight at room temperature, then mixed with water (50 ml), the organic material was separated and the aqueous part was extaida with dichlorametapo (3 x 5 ml), The extracts were combined with the fraction organic, dried (MgSO4), and then concentrated under reduced pressure. The residue was purified by flash chromatography (Si02, elution gradient of hexane to 3: 1 hexane / ethyl acetate) which yielded 2.74 g (9> g) of 3- (2 < 2,3,4,6 -tetra-Q-acetylfa-D-anopyranosi loxi) feni 1) phenylacetate methyl ester contaminated with a small amount of unreacted alpha-D-mannose pentaacose that was caulked with the product. 3- (2- (2,3,, o-tetra- -aceti-1-alpha-D-manop i ranosi lo? I) feni 1) phenylacetamide of methyl (2.74 g, 4.78 mmol) was dissolved in acetonitrile (25). ml) in a 50 ml flask and treated with a solution of lithium hydroxyl monohydrate (1.1 g, 0.2 mm) in water (10 ml) and the mixture was stirred at room temperature overnight and then acidified to room temperature. a pH of 2 with concentrated hydrochloric acid The mixture was concentrated under reduced pressure and the residue was ,, - purified by HPLC (reverse phase), gradient elution 5-50 *? of acetonitrile in water (trieroacetic acid 0.1 '/'), monitored at 154 nm) which yielded 0.87 g (47 * S) of 3- (2- (alf-D-manop i ranosi la i) feni 1 ) lactic pheni in the form of a white solid with a melting point between 85 and 8 degrees C. 1 H NMR: (300 MHz, DMSO-do) 7.02-7.40 (comp, 8H), 5.31 (s, lH), 3.25 -4.00 (comp, 12H) ppm.

IR (KBr): 3408, 1791, 1713, 1478, 1223, 1171, 1019, 979, 755 cm-1. Analysis: Cale for C20H2208_1.5 (H20): 57.55% C, 5.7% H. Found: 57.33% C, 5.59% H. EXAMPLE 2 ACID 4- (2- (ALPHA-MAN0PIRAN0SIL0XI) PHENYL) PHENYLACETICUM Part A: Operation in the same manner as in part A of EXAMPLE 1, but the use of 4-bramofeni lactic acid provided methyl 4-bromophenilacetata in a yield of 85% r. Part B: 2-Bromophene (10.0 g, 57.8 mmol) was dissolved in dry THF (100 mL) in a 250 mL dry flask rinsed with nitrogen. The mixture was cooled in a dry ice / 2-propapal bath, n-butyllithium (51 ml of a 2.5 M solution in hexanes, 127.2 mmol) was added, then the cooling bath was changed to an ice water bath . The ? The reaction was stirred for 1 hour at 0 degrees C, then trimethyl borate (0.1 ml, 0.7 mmol) was added to the paste which became homogeneous after a few minutes. The mixture was stirred at room temperature overnight, then treated with 2N aqueous HCl to a pH of 3 and mixed well for 30 minutes, then extracted with ether (3 x 25 ml). The organic materials were combined, dried (MgSO4), and then concentrated low pressure reduced which provided 7. g (91%) of 2- acid hydrobencenboronic acid in the form of a white solid with a r melting point of 15 ° -158 ° C. Methyl (4-bromophenyl) acetate (2.79 g, 12.2 mmol), tetrakis (tri-phenylsphine) palladium (O) was degassed. ) (170 m), 5 potassium phosphate (9.71 g, 45.75 mmol) and dimetho-ietane (50 ml) under nitrogen atmosphere in a 100 ml flask equipped with a reflux condenser. 2- Methoxybenzeneboronic acid (2.52 g, 18.3 mmol) in dimethoxyethane (5 ml) was added and the mixture was heated under reflux condition overnight, then mixed with 1: 1 sodium chloride / saturated ethyl acetate. (25 ml). The organic materials were separated, dried (MgSO 4), and then concentrated under reduced pressure. The residue was purified by flash chromatography (Si02, hexane 5 gradient to 3: 1 hexane / ethyl acetate) which yielded 2.21 g (75%) of (4- (2-Y * - hydroxypheni 1) phenylacetate) of methyl. Part C: Operated in the same manner as in part D of EXAMPLE 1, but using (methyl 4- (2-hydroxypheni 1> feni 1) acetate 0 which gave (4- (2- (2,3, 4, o-tetra-Q-acetyl-1-alpha-D-mannopi ranosi lo? I> feni 1) methyl phenylacetate with a yield of 8%. Part D: Operated in the same manner as in part E of EXAMPLE i, but the use of (4- (2- (2,3,4, or-tetra-Q-aceti 1-5 al-D-manopi r nosi lo? i> feni 1) methyl phenylacetate gave 4- (2- (alpha-D-mannopyranosylKi) pheni 1 → phenylacetic acid as a hygroscopic white solid.1H NMR: (300 MHz, DMSO-do) 7.02-7.50 (comp, 8H), 5.30 ( s, lH), 3.30-3.75 (comp, 12H) ppm IR (KBr): 3404, 1788, 1712, 148Ó, 1218, 1170, 1018, 752 cm- 1. Melting point: 65 -8 degrees C. Analysis : Cale for C20H2208. (C2HF302): 52.38% C, 4.59% H.

Y Found: 52.02% C, 4.52% H. EXAMPLE 3 ACID 3- (2- <ALFA-D-MAN0PIRAN0SIL0XI) PHENYL) BENZ0IC0, SALT LITHIUM Part A: Operated in the same manner as in part A of EXAMPLE 1, but by the use of 3-bromobenzoic acid, methyl 3-bromobepzole was obtained in a proportion of - * - 95%. Part B: It was operated in the same way as in part B in the EXAMPLE 1, but the use of methyl 3-bromobenzoate gave methyl 3- (2-methoxypheni-1) benzoate in a yield of 4%, with a melting point of 92 to 93 degrees.

C. Part C: It was operated in the same way as in part C of the EXAMPLE 1, but using 3- (2-methoxy-pip-1) bepzoate methyl was obtained 3- (2-hydroxypheni 1) methyl benzoate in a yield of 84%. Part D: It was operated in the same way as in part D of the EXAMPLE 1, but using 3- (2-hydrs? Ifepi 1) methyl benzoate was obtained 3- (2- (2,3,4, o-tetra-Q-acet i 1-alpha-D-mapop iranosi lox i) feni 1) methyl benzoate in an 85% yield Part E: In a dry 50 ml flask under a nitrogen atmosphere, 3- (2- (2,3,4,6-tetra-Q- aceti 1- Ifa-D-rX manopiranosi lox i) feni 1) methyl benzoate (2.18 g, 3.9 mmol) in methanol (20 ml) and was treated in one portion with sodium methoxide (250 mg) and the mixture was stirred At room temperature overnight, and then concentrated under reduced pressure, the residue was purified by flash chromatography (Si02, 7: 3 methyl chloride / ethanol) which gave 3- (2- (alf-D - * - mannopyranosi lo? i) feni 1) methyl benzoate in an 84% yield Part F: 3- (2- (methyl α-D-mannopyranosyl lo? i) phenyl) benzoate was dissolved (0.O62 g, 1.7 mmol) in aetonitrile (15 ml) An aqueous solution of lithium hydroxide monohydrate (0.12 g) was added. , 2.55 mmol in 1 ml of water) and the mixture was stirred at room temperature for 8 hours. The mixture was then diluted with additional acetonitrile (approximately 10 ml) and the Lithium 3-4- (2-al-Fa-D-mannoxy ranosi loxi) pheni 1) benzoic acid was presipitated. The solids were collected and dried and yield 0.514 g (94%) of product, melting point: 109-115 degrees C. 1H NMR: (300 MHz, DMSO-do) 8.11 (s, lH), 7.79 (d, J = 7Hz, 1H), 7. 20-7.40 (comp, 5H), 7.06 (t, J = 7 Hz, 1H), 5.43 (s, 1H), 5. 25 (br s, 1 H), 5.04 (br s, 1 H), 4.70 (br s, 1 H), 4.55 (br s, 1 H), 3.25-3.70 (camp, h) ppm. IR (KBr): 3384, 1560, 1405, 1389, 1111, 1057, 1020, 757 cm-1. Analysis: Cale for C19H190S, (H20), 1.8) LiOH): 51.4% C, 5. 189% H. Found: 51.62% C, 4.81% H EXAMPLE 4 ACID 4- (2- (ALPHA-MAN0PIRANOSILQXI) PHENYL) BENZOIC Part A: Operated in the same manner as in part A of EXAMPLE 1, but by The use of 4-bromobenzic acid gave methyl 4-bromabenzoate in a proportion of the 90%, with a melting point of 66-68 degrees C. Part B: It was operated in the same way as in part B in the EXAMPLE 1, but the use of methyl 4-romobenzoate gave methyl 4- (2-metho? I-pheni-1) benzoate in a yield of 51%. Part C: Operated in the same manner as in part C of EXAMPLE 1, but using 4- (2-methoxyphenyl) bepzoate methyl was obtained 4- (2-hydroxy f or 1) methyl benzoate in an A yield of 71%. Part D: It was operated in the same way as in part D of the EXAMPLE 1, but using 4- (2- (2,3-tetrahydroxy-phenyl) benzoate 5-methyl) 4- (2- (2,3,4,6-tetra-Q-acetyl 1-alpha-D-anspi ranosi loxi) was obtained. fepi 1) methyl benzoate in a 95% yield • Part E: Operated in the same way as in part E of the EXAMPLE 1, but using 4- (2- (2,3,4,6-tetra-Q-acet i 1-al-fa-IfcY D-mannopyranasi loxi) pheni 1) methyl benzoate acid was obtained 4- (2- (al fa-D-manopi ranosi loxi) feni 1) benzoic in a yield of 71%, with a melting point of 248-249 degrees C. 1 H NMR: (300MHz, DMS0-d6) 7.98 ( d, J = 8Hz, 2H), 7.61 (d, 15 J = 8Hz, - 2H), 7.30-7.40 (comp, 3H), 7.05-7.16 (comp, 1H), 5.36 (s, 1H), 4.90-5.05 (brs, 1H), 4.76-4.90 (brs, 1H), 4.65- 4.76 (brs, 1H), 4.40-4.58 (brs, 1H), 3.25-3.70 ( comp, 6H) ppm. IR (KBr): 3511, 3398, 2929, 1683, 1614, 1485, 1419, 1314, 20 1259, 1107, 1013, 986, 746 cm-1. Analysis: Cale for C19H2008.0.25 (H20): 59.92% C, 5.43% H.

Found 59.80% C, 3.25% H. EXAMPLE 5 ACID 3- < 2- (ALFA-D-MAN0PIRAN0SIL0 I FENIL) FENIL0 IACETIC0 -or Part A: 3-Bromophenol (2.84 g, 16.4 mmol) was dissolved in dimethylformamide (50 ml) in a 100 ml dry flask under nitrogen atmosphere. Sodium hydride (0.7 g of a 60% suspension in mineral oil, washed with hexane, 16.7 mmol) was added in portions and the mixture was stirred for 1 hour at ambient temperature. Ethyl bromoacetate (1.85 ml, 16.7 mmol) was added dropwise and the reaction was mixed overnight at room temperature. Approximately two thirds of the solvent was removed under pressure Y ^ 'reduced and the residue was mixed with water (150 ml) and extracted with methylene chloride (3 x 20 ml). The extracts were combined, washed with water (50 ml), saturated sodium chloride solution (50 ml), and then dried (MgSO4).

The solution was filtered and concentrated and gave 4.18 g (98%) of ethyl 3-bromophenyl iacetate. Part B: Was operated in the same manner as in part B in the EXAMPLE 2, but employing ethyl 3-bramophenyl iacefcate which obtained ethyl 3- (2- (hydra-ifynyl) phenylacyanate in a yield of 52%, Part C: Operated in the same way as in part D in the EXAMPLE 1, but using ethyl 3- (2-hydro? Ifenyl) phenylacyanate which obtained ethyl 3- (2- (2- (2,3,4,6-te ra- -ace il-alf-D-anop iranosi lo? i) feni 1) phenyloacetate in a yield of 69%.

-. Part D: Operated in the same manner as in part E in EXAMPLE 1, but using ethyl 3- (2- (2,3,4, or-tetra-Q-acet i 1- al fa-D-manap go nosi loxi) eni 1) feni la? iacet to obtain 3- (2- (a ifa-D-mannopyranosi lo) pheni l) phenoxy lox iacet to 5 in a yield of 82%, with a melting point of 58-60 steps C. 1H NMR: (300MHz, DMSO-do) 7.25-7.38 (comp, 4H), 7.06-7.15 (comp, 2H>, 6.97 (s, 1H), or.90 (ult, 1H ), 5.34 (mult, 1H), 4.70 (s, 2H), 3.80-4.40 (br s, 4H), 3.30-3.75 (comp, OH) ÍÓ r ppm. IR (KBr): 3404, 2943, 1788, 1737, 1478, 1424, 1220, 1173, 1068, 1016, 979, 755, 696 cm-1. Analysis: Cale for C20H2209. (H20) .1.1 (C2HF302): 48.50% C, 4. 60% H. 5 Found: 48.70% C, 4.21% H. EXAMPLE or / \ ACID 4- (2- (ALPHA-D-MAN0PIRAN0SIL0XI) PHENYL) FENIL0XSACETIC0 Part A: Operated in the same manner as in part A in he EXAMPLE 5, but using 4-bromofepol which obtained ethyl 4-bromophenylaxyacetate in a yield of 98%. Part B: It was operated in the same way as in part B in the EXAMPLE 2, but using ethyl 4-bromophene lo? -acetate which obtained ethyl 4- (2-hydro? Ifepi 1) phenyloacetate in a yield of 41%. , s, Part C: It was operated in the same way as in part D in the EXAMPLE 1, but using ethyl 4- (2- h idro? Ifeni 1) f or loxiacetata which obtained ethyl 4- (2- (2,3,4,6-tetra-Q-acetyl-alpha-D-mannoxy) ranxi) phenyl) phenyloxyacetic in a yield of 80%. Part D: It was operated in the same manner as in part E in EXAMPLE 1, but using ethyl 4- (2- (2,3,4,6-tetra-Q-acet i 1- to f-D-manopi ranos i loxi) feni l) feni lox iacet to that obtained 4- (2- (aD-manopi ranosi.loxi) feni 1) feni loxiacetata in a yield of 69%, with a melting point of 145-146 degrees C. 1H NMR: (300MHz, DMSO-do) 7.42 (d, J = 8Hz, 2H), 7.23-7.35 (comp, 3H), 7.07 (t, J = 7Hz, 1H), or.95 (d, J = 8Hz, 2H), 5.30 (s, 1H), 4.71 (s, 2H), 3.30-3.80 (comp, 10H) ppm. IR (KBr): 3418, 2930, 1739, 1521, 1486, 1240, 1219, 1110, 1068, 1013, 834, 756 cm-1. "" - Analysis: Cale for C20H2209.1.5 (H20): 55.43% C, 5.81% H. Found: 55.81% C, 5.54% H. EXAMPLE 7 ACID (3- (2- (ALPHA-D-MAN0PIRAN0SIL0XI) PHENYL) BENCIL0XIACETIC0 Part A: It was operated in the same way as in part A in EXAMPLE 5, but using 3-bromobenzylcocoal that obtained ethyl 3-bramabenz and loxiacetate in a yield of 40% .Part B: It was operated on way than in part B in EXAMPLE 2, but using ethyl 3-bromabenz lox iacet that obtained ethyl 3- (2-hr-i-d-i-n-1) benz i loxiace a to in a yield of 34%. Part C: It was operated in the same way as in part D in the EXAMPLE 1, but using 3- (2-hdrox i fem 1) bene i lsx lacet to obtain ethyl 3- (2- (2,3, 4,6-tetra-Q-acet i 1-al fa-D -manop i ranosi lo :, i) feni 1) benc i lox laceta to a yield of 74%. Part D: It was operated in the same way as in part E in the EXAMPLE 1, but using ethyl 4- (2- (2,, 4,6-tetra-0-acet 11-al-Fa-D-maf »c.p i ranosi la. I) feni 1) benc? loxiacetate that obtained 3- (2- (a-lfa-D-mannoprospoxy) phen?) benzyl oxyacetic acid in a yield of 30% with a melting point of "7 ~ 78 degrees C, 1 H NMR: (300MHz, DMSO- do) 7.20-7.51 (comp, 7H), 7.15 (mult, 1H), 5.32 (s, 1H), 4.11 (s, 2H), 3.25-3.75 (comp, OH), 3.47 (sm 2H) ppm. IR (KBr): 3417, 2 < 3B, 1787, 1734, 1220, 1172, 1112, 1013, 977, 754 CHi-l. MS (FAB): 443.2 -m + Na) + Analysis: Cale for C21H2909. (C2HF302) .0.5 (H20): 50.83% C, 4. 82% H. Found: 50.59% C, 4.74% H. EXAMPLE 8 N- (4- (2- (ALPHA-D-MAN0P IRANOSI LOX I) FENI L) BENZ0I L) SL IC INA ^ Part A: Acetone (5.6 l) and di metox iprop not added (5. or ml) to 4- (2- (al-Fa-D-anop i ranoxi lo? I) feni 1) benzoic acid (0.54 g, 1.43 mmol) to form a heterogeneous mixture. A catalytic amount of p-toluenesulfonic acid hydrochloride was introduced and the reaction was stirred at room temperature for 45 minutes, when a clear, homogeneous solution was obtained. The solvent was removed in vacuo and the oily yellow residue was taken up in ethyl acetate, washed with saturated sodium bicarbonate and then in saturated sodium chloride, dried (MgSO 4) and concentrated in vacuo to give 4- (2- (2 , 3: 4, 6-d iQ- isoprop i 1 ideno) 1 f - D-hand pi ranos i loxi) feni 1) benzo ico (0.70 g). Part B: A solution of 4- (2-2, 3: 4, 6-di-Q-isoprop and 1 i-depo) acid to crude fa-D-manno-ranosi loxi) phenyl) benzoic acid (0.70 g) in dichloromethane (4 ml) was added to a paste of And lysine ethyl ester hydrochloride (0.20 g, 1.44 mmol) and triethylamine (0.40 mL, 2.88 mmol) in dry dichloromethane (3 mL). N-hydrox isucc inimide (0.16 g, 1.44 mmol) and N, -d -cyclohexy lc rbod i imide (0.32 g, 1.55 mmol) were added and the reaction mixture was stirred under nitrogen at room temperature for 4 hours . The preshaped dicyclohexyl 1 was removed by filtration and the filtrate was diluted with dichloromethane. The resulting solution was washed with water, 1N HCl, brine and bicarbonate. 05 saturated sodium, then dried (MgSO.sub.4) and concentrated under reduced pressure to provide 0069 g (89% for two steps) of ethyl ester of N- (4- (2- (2, 3: 4, 6-di. -Q- isaprop i 1 idena) alpha ~ D-mapop go no i lo) phenyl) benzayl) glycine 5 Part C: ethyl ester of N- (4- (2- (2, 3: 4, or-di -Q-isapra i 1 idena) alpha-D-anapi ranosi loxi) feni 1) benzoi 1) glycine (0.69 g, 1.28 mmol) was dissolved in tetrahydrofuran (2.5 ml). An equal volume of 1 N HCl was added and the reaction mixture was stirred overnight. 2 N sodium hydroxide (2 ml) was added and the reaction was applied for an additional S hours. The solution was then acidified again to a pH of 4.5 with 1 N HCl and the product was isolated by preparative reverse phase HPLC on a Dyna ax 300 &C18 column. 5 microns (21 mm ID? 25 cm). A gradient of 5-50% solvent B was performed for 20 minutes at a flow rate of 10 ml / min, where solvent A was composed of 5% acetonitrile / water with 0.1% TFA and solvent B It was composed of 95% acetonitrile / water with 0. 1% of TFA. The effluent was monitored at 254 nm. The 0 pure fractions were combined and lyophilized to yield 0.33 g of N- (4- (2- (al-D-manop iranosi loxi) phenyl) bensoi 1) glycine. 1H NMR: (300MHz, D20) 7.85 (d, J = 7.8, 2h), 7.61 (d, J = 7.8, 2H), 7.41 (, 2H), 7.32 (d, J = 9.0, 1H), 7.20 (t , J = 6.9, 7.8, 1H), 5.48 (3, 1H), 4.11 (s, 2H) 3.94 (s, 1H), 3.60 (br, 4H), 3.28 (br m, 1H). IR (KBr): 3404, 2938, 1734, 1637, 1544, 1220, 1107, 10OÓ cm-1. Melting point: 127-129 degrees C Analysis: Cale for C21H23N09.1 / 5 (CF3C02H); 50.34% C, 5.13% H, 3.07% N. Found: 56.36% C, 4.93% H, 2.98% N. EXAMPLE 9 N- (4- (2- (ALPHA-D-MAN0PTPAN0SIL0XI> FENIL) BENZOIL> -D-FENILALANI A Part A : A paste of 4- (2- <, 3:, 6-Di-Q-isoprop i 1 ideno-aD-manop i rano i loxi) phenyl) benzoic acid (0.25 g, 0.55 .mmol) and hydrochloride was formed of D-phenylethyl methyl ester (0.13 g, 0.60 mmol) under dry ethanolamic atmosphere (2 ml), N-met il arfolin (0.13 ml, 1.18 mmol), hydroxy ibenzotriazole hydrate (74 g) was added. m, 0. 55 mmol) and l- (3-d imet i laminapiopi 1) -3-ethylcarbodiimide hydrochloride (0.26 g, 1.35 mmol) were added and the reaction was stirred at room temperature for 2 hours. Ethyl acetate was added and the solution was washed with water, 1N HCl, saturated sodium bicarbonate solution, brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by chromatography on silica gel (2: 1 hexane: ethyl acetate) to provide ester Y-. I ico of N- (4- (2- (2, 3: 4, 6-d iQ- i soprop i 1 ideno-a l fa-D- manap iranasi loxi) feni 1) benzai 1) -d- feni lalanina (0.26 g, 7%) in the form of a white foam. Part B: Operated analogously to part C of E. EXAMPLE 8, but using an HPLC gradient of 20-80% solvent B in 20 minutes that obtained N- (4- (2- (al fa-D - manapi r us i loxi) feni l) benzoi 1.) -D-feni lalanina with a yield of 46%; melting point = 116-119 degrees C; IR (KBr): 3424, 2972, 1738, 1642, 1539, 1361, 1215, 1109, 1070, IV and 1013 cm-15 H NMR (300 MHz, CD30D): delta 7.77 (d, 2H, J = 8.4), 7.54 (d, 2H, J = 8.4), 7.29 < m, 9H), 7.10 (t, 1H), 5.41 (s, 1H), 3.80 (br s, 1H), 3.O7 (m, 4H), 3.49 (br,, 1H), 3.35 (, 1HO, 3.12 ppm (dd, 2H, J = 13.3, 9.6); Mass spectrum (Cl): m / z = 524, 362, 163, analysis: step 5 for C28H29N09, 64.2% C, 5.6% H, 2.7% N; found: 64.2% C, 5.6% H, 2.4% N.f, EXAMPLE 10 Acid 3- (2- (6-az ida-6-deox i-a 1 fa-D-manop i rano i loxi) phenyl) phenyl acetic. 0 Part A: 3- (2- (2,3,4,6-tetra-Q-acet i 1-a Ifa-D-manop i ranasi lax i) feni 1) phenylacetate methyl (3.96 g, 6.9 mmol, from part E, EXAMPLE 2) in methanol (50 ml), sodium ethoxide (100 mg) was added and the solution was stirred at room temperature for 2 hours. The reaction mixture was neutralized with an exchange resin Ion-ex-5 (form H- +) was filtered and concentrated in vacuo. Chromatography (silica, 9: 1 CHC13: m tanal) gave 3- (2- (alpha-D-manop i ranosi laxi) phenyl) phenylacetate methyl (2.8 g), quantitative yield equal to about 100%)). Part B: Dissolve 3- (2- (al fa-D-anap iranssi lox i) feni 1) phenylacetate methyl (1.8 g, 4.6 nmol) in 2, -dimethoxy propane (30 ml) and acetone ( 30 ml), p-toluenesulonic acid (100 mg) was added and the solution was stirred at room temperature overnight. The reaction mixture was poured into saturated sodium bicarbonate and the product was extracted with ethyl acetate. The combined extracts were dried (MgSO4) and concentrated in vacuo. Purification by chromagraphy (silica, eluent 6: 1 hexane: ethyl acetate) provided 3- (2- (2,3: 4,6-di-Q-i-1-idep-1-ide-a-Dm-no-i-i-i-i) i loxi) phenyl) phenylacetate of (meth) 1o (1.87 g, 84%). Part C: 3- (2- (2,3: 4, o-di-0-? Soprop i 1 ideno-a lf - D-manopi ranosi loxi) feni 1) phenylacetate methyl (1.53 g, 3.2) was dissolved nmol), in methanol (50 ml), p-toluenesulfonic acid was added (100 mg) and stirred at room temperature until t.l.c. (eluent 9: 1 CHC13: methanol) showed an optimal conversion for monoacetanide. The reaction was quenched by the addition of a small volume of saturated sodium bicarbonate and then concentrated under reduced pressure. The residue was / _ divided between ethyl acetate and water and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed once with saturated sodium chloride, dried over magnesium sulfate and concentrated under reduced pressure. Chromathography (silica, eluent 9: 1 CHCl 3: methanal) yielded 3- (2- (2, -Q- isoprop i 1 ideno-a 1 fa- D-manop i ranosi lax i) pheny1) phenylacetate methyl (0.92 g, 55%). Part D: 3- (2- (2, 3-Q-i soprop i 1 ideno-a 1 fa-D- H 0 0 anopyranos i lo:.?) Feni 1) feni laceta to methyl ( 6.37 g, 14.3 nmol) in pipdine (100 ml) and the solution cooled to 03 ° C. P-Toluensulphonyl chloride (5.5 g, 28.9 nmol) was added followed by 4-d imet i laminopi pdine (100 mg) and the solution was stirred at room temperature overnight. After cooling to 0 ° C, acetic anhydride (5 ml, 53 nmol) was added and the solution was stirred at room temperature for 24 hours. The reaction mixture was diluted with ethyl acetate and washed with dilute hydrochloric acid to remove the pipdin. The organic layer was then washed with dilute sodium bicarbonate and saturated sodium chloride, which layer was dried (MgSO 4) concentrated in vacuo. This yielded 3- (2- <4-Q-acet i 1-2,3-0-? Soprop? 1? Deno-6-Qp-toluensul fani 1-to the fa-D-manopíranos i loxi) feni l ) methyl phenyl acetate (9.19 g, quantitative yield (100%)).

P-trte E: 3- (2- (4-0-acet i 1-2, 3-0- isoprop i 1 ideno- 6-Qp-taluensulfoni lo ~ 1 fa-D-manop i anosi loxi) feni was dissolved 1) Pheni-1-methyl acetate (9.19 g, 14.4 nmol in dimethyl formamide (100 ml), sodium iodide (4.3 g, 29 nmol) was added and the mixture was heated to 110 ° C. for 6 hours, after cooling to room temperature, The majority of DMF was removed in vacuo and the residue was partitioned between ethyl acetate and water.The organic layer was washed with water, a diluted solution of sodium thiosulfate, water, saturated sodium chloride, said layer was dried (MgSO4) and concentrated The chromatography (silica) eluent 2: 1 he? apa: ethyl acetate) gave 3- (2- (4-0-ace 11-6-? odo-6-deo? i-2, 3- 0- isoprop 11 idens-al-fa-D-manop i ranks i loxi) fem 1) methyl phenyl acetate (6.42 g, 75%). Part F: Prepared 3- (2- (4-Q-acet i 1-or-az ido-ó-dea?? -, 3-Q-isoprop 11 ideno-a 1 fa-Dm nop ir nasi lax?) methyl phenyl) phenylacetate from 3- (2- (4-Q-acet 11-6-iodo-6-dea? i-2,3-Q-isopropy 1 ideno-al-fa-D-manap) nos i lox?) fep? l) methyl phenylacetate and sodium azide in a yield of 93% using a procedure analogous to Part E, of this example, and sodium azide was used in place of sodium ladide. Part G: 3- (2- (4-Q-acetyl-6-azide-o-deoxy-2,3-Q-isopropyl 1 ideno-al fa-D-manap ira i laxi) feni was dissolved Methylacetate feni (0.208 g, 0.41 nmol) in methanol (6 ml) and water (2 ml). Concentrated hydrochloric acid was added (3 drops "1 and The solution was stirred at room temperature for two days. The solution was made basic with a dilute sodium hydroxide solution and stirred at room temperature for one hour. After neutralization with dilute hydrochloric acid 5, the solution was concentrated in the chair. The residue was stirred with methanol and the white solid was removed by centrifugation. The solution was concentrated under reduced pressure and the residue was absorbed in 5% acetonil / water with 0.1% lupoacetic acid. \ After adjusting the pH to 3.5 using diluted hydrochloric acid, the orodirt-o was purified by reverse phase HPLC preparation on a Dynamex C18 column (.5 - .. microns (21.4 • 250 mm) at a flow rate of 10 l / mip An elution gradient of 20-80% solvent B was used 15 for 30 minutes, with solvent B composed of 95% acetanitide / water with 0.1% trifluoroacetic acid and solvent A composed of 5% acetonitoplo / water with 0.1% lumoacetic acid. The eluant was monitored at 254 nm, and the pure fractions were combined and 0 lyophilized to provide methyl 3- (2- (6-az? Da-o-deax? -aD-manap irapasi lo i) feni 1) feni lactic, (44 m, 26%); d) H NMR (300 MHz, D20 / DMSO-do) 3.3-3.4 (, 3H, OH), 3.55 (dd, J = 9.6, 8.4, 1, H, CH2N3), 3.62 (dd, J = 9.6, 2.7 , 1 H, CH2N3), 3.73 (s, 2 H, CH2C02H), 3.96 (m, 1 H), 4..6-5.0 5 (m, 3 h), 5.46 (s, 1 H), 7.14-7.50 (m, 8 H, arom.). IR (kBr: _._ cm-1): 3421, 2101, 1717; mass spectrum m / e (CI: CH4) 229, 183 (100%). Analysis calculated for C20H21N307 * 0.3 (CF3C02H): C; 55.9; H, 4.9 N, 9.6: found: C, 56.1; H, 4. 6; N, 9.5%. EXAMPLE 11 Acted 3- (2- (6-am? No-or-deox? -al f -D-m nope ira i i?) Feml) f lacético, hdracloruro. Part A: stirred 3- (2- 4-Q-acet i l-6-ra ida-o-deo? -2, 3-Q- issaprop il ideno-a 1 aD-manap i raposi lox i) feni l) Pheni-1-acetate-methyl (1.26 g, 2.5 nmol, from part F, EXAMPLE 1 <> with sodium methylene chloride (100 ml) in methanol (15 ml) at 1-p.t. overnight, the solution was neutralized with an ion exchange resin Da? -. ex-50 (form H +), filtered and concentrated in vacuo Chromatography (silica, eluent 3: 1 he: -anine: ethyl acetate) provided 3-2- (6-az? da-6-deox? -2,3-Q-isoprop i 1 ideno-lf aD-manop i ranos i lax i) f) l) fen? laceta to met i lo (1 .02 g, 88%). Part B: 3- (2- (6-az? Da-6-deox? -2, 3-Q-isoprop i 1 ideno-a 1 fa-D- manapi ranasi loxi) ) feni 1) methylmethacrylate (0.79 g, 1.7 n a) was dissolved in methanal (20 ml), Raney nickel (0.56 g) was added and the mixture was stirred at room temperature for 2 hours. and concentrated in vacuum chromatography (silica, eluent 9: 1 CHC13 / methanol) provided 3- (2- (6-am? no-ó-deox? -2, 3-Q- isoprop i 1 ideno-to f -D-manop i ranosi lox i) feni 1) phen11 methyl aceto, 0.52 g (69%). Part C: 3- (2- (6-am? No-6 ~ deox? -2, 3-Q-isaprop 111deno-a-lfa-D-mannofan i lox?) Fen? L) fen? Lacetate was dissolved methyl (77 mg, 0.17 nmol) in methanol (5 ml), Phonic acid p-taluensu 1 (40 mg, 0.21 nmol) was added and the solution was stirred at room temperature overnight. Aqueous sodium hydroxide (2 M, 0.4 ml) was added and the solution was stirred ? for 5 minutes before acidifying with S i do t < dilute hydrochloric The product was purified by reverse phase HPLC on or off on a CIB Dyna column at 30 microns (21.4 25 ') mm at a flow rate of 10 ml / in. An elution gradient was used. of 10-40% solvent B for 25 minutes, solvent B consisting of 15 acetonitp at 95% / water with 0.1% luoroacetic acid and solvent A was composed of 5% acetanitrile / water / ^ with luaroacetic acid tnf to] 0.1%. The effluent was monitored at 254 nm, and the pure fractions were combined and concentrated in vacuo. Water (5 ml) 0 and dilute hydrochloric acid (0.2 ml) were added and the mixture was concentrated again. This procedure was repeated once more with hydrochloric acid and once with water. The residue was then dissolved in water (5 ml) and lyophilized to provide acid 3- (2- (6-amino-o-deo: i-ai fa-D- manop i ranosi .ox i) feni.1) phenyl acetic acid, hydrochloride (50.3 mg, 74%). EXAMPLE 12 Ac left N- (3- (2- (to fa-D-manop i ranosi loxi) feni 1) benzo i 1) -L-glutamic. Part A: 3- (2- (2,3: 4,6-Di-Q-isoprop i 1 ideno-l-D-mano i ranosi lox i) feni l (benzoic acid in a form analogous to that part) was prepared. A of EXAMPLE 8. Part B: Operated analogously to Part A of the EXAMPLE, but using ester hydrochloride gave it methyl L-glutamic acid and acid 3- (2- (2, 3: 4, 6 -IQ- i soprop il idena-a lf -D- anopyranos i loxi) feni 1) benzoic was obtained dimethyl ester of N- (3- (2- (2, 3: 4, 6-d iQ- soprop i 1 ideno-a 1 fa-Dm pop i ranosi lo i) phenyl) benzoi 1) -Luthamic with a yield of 89% Part C: Operated analogously to Part C of EXAMPLE 8, but using a HPLC gradient of 10-60% solvent B in 20 minutes was obtained N- (3- (2- (aD-manop iranosi lo? i) feni 1) benzoi 1) -L-gl.utám? eo with a 19% yield, melting point = 109-112ßC; IR (.KBr): 3390, 2938, 1717, 1635, 1539, 1416, 1217, 1100, 1059, 1011 cm-1; 1 H NMP (300 MHz, D20) : O 7.82 < s ,, 1H ), 7.73 (d, 1H, J = 7.8), 7.65 (d, 1H, J = 7.5), 7.53 (t, 1H, J = 7.5), 7.37 id, 2H, J = 7.8), 7.29 (d, 1H) , J = 8.1), 7.17 < t, 1H, J = 7.2), 5.45 -s, 1H), 4.58 iO, 1H, J = 4.8), 3. ^ 2 (s, 1H), _ 3.57, m, 6H), 3.19 (br, 1H); mass spectrum m / e (CI: CH4) 344, 163; Analysis: cale. for C24H227N011 * 1/3 (C2F3H02), 54.5% C, 5.1% H, 2.6% N; found: 54.4% C, 4.8% H, 2.6% N. 5 EXAMPLE 13 ACID 3- (2 - (- 6 (CARB0XI ETHYTH0) -6-DE0XI-ALPHA-D- MANOPYRANTS I LO I) PHENYL) PHENYL CENTIC Part A Sodium hydride (60 wt% disp, 0.14 g, 3.4 m al) was washed with sib, tet rah idro furan (5 ml; 1C < degasified the mixture. Tiogl icol ato de mat 11 (0.4 ml, -.5 mmol) was added, followed by a solution of 3- (2- (4-Q-i-Iet-1-6-deo-i-o-Lodo-2). , 3-Q- i soprap i 1. ídeno-a 1 fa-D- anap i ranosi lox i) feni l) feni 1 methyl acetate (0.83 g, 1.4 m ol., .Part E, EXAMPLE 10) IN thf (10 mi) The solution was The mixture is then stirred again and then stirred at room temperature for 72 hours. The reaction was turned off with water "- and then divided between ethyl acetate and water. The organic layer was washed with diluted tea, diluted water, and saturated sodium chloride. After drying (MgSO 4), the solution was concentrated in vacuo. The chromium or raffi (silica, eluent 2: 1 hexane: ethyl acetate) yielded 3- (2- (4-Q-ace 11-6-deo) i-o-iodo-2, 3-Q-isoprop i 1 ideno-a lf -D- manop i ranosi lax i) feni 1) methyl phenol (0.7 g, 87%). Part B: 3- (2- (4-Q-acet i 1-6- 5 cbo ethoxy et i 1 a) -6-deo? I-2, 3-0- isoprop and 1 ideno- D- manop i ranasi loxi) feni 1) methyl phenylacetate (0.56 g, 1 mmol) in methanol (30 ml), dilute hydrochloric acid (2 ml) was added and stirred at room temperature overnight, then heated to reflux for 30 minutes. After cooling to room temperature, sodium hydroxide (2 M, 5 ml) was added, and the solution was stirred for 10 minutes. The solution was neutralized using dilute hydrochloric acid and then cooled in vacuo. The residue was stirred with methanol and the white solid removed by centrifugation. The solution was concentrated in vacuum and the residue absorbed in acetamtrila 5% / water with Sci to trie 1 oruacético to 0.1%. After adjusting the pH to 3.5 using dilute hydrochloric acid, the product was purified by reverse phase HPLC preparation on a Dynama C18 column: - 300 μm, 5 microns (21.4 .. 250 mm) in a flow regime of 10 ml / min. An elution gradient of 20-80% of solvent B was used for 20 minutes, solvent B was composed of 95% acetani tri-l / water with 0.1% t-chloroacetic acid and solvent A was composed of 5% acetoni. p / water with 0.1% trichloroacetic acid. The effluent was anitored at 254 nm, and the pure fractions were combined and lyophilized to provide 3- (2- (6- (carbaxy et i lt IO) -6-deaxy-al fa-d-ana i ranosi loxi) feni 1) phenylacetic (0.40 g, 83%); 1 H NMR (300 MHz, D 20): delta 2.60 (dd, J = 14.1, 8.4, 1H, O-H), 2. 84 (dd, J = 14.1, 1.8, 1H, OR'-H), 3.04 and 3.30 (both d, J = 14.4, 1H, SCH2C02H), 3.3-3.6 (, 3H), 3.70 (s, 2H, CH2C02H) , 3.94 (m, 1H), 4.6-5.0 (m, 3H), 5.48 (s, 1H, 1-H), 7.14-7.50 (m, 8H, arom.); IR (, -Br: cm-l): 3396, 1710; 5 mass spectrum m / e (CJ: CH4) 465 d%), 393, 229, 283 (100%). Analysis: calculated for C22H2409S, 0.8 (H20): C, 55.2; H, 5.4. Found: C, 55-25; H, 5.25%. EXAMPLE 14 ACID 2-Í3-Í2-ÍALFA-D- MANOP I PANOLI LOX I '< FENI L 'FENI L) ETANESULFONICO Part A: e dissolved 3- (3- (,: 4,6-d? ~ Q-? Saprap 11 ideno-al f a- D-manop i ranos i lo i. Feni 1) Methyl methoxylated pheni (1.28 g, 2.6 mmol, starting from part B, EXAMPLE 10) in ether (50 ml) was cooled to 0 degrees C. 5-lithium aluminum hydride (1 M) was added dropwise. THF, 50 mL, 5 mmol) and quenched by careful addition of water, followed by Acid A ^. sulfuric acid diluted to ice temperature. The organic layer was washed with water, then with a saturated sodium bicarbonate solution, dried (MgSO 4) and concentrated in vacuo to provide 2- (3-2- (2, 3: 4, 6-d) -Q- isoprop i 11 deno-al fa- D-mannopyrosi laxi) pheni 1) pheni 1) ethanal (1.13 g, 94%) Part B: 2- (3- (2- (2,3: 4,6- Di-Q-isoprop 11 ideno-alpha-D-manoi anos i lox i) feni 1) phen íl) ethane 1 (0.73 g, 1.6 mmol) in di-chloromethane (50 ml) and cooled to 0 degrees C. Added 5 triethylamine (0.33 ml, 2.4 mmol), followed by chloride '8 metansul foni 1 o (0.15 m, 1.9 mmal). After 5 minutes at 0 degrees C, the reaction mixture was diluted with di-chloromethane and washed with dilute hydrochloric acid, water and a saturated solution of sodium bicarbonate, dried (MgSO 4) and concentrated in vacuo to provide 1-Q- etansulfanata of 2- (3- (2- (2,3: 4,6-d? -Q-? saprap? 1 ideno-alpha-D-manop Iranosi lo1- i) pheni 1) pheni 1) ethanol (0.77 g , 90%). Part C: 1-Q-metansul fon ta of 2- (3- (2- (2,3: 4,6-di-Q-iso rop il denafd aD-anap i rap si lox i ^ feni was dissolved. 1 '<feni 1) ethanol (0.22 g, C4 mmol) in ethanol <5 ml., Potassium thioacetate (0.1 g, 0.88 mmol) was added and the mixture was heated to 80 degrees C for 30 minutes. After cooling to room temperature, the reaction mixture was diluted between ethyl acetate and water, the organic layer was washed twice with water, dried < MgSO4) and concentrated in vacuo. Chromatography (silica, eluent 2: 1 hexane: ethyl acetate) yielded 2-mereapta- S < RTI ID = 0.0 > Z- (2- (2, 3: 4,6-d? -Q-? Soprop? L ideno-alpha-D-mannopyranasi loxi) pheni 1) pheni 1) ethanol (0.17 g, 80%). Part D: 2-mercapto- (3- (2-2.3: 4,6-di-Q-isaprapi 1 idena-to fa-D-manop iranosi loxi) feni 1) feni 1) was dissolved. Ethane (0.15 g, 0.29 mmol) in methanol (1 ml). An oxone solution (approximately 1 meq / ml in methanol / water, 1.5 ml) was added dropwise at room temperature for 90 minutes. After -i. stirring for 7 days, another part of an oxone solution (1 ml) was added for 60 minutes and the stirring was continued for 3 additional days. The product was isolated by reverse phase HPLC preparation on a C18 Dynamax 300 column. 5 microns (21 and 250 mm). A gradient of 0-70% solvent B was performed for 20 minutes at a flow rate of 10 ml / min, where solvent B was composed of 95% acetonitrile / water with 0.1% trifluoroacetic acid and the solvent A was composed of l ?. 5% 'acetopy tri lo / water with 0.1% trichloroetic acid. The flux was monitored at 254 nm, and the pure fractions were combined and 3 lyophilized to provide 2- (3- (2-al fa-D-manapiranosi lax i) pheny1) ethanesulfonic acid; 1 H NMR (300 MHz, D 20): delta 7.36 m, 8 H), 7.17 (t, 1 H, J = 7.5), 15 5.44 ís, 1H), 3.93 (s, 1H), 3.61 ím, 1H), 3.57 (, 4H), 3.25 (br m, 1H), 3.10 ppm < m, 4H); mass spectrum m / e (CI: CH4) • i-- 279, 163; Analysis: calculated for C20H24S09.2 (H20), 50.4% C, 5.9% H; Found: 50.4% C; 6.0% H. EXAMPLE 15 20 ACID N- (4- (2- (ALPHA-D-MAN0PIRAN0SIL0XI) PHENYL) BENZ0IL) -L- GLUTAMIC0 Part A: Operated analogously to Part A of EXAMPLE 9, but use of dimethyl ester hydrochloride of L-glutamic acid provided dimethyl ester of N- (4- (2- (2,3: 4,6-d? -Q-isopropyl) ideno-lfa-D- BO manop i ranosi lox i fem 1) benzo? 1) -L - g3 utAmico in a yield of 89%. Part B: Operated in an analogous manner to Part C of EXAMPLE 8, but the use of an HPLC gradient of 10-60% of solvent B for 20 minutes yielded acid N-Í4-Í2- a If -D -mans i rano i laxi) feni 1) benzol 1) -L-lutA ica in a yield of 43%; melting point = 118-121 degrees C; 1P í. Br): 33 ^ 0, 2938, 1717, 1635, 1539, 1477, 1217, 1107, 1059, 1011 cm-1; H NMP (300 MHz, CD30D): from to 7.80 id, 2H, J = 0 '8.7), .55 f-J, 2H, J = 8.4), 7.35 < m, 2H), ~? . 1.0 (d, 1H, J = S.), ".18 't, 1H, J = -5), 5.46 ís, 1H), 4.58 (dd,, J = 9. 9, 5. "" », 3.93 ís, 1H), 3.60 um, 5H), 3.24 √br, 1H), 2.53 ít, 2H, J = 7.2), 2.27,, 1H), 2.12 ppm (m, 1H; Esp of mass m, 'and íCI: CH4) 344, 163; Analysis: calculated for C24 5 H27N0116, 4, 1/4 (C2F3H02), 54.0% C, 5.1% H, 2.6% N; found: 53.7% C, 5.1% H, 2.4% N. / r_ EXAMPLE 16 N- (4- (2- (ALPHA-D-MAN0PIPAN0SIL0 I) PHENYL) BENZ0IL) -BETA-ALANINE Part A: Operated in a form analogous to Part A of EXAMPLE 9, but the use of beta- (alanine ethyl ester hydrcloride provided N- [4- (2- (2,3: 4,6-d- Q- isoprop i 1 ideno) ethyl ester -alfa-D-manap irano i lox? fen? l) benza? l) -be-alanine in a yield of 58% Part B: Operated in a manner analogous to Part C of EXAMPLE 8, but employment of a HPLC gradient of 0-50% of solvent B for 20 minutes yielded N- (4-y2-a1 f -D-manapi ranos i lax i) feni 1) benzo? 1) -beta-alanine in a yield of 53%; melting point = 101-104 degrees C; IR (KBr): 3397, 2938, 1717, 1635, 1539, 1484, 1217, 1107, 1066, 1011 cm-1; 1H MPN (300 MHz, CD30D): delta 7.75 (d, 2H, J = 8.1), 7.54 id, 2H, J = 7.8), 7.35 (m, 3H), 7.19 (t, 1H, J = 7.5), 5.47 (s, 1H), 3.93 ís, 1H), 3.64 ím, 7H), 3.26 íbr, 1H), 2.ó < ? ppm (t, 2H J = 6.4); Mass spectrum m / e iCl: CH4) 448, 286, 163; Analysis: calculated for C22 H25N09, l / íC2F3H02), 56.1% C, 5.3% H,. % N: found: 56. 1% C, 5.1% H, 3.0% N. EXAMPLE 17 ACID 3-y3-αALFA-D-MAN0PIPAN0SIL0XIMETHYL) PHENYLACETICUM Part A: 3-Bromobepcyl-1-yl alcohol (2.0 g, 10.7 mmol) was dissolved in THF ( 50 ml) in a dry 100 ml flask washed with nitrogen. The mixture was cooled in a dry ice / acetone bath. N-Butyllithium (11 ml of a solution) was added 2. 13 M in hexane, 23.5 mmol) the reaction was heated at room temperature for one hour, then cooled in an ice water bath. Trimethyl borate (1.3 ml, 11.2 mmol) was added and the mixture was stirred at room temperature overnight, then treated with 2N aqueous HCl to a pH of 2, and stirred for 3 hours. Brine (15 ml) was added and the mixture was extracted with ethyl acetate (3 x 15 ml). The organic materials were combined, dried (MgSO.sub.4) and then concentrated under reduced pressure which afforded 3- h idrox imet i lbencenboron ico acid (98%) as a crude oil. 3-Hydroxymethyl Ibencenbaronic acid (1.8 g, 11.8 mmol), 3-bromof or lacetic acid (2.55 g, 11.8 mmol), tribasic potassium phosphate, (7.54 g, 35.5 mmol), DMF (55 mL) were degassed. , and water (20 ml) under nitrogen atmosphere in a flask A 250 ml equipped with a reflux condenser. B i s chloride (rifeni 1 phosphine) p] a io (11) (0.17 g, 0.24 mmol) was added. The mixture was degassed under a nitrogen atmosphere, and heated to 90 degrees C overnight, then acidified with 2N HCl, mixed with brine (15 ml) and extracted with methylene chloride (3). 15 ml). The organic materials were combined, dried (MgSO.sub.4), and then caneentered under reduced pressure which yielded 3.0 grams of 3- (3-hydroxy-1-phenyl-1-phenylacetic acid). (3-hydro? Imeti lfeni 1) phenylacetic (3.0 g, 12.4 mmol), methanol (50 ml) and concentrated sulfuric acid (10 drops) under reflux overnight in a 100 ml flask, quenched with a saturated bicarbonate solution of sodium, diluted with water (10 ml), quenched with ethylene chloride (3 x 15 ml), washed with brine (1 x 15 ml), dried (MfS04), and concentrated under reduced pressure.

The residue was purified by flash chromatography (S? 02, 5: 1 / hexane: ethyl acetate) which gave 0.90 grams (30% 3-bromof or lactic acid) of 3- (3-hydrosyl and 1-phenyl) methyl entalacetate. 5 Part B: 3- (3-hdro? Ímet i 1 feni 1) feni lacetats was dissolved (0.87 g, 3.4 mmol) in 1,2-d-icro-aroetane (17 ml) in a dry 50 ml flask. D-mannose pentaacetate (1.66 g, 4.24 mmol) was added in one portion, then boron trichloride stearate (3.46 mL, 31.9 mmol) was slowly added. The mixture was v, stirred under nitrogen overnight at room temperature, then mixed with H20 (5 ml). The organic material was separated and the aqueous part extracted with methylene chloride (3 < 10 ml). The extracts were combined with the original organic fraction, dried (MgSO4), and then 15 concentrated ba or reduced pressure. The residue was purified or flash chromatography (S? 02, elution of hexane gradient: ethyl acetate / 3: 1) which gave 1.50 grams (5) of 3- (3- (2,, 4, 6-tetra -Qacet i 1- l fa-D- manop i ranasi lmet 11) feni 1) phenylacetate methyl ester contaminated with a small amount of unreacted D-mannose pentaacetate that coeluted with the product. Part C: 3-3-, 2,3, 4,6-tetra-Q-acet was dissolved? 1-a-fa-D-anopy ranosi lmet 11) fem l) methyl phenylacetate (1.0 g, 1.7 mmol) in acetonitoplo (10 ml) in a 50 ml flask, and treated with a solution of hydrous monohydrate. ? ids of lithium λ 72 g, 17.0 mmol) in water (8 ml). The mixture was stirred at room temperature overnight and then acidified to a pH of 3.5 with concentrated hydrochloric acid. The mixture was concentrated under reduced pressure and the residue was purified by HPLC (reverse phase C18, 10-70% gradient elution of acetomthole in water (0.1% tricaclatic acid) onitoreated at 254 nm) which gave acid 3- (3- (a 1 fa-D-manop i ranasi loxi ei 1) feni 1) phene lactic acid ≥50 g, 73%); melting point 74-75 degrees C; 1H NMP: (300 MHz, DMSO-do) 7.20-7.60 (comp, 8H), 4.73 < d, 2H, J = 12), 4.71 (s, 1H), 4.50 id, 2H, J = 12), 3.25-3.75 (comp, 11H plus water) ppm; IP (Br): 3394, 2934, 1715, 1366, 1220, 1130, 1060 cm-1; Analysis: calculated for C21H2408.0.15 (C2HF302): 0.69 C, 5.77 H; found: 60.60 C, 5.99% H. Part D: 3- (3- (a1 fa-D-manop i ranosi laxi eti 1) phenyl) phene lactic acid (0.05 g, 0.12 mmal), methanal acids (10 ml), and concentrated sulfuric acid (2 drops) or reflux for 1 hour in a 25 ml flask, and then quenched with a saturated solution of sodium bicarbonate, diluted with water (5 ml), was brought with ethylene chloride 3 x 5 ml), washed with brine (10 ml), dried (MgSO 4), and concentrated under reduced pressure. The residue was purified by flash chromatography (S? 02, 3: 1 / methylene chloride: methanol) which afforded 3- (3-alpha- , D-manop i anosi loxi et i 1) feni 1) feni lacetato (0.04 g, 77%); 1 H NMR: (300 MHz, DMSO-do) 7.2-7.6 (comp, 8H), 4.70 (s, 1H), 4.49-4.80 (comp, 7H), 3.75 (s, 2H), 3.62 (s, 3H) 3.30 -3.50 (comp, 5H) ppm; IR (KBr): 3383, 1738, 1135, 1066 cm-1. EXAMPLE 18 3- (3- (2-ALPHA-D-MANOP IRANOSI LOX IFENI L) FENI L) PROP I LF0SF0NAT0 OF ETHY Part A: A solution of 2- (3- (2- (2, 3: 4,6-d iQ- isoprap i 1 ideno) -af-D-manop ir nos i loxifenil) phenyl) et nal * (1.12 g, 2.46 mmol) in dichloromethane (15 ml) was slowly added to a suspension of Dess-Martin periadinan (4.95 g, 11.7 mmol) in dry dich larametan (5 ml), and the reaction was stirred at room temperature during the reaction. night. The mixture was then diluted with ether and filtered; the filtering was 15 washed twice with a solution saturated with sodium bicarbonate and once with brine, then dried with sulphate The magnesium was removed in vacuo and the residue purified by chromatography on silica gel (4: 1 hexane: ethyl acetate) to give 2- (2- (2,3: 4, or- di- 20 Q- i oprop i 1 ideno) -a 1 fa-D-manop iranosi loxyphenyl) phenyl tan (0.63 g 57%) Part B: Tetrae i lmet i lenedi phosphonate (0.37 g, 1.28 mmal) was dissolved in dry tetrahydrofuran (3.6 ml) under a blanket of nitrogen and the solution was cooled to minus 78 degrees C. 25 A 0.5 M solution was added dropwise. hexameti Id isi laz ida of potassium eptoluene (2.56 ml, 1.28 mmol), and the reaction was stirred for 10 minutes. A solution of 2- (2- (2,3: 4,6-di-Q-isoprap i 1 ideno) -al fa-D-manop i ranosi lo? I feni) feni letana 1 (0.58 g, 1.28 ml) in tetrahydrofuran (3.8 ml), and the reaction was allowed to warm to room temperature under stirring overnight. Water was then added and the mixture was extracted with ethyl acetate. The extracts were washed with water, 1 N HCl, a saturated solution of sodium bicarbonate, brine, and then dried over magnesium sulfate. The solvent was removed in vacuo and the residue was purified by chroma gel ography. silica (1: 2 hexane ethyl acetate) to give 3- (3- (2-a-lfa-D-manno-ranosi loxi-phenyl-1) phenyl) propyl-1-diethyl phosphonate (0.46 g, 63%). %). Part C: 3- (3- (2- (2, 3: 4, 6-d iQ-isopropy 1 ideno) -al fa-D-manop i ranosi lo? Ifeni l) feni 1) prop-l- was dissolved diethyl ether (0.46 g, 0.80 ml) in ethanol (25 ml) and hydrogenated (40 psi H2, 10% Pd / C) for 3 hours. The suspension was filtered through celite and the filtrate was concentrated under reduced pressure to provide 3- (3- (2- (2,3: 4,6-di-Q-isaprop i 1 ideno) -l fa-D- manap iranosi la? ifeni l) feni 1) propi 1 diethyl fasphonate (0.46 g, quantitative). , - > > Part D: 3- (3- (2- (2, 3: 4,6-d iQ-isapropi 1 ideno) - fa-D-manop i ranosi lo ifenil) phenyl) propylphosphonate diethyl (0.23) was dissolved g, 0.40 mmol) in methanol (2 ml). 2 N Hydrochloric acid (0.5 ml) was added and the reaction was stirred overnight. The solution was brought to a pH of 10 by the addition of 2 N NaOH and allowed to stir at room temperature for 3 hours. The reaction was heated at 60 degrees C for 18 hours, then at 80 degrees C for 116 hours. The solution was then cooled l- and acidified with 1N HCl, and the product was isolated by reverse phase HPLC preparation on a column of C18 Dynamax 300A 5 microns (21.4 x 250) at a flow rate of 10 ml / min. An elution gradient of 0-50% solvent B was used for 20 minutes, and solvent B is 15 composed of 95% acetyl triol / water, trichloracetic acid 0.1%, and solvent A was composed of 5% Ar "acetsni tri lo / water, trifluoroacetic acid 0.1%. The effluent was monitored at 254 nm, and the pure fractions were combined and lyophilized to provide (76.4 mg, 20 40%) of 3- (3- (2-alpha-D-mannopyrosi lo? I feni 1) feni 1) prapi 1 ethyl fasphonate in the form of a white solid, melting point: 67-70 degrees C; IR (KBr): 3404, 2931, 1478, 1454, 1423, 1222, 1108, 1043, 1008, 976, 797, 752, 706 cm-1; 1H NMR (300 MHz, D20): d 7.25 25 (, 8H), 5.41 (s, 1H), 3.88 (, 3H), 3.61 (m, 4H), 3.26 (m, rK, 1H), 2.64 (m, 2H), 3.78 (, 2H), 1.66I, 2H > , 1.16 (t, 3H J = 6.9). EXAMPLE 19 3- (2-ALPHA-D-MANOP IPANOS1 LOX IFENI L) FENI LACETONITRI LO 5 Part A: In a 50 ml bottle, 5.19 g (20.77 mmol) of 3-bramabenc bromide were dissolved? The residue was taken up in methanol (25 ml) and treated with a solution of sodium cyanide (1.29 g, 26.3 mmol) in water (5 ml) and the mixture was heated under reflux for 3 hours and then concentrated ba or reduced pressure. The residue was dissolved in full methylene chloride (20 l and washed with water (2.25 ml, saturated sodium chloride (25 ml), dried MgSO4) and then concentrated under reduced pressure which gave 4.01 g (98%) of 3- cyanomethylbenzene in the form of a light oil 15 Crude nitro in DME (10 ml) was added to a mixture of 2-h idraxibepcenboronic acid (2.9 g, 21 mmol), phosphate '"- tribasic potassium (13.4 g, 63 mmol) and b is (tp fem 1 phosphine) palad IO (II) chloride (0.3 g, 0.42 mmal) in DME (90 m) and the mixture was degassed. or nitrogen, after 20 heated or refluxed for 3 hours in a nitrogen atmosphere. The reaction was mixed with water (150 ml) and then the aqueous solution was brought to a pH of 4 with 2N HCl, then the mixture was extracted with ethyl acetate (3 x 15 ml). The organic materials were combined, dried 25 (MgSO 4) and then concentrated under reduced pressure which gave 3.8 g (89%) of 2- (3-cyanomethyl-1-pheni-1) phenol. An analytical sample was obtained by recrystallization from ethyl acetate, which yielded a white solid with a melting point of 113-114 degrees C. Part B: 2- (3-eianome i lfeni 1) phenol (0.5 g, 2.39 mmol) in 1, 2-d-chloroethane (10 ml) then p-fatacetate of al-D-mannose (1.4 g, 3.6 mmol) and boron trifluoride etherate (1.05 ml, 8.4 mmol) were added and The mixture was stirred at room temperature overnight and then mixed with water (20 ml). The organic material was separated, washed with saturated sodium chloride (15 ml), dried (MgSO 4) and then concentrated under reduced pressure. The residue was purified by flash chromatography (Si02, -3: 1 hexane / ethyl acetate) which gave 1.38 g (3.05%) of the desired product contaminated with a small amount of unreacted mannose pentaacetate which was coeluted with the product. Part C: 3- (2- (2,3,4,6-tetra-Q-acet i 1) -a 1 fa-D-anopyranosi lo? Ifeni 1) was dissolved phenylacetonyl tri (0.82 g, 1.52 mmol ) in THF (10 ml), then a solution of lithium hydroxide hydrochloride (0.5 g, 12.0 mmol) in water (2 ml) was added and the mixture was stirred at room temperature overnight and then concentrated under pressure. reduced. The residue was acidified to a pH of 4 with 2N HCl and purified by reverse phase HPLC (C18, elution of 0 to 50% gradient of acetonitoplo in water (0.1% TFA), monitored at 254 nm) which gave 202 mg (37%) of 3- (2- af -D-manop i ranosi loxif ni 3) feni lacetoni Ri lo in the form of a white solid, melting point: 70-72 degrees C. 1H NMR 5 (300 MHz, DMSO-do): 7.10-7.50 (comp, 8H), 5.38 (s, 3H), 4.02 (s) , 2H), 3.25-3.90 (comp). IR (KBr): 3424, 2934, 2258, 1477, 1425, 3220, 1109, 1009, 975, 756; Mass spectrum -Cl): m / e 372 μM + +1), 228, 115. Analysis: calculated for C39H21N06- .3 TFA: 61.00% C, 5.29% H, 3.45% N. Found:, 61.0% C, 5.53 % H, 3.49% N. EXAMPLE 20 ACID 2- 2'-ALFA-D-MAN0P IPANOSI LOX IFENI L i FEN0X IACETIC0 Part A: It was dissolved, 2'-d ihdrax ib i fepi la (lo g, 5.37 mmal) in THF (5 ml) in a dry 50 ml flask rinsed with nitrogen. Sodium hydride (0.24 g of a 60% suspension in mineral oil, 5.91 mmol) was added in one ^ portion and the mixture was stirred at room temperature or ba 30 minutes. Ethyl brsmoacetate (0.61 m3, 5.5 mmol) was added and the mixture was stirred overnight at room temperature, then heated under reflux for 30 minutes, cooled and then quenched with saturated ammonium chloride. The mixture was then extracted with ether, and the organic materials were combined, dried (MgSO 4) and then concentrated ba or reduced pressure. The residue was purified by flash chromatography (S? 02, elution / - - of gradient: hexane to 3: 1 hexane / ethyl acetate) which afforded 0.89 g (61%) of 2- (2'-idra? ifeni) ethyl phenoxyacetate. Part B: Distemically 2- (2'-hydroxy phenyl) phenoxyacetate (0.75 g, 2.75 mmol) in 3, 2-d? c-loroethane (10 ml) and then p -aceacetate of al-Fa-D-manssa (2.15 g, 5.51 mmol and boron trifluoride etherate (3.73 ml, 13. 8 mmol) were added, and the mixture was stirred at room temperature for overnight and then mixed with water (20 ml) The organic material was separated, washed with saturated sodium chloride (15 ml), dried (MgSO 4) and then concentrated under reduced pressure.The residue was purified by flash chromatography. (S? 02, 3: 1 hexane / ethyl acetate) which afforded 3.13 g (64%) of the desired product 5 contaminated with a small amount of unreacted pentaacetate of hands was co-eluted with the product Y- Part C: Dissolved 2- (2 '- (2,3,4,6-tet ra-Q-acet 11) -alpha-D- manop i ranosi 1-ox i feni l) phenoxy iaoetate (1.1 g, 1.84 mmal) in THF ( 10 ml) and then a solution of lithium hydroxide monohydrate (0.53 g, 32.6 mmol) in water (3 ml) was added and the mixture was stirred at room temperature overnight and then s concentrated ba or reduced pressure. The residue was acidified to a pH of 4 with 2N HCl and purified by reverse phase HPLC (C18 gradient elution from 0 to 50% acetonitoplo in water 0.1% TFA), monitored at 254 nm) which yielded 202 mg, (37%) of 2- (2'-al-fa-D-mannopyranosyl laxi-pheni-1) phenoxyacetic acid in the form of a solid white, melting point: 93-96 g. C. 1H NMR (300 MHz, DMSO-do): 2.85-7.35 (comp, 8H), 5.25 (s, 1H), 4.60 (s, 2H), 5 3.25-4.20 (comp, 11H). IR (KBr): 3417, 2934, 1735, 1481, 1443, 1215, 1107.1067, 978, 755. Mass spectrum (Cl): m / e 407 (M + +1), 245, 199, 115. Analysis: calculated for C20H2209.0.3 TFA, 0.3 H20: 55.70% C; 5.18% H. Found: 55.80% C, 5.47% H. V, EXAMPLE 23. ACI OR 3-f2-LF-D-MANOP IR NOSI LOX IFENIL) 5-METI L- FENQXI CETICO 3-bromo- -me was dissolved i 1 fenal (1.4 g, 7.5 mmol) in acetone (15 ml) in a dry 25 ml flask. "They added Ethyl bromoacetate (0.96 m, 8.66 mmol), then potassium carbonate (1.03 g, 7.5 mmol) and potassium iodide (25 mg) and f. The reaction mixture was stirred under reflux for one hour, then cooled and concentrated. The residue was mixed with water (15 ml) and ethyl acetate (10 ml). He Organic material was separated, then dried (MgSO4) and concentrated under reduced pressure. The residue was dissolved in hexane and filtered through silica gel and concentrated to provide 2.1 g (100%) of ethyl 3-bromo-4-ethoxyacetata which was used without any 25 additional purification. t and Part B: Degasi fi er 3-b bouquet-4-me 11 ethyl phenoxyacetate (0.5 g, 1.83 mmol), tetrakis tp pheny lphosf in) paladis (O) (37 mg), potassium phosphate (0.55 g) , 1.6 mmol) and give 11 for amide (8 ml) under nitrogen atmosphere in a 5 ml flask equipped with a reflux condenser. Acid-2-hydroxybenzoic acid (0.3 g, 2.0 mal) was added in dimethylformamide (1) and the mixture was heated under reflux overnight and then mixed with water (25 ml) ex. met full (3; - 3 ml). The organic materials were separated, dried, MgSO4 > and then concentrated under reduced pressure. The residue was purified by instantaneous chromatography SS 02 02, gradient of hexapa to 3: 1 hexane / ethyl acetate) which yielded 130 mg (25%) of 3- (2-hdrs i feni 1 i -4-5 met i 1 ethyl phenacetate, part C: 3- 2 2 -hydrox-lfeni 1) -a-methyl phenoxyacetata was dissolved Ethyl (130 mg, 0.454 mmol) in 1,2-d-chloroethane (2 ml) in a dry 10 ml flask. Alpha-D-anasa pentaacetate (0.4 g, 0.9 mmol) was added in one portion, then boron tetrachloride etherate (0.3 ml) was added slowly, 2.3 mmol). The mixture was stirred under a nitrogen atmosphere overnight at room temperature and then mixed with water (15 ml). The organic material was separated and the aqueous part was extracted with dich larametana (3 ml). The extracts were 5 combined with the original organic fraction, dried (MgSO4) and then concentrated under reductive pressure. The residue was purified by flash chromatography (Si02, hexane gradient elution to 3: 1 hexane / ethyl acetate) which yielded 0.42 g 0100%) of 3- (2- (2,3,4,6- 5 tetra-Q -acet i 1) -alpha-D-mannopi and loxyphenyl) -4- et i 1 ethyl phenaxyacetata contaminated by a small amount of al pentaacetate. unreacted fa-D-mannose that was co-eluted with the product. Part D: 3- (2- (2, 3, 4, o-tetra-Q-acet i.1) -a 1 fa-D- - _X > manop i ranosi loxi feni 1) -4- was dissolved met i 1 phenoxy iacetate (2.74 g, 4.78 M) enacetani tr i lo (10 ml), and treated with a solution of lithium hydroxide monohydrate (0.25 g, 5.95 mmol) in water (2 ml) and the The mixture was stirred at room temperature for 1-night and then acidified to a pH of 2. 15 with concentrated hydrochloric acid. The mixture was concentrated under reduced pressure and the residue was purified by HPLC (reverse phase, 5-50% gradient elution of acetonitrile in water, monitored at 254 nm) provided 101 mg (53% of 3- (2-hydrox i feni 1) -4-meth i phenoxyacetate of Ethyl) of 3- (3-al-Fa-D-manap i ranasi lax ifeni 1) -4- et i 1 phenoxyacetic acid, melting point: 87-89 degrees C. 1H NMR (300 MHz, DMSO-do ): 7.32 (s, 2H), 7.05-7.18 (comp, 3H), 6.80 (comp, 1H), 6.60 (br s, 1H), 5.31 (br s, 1H), 5.11 Cbr s, 1H), 4.9 ( br s, 1H), 4.60 (s, 2H), 4.59 (br s, 3.H), 3.10- 25 3.72 (camp, 7H), 2.00 (s, 3H). IR (KBr): 3424, 2931, 1735, .- 1484, 123.9, 13.93, 1068, 1010, 976, 757. Eespectro mass (Cl); m / e 421 (M + + 1), 259, 241, 213, 163, 145, 127, 115. Analysis: calculated for C21H2409.0.3 TFA: 57.07% C, 5.39% H. Found: 56.90% C, 5.57% H 5 EXAMPLE 22 ACID 3- (2-MET0XI-5- (3- (2-ALPHA-D-MAN0PIRAN0SIL0XYPENYL) -2- PHENYLACETHFEN0NA)) FE I LACET ICO Part A: 3- (2-meto? I feni) was dissolved l) methyl phenylacetate (0.82 g, 3.2 mmol) and 3-L, bromophene lactic acid chloride (0.77 g, 3.3 mmsl) in dichloroethane (11 ml) and cooled in an ice bath. Aluminum chloride (0.88 g, 6.6 mmol) was added in one portion and the mixture was heated at 50 degrees C for 15 minutes and then mixed with ice water (20 ml). The organic materials 15 were separated, dried (MgSO 4) and then concentrated under reduced pressure which afforded 1.68 g of 3- (2-methoxy-S ~ 5- (3-bromafeni 1-2-pheni lacetophenone)) methyl phenylacetate in the form of a yellow oil that was used without any additional purification. The crude halide was mixed with either 2-metho? I. Phenyl-1-boronic acid (0.54 g, 3.55 mmol) in toluene. (20 ml), then tetrakis were added (trifeni 1 phosphine) palladium (0) (120 mg, 3 mol%) and aqueous sodium carbonate (6 ml of a 2N solution) and the mixture was degassed under nitrogen. The mixture was then treated under reflux for 14 hours and then mixed with water (3.00 ml), and the mixture was extracted with ethyl acetate (3 x 8 ml). The organic materials were combined, washed with saturated sodium chloride (15 ml), dried (MgSO 4) and then reduced low pressure concentrates. The residue was purified by flash chromatography (Si02, hexane gradient elution to 3: 1 hexane / ethyl acetate) which yielded 1.57 g (77%) of 3- (2-methoxy-5- (3- (3- etax i feni 1) -2-feni lacetafenone)) feni lacet or methyl in the form of a clear acei e. t Part B: 3- (2-meto? i feni.1) -2-phenylacetafenone) methyl phenylacetata (0.68 g, 1.42 mmol) was dissolved in dichloromethane (5 ml.) under nitrogen, and cooled in a Dry ice bath / 2-propanal. Boron tribrosmide (0.8 ml, 8.5 mmol) was slowly added dropwise and the The mixture was kept at 0 degrees C for 1 hour, and then mixed with ice water (25 ml). The organic material was separated, washed with a saturated solution of sodium bicarbonate (10 ml), water (10 ml), saturated sodium chloride (10 ml) and then dried (MgSO4) and concentrated under pressure. 20, which gave 0.73 g of 3- (2-methoxy-5- (3- (2-hydroxy-phenyl) -2-phenylacetophenone)) methyl pheniacetate in the form of a clear oil. The crude phenol was dissolved in diclaroethane (10 ml) and alpha-D-mannose pentaacetate (1.8 g, 4.5 mmol) was added in one portion, and then added 25 slowly boron trichloride stearate (1.0 ml, 7.5 mmol). The mixture was stirred under nitrogen overnight at room temperature and then mixed with water (25 ml). The organic material was separated and the aqueous part was extracted with dichloromethane (3 x 2 ml). The extracts were combined with the original organic fraction, dried (MgSO 4) and then concentrated ba or reduced pressure. The residue was purified by flash chromatography (S? 02, hexane gradient elution to 3: 1 hexane / ethyl acetate) which afforded 0.8 g (73%) of 3- (2-metho? -5- (3- (2 - (2, 3, 4,6-0 gt ra-Q-ac 111) -a 1 f -Dm nop i rano i lox i fen 11) -2- feni lacetafenon)) methyl phenylacetate contaminated with a dry amount of unreacted α 1 fa-D-mannose pentaacetate that was co-eluted with the product. Part. C: 3- (2-methox? -5- (3- (2- (2, 3, 4, 6-tetra-Q-5 acetyl) -alpha-D-manop i raposi loxi feni was dissolved ) -2- feni lacetafenone)) phenylacetate methyl (0.8 g, 1.0 mmol) - "in tetrahydrofuran (6 ml), and treated with anhydrous lithium hydroxide solution (0.25 g, 6.0 mmol) in water of 3 ml.) The mixture was stirred at room temperature overnight and then acidified to a pH of 2 with concentrated hydrochloric acid and concentrated under reduced pressure, the residue was purified by reverse phase HPLC, gradient elution 5-50% of acetanitide in water, monitored at 254 nm) 134 mg (22%) was provided. of Acid 5 3- (2-meto: <? -5- i3- (2-al fa-D-manap i ranosi loxifeni 1) -2- feni lacetophenone)) fepi lacet ico in the form of a white solid, melting point: 122-125 degrees C. 1 H NMR: (300 MHz, DMS0-do); 8.13 (dd, J = 8.8, 2.2 Hz, 2H), 7.95 (d, J = 2.2 Hz, 1H), 7.22-7.43 (camp, 12H) 7.09 (mu.lt, 1H), 5.34 (d, J = 1.5 Hz, 1H), 4.44 (dd, J = 19, 15.8 Hz, lH) m 4.16 (br s, 4H), 3.85 (s, 3H), 3.70 (comp, 1H), 3.62 (s, 2H), 3.34 -3.55 (comp, 3H), 2.07 (s, 2H). IR (KBr): 3415, 1713, 1Ó9, 1597, 1269, 1217, 1135, 1015. Mass spectrum (Cl): m / e 453 < M + minus C6H1105). < EXAMPLE 23 ACID 3-l2-ALPHA-D-MAN0PIRAN0SIL0XYPENYL-5- (2-y3- (2-ALPHA-D- AN0P IRANOSI LO IFENI L) FAITH IL) ETI L)) PHENY LACETICO Part A: Dissolved 3 - (2-meto? I-5- (3- <2-methoxy-feni-1) -2-feni-lacetophenan)) methyl-phenylacetate (2.25 g, 4.68 mmol) in DMSO (15 ml) and the solution was treated with aqueous potassium hydroxide (2.5 ml of a 2 N solution) and then stirred at 60 degrees C under nitrogen atmosphere for one hour. The mixture was cooled to room temperature and treated with hydrazine hydrate (0.4 ml, 11.7 mmol), and then heated at 60 degrees C for an additional hour. Potassium tert-butoxide (1.31 g, 11.7 mmol) was added and the temperature was increased to 100 degrees C. After 18 hours, the mixture was cooled, mixed with water (50 ml) and acidified to a pH of 4. with 2 N HCl. The mixture was saturated with sodium chloride and brought with THF / ethyl acetate. -, (1: 1) and the extracts were combined, dried (MgSO 4) and then concentrated under reduced pressure which gave 2.29 g of a dark oil. The crude product was dissolved in dichloromethane (25 ml) and cooled in a dry ice / 2-propanal bath. Boron tribromide (2.4 ml, 25 mmol) was added dropwise and the mixture was stirred at -78 degrees C for 2 hours, heated to 0 degrees C for 2 hours and then cooled again to -78 degrees C for shutdown with water. The mixture was concentrated under reduced pressure and the < The residue was divided between THF and saturated sodium chloride. The organic material was separated, dried (MgSQ4) and then concentrated. The residue (2.63 g) was dissolved in methanol (30 ml) and 5 drops of concentrated sulfuric acid were added and the mixture was refluxed overnight and then concentrated. The residue was purified by flash chromatography (Si02, gradient hexane elution , / 3: 1 hexane / ethyl acetate) which yielded 0.89 g (43%) of 3- (2-h id rox i phen i 1-5- < 2- (3- (2- h idrox i feni 1) feni 1) et i 1)) methyl phenylacetate in the form of a clear oil. Part B: 3- (2-Hydraxy-phenyl-1-5- (2- (3- (2-hydrox-ifeni-1) -phen-1) -eti (1)) phenylacetata methyl (0.69 g, 1.57 mol) was dissolved in dichloroethane ( 3.0 ml) and alpha-D-mannose pentaacetate (1.8 g, 4.5 mmol), added in one portion, and then boron trifluoride etherate was slowly added. (2.3 ml, 18.8 mmol). The mixture was stirred under nitrogen overnight at room temperature and then mixed with water (50 ml). The organic material was separated and the aqueous part was extracted with dichlarsmethane (3 x 2 ml). The 5 extracts were combined with an original organic fraction, dried (MgSO 4) and then concentrated under reduced pressure. The residue was purified by flash chromatography (Si02, hexane gradient elution at 3: 3, hexane / ethyl acetate) which yielded 1.38 g (66%) :; .. > of 3- (2'2,3,4, o-tetra-Q-acetyl) -alpha-D-m not ir nosi lox i feni 1) -5- (2- (3- (2- (2, 3 , 4, 6-tetra-Q-acet 11) - a 1 fa-D-manop) i ranosi lox i feni 1) feni 1) et i 1)) phenylacetamide in the form of foam. The product was dissolved in acetonitrile (5 ml) and treated with a hydrate solution of 15 lithium hydroxide (0.24 g, 5.6 mmol in 5 ml of water) and stirred at room temperature overnight, and then acidified to a pH of 3 with concentrated HCl and concentrated under reduced pressure. The residue was purified by reverse phase HPLC (C18, elution gradient from 0 to 50% acetanitrile in water (0.1% TFA), monitored at 254 nm) which yielded 142 mg (18%) of acid 3 - (2-alpha-D-hand iranosi laxi feni 1) -5- (2- (3- (2-a 1-fa-D-mannopyranasi la? Ifeni 1) feni 1) et il)) lactic phenol in form of a white solid, melting point: 129-134 degrees C. 1H NMR: 5 (400 MHz, DMS0-do>: 7.3.0 -7.40 (comp, 15H), 5.33 (d, J = 1.7 A Hz, 1H), 5.27 (d, J = 1.7 Hz, ÍH), 3.30-3.70 (comp, 14H, plus H20), 2.92 (2, 4H). IR (KBr): 3410, 2935, 1710, 1478, 1222, 1113, 1064, 1011, 977 .. Mass spectrum (Cl): m / e 425 (M + minus C12H20010). Analysis: calculated for C40H44014, 2.2 5 H20: 60.94% C, 6.19% H. Found: 60.70% C, 5.84% H. EXAMPLE 24 ACID 2,6-DIMETHYL-4- (2-ALPHA-D- MAN0P IRAN0SI LOX IFE IL) IACTIC FENOX, Part A: 4-bromo-2,6-d imet i 1 phenol (8.0 g, 39.8 0 mM) was dissolved in toluene (80 i) in a phrasing of 25 C * ml. Potassium bis (trimethylsilyl) amide (80 ml, 39.8 M) was added and then tris (2- (2-methox i or i) et i 1) amine (1.3 ml, 4.0 mM), and stirred under nitrogen for 45 minutes. Ethyl bromadiacetate (5 ml, 43.8 mM) was added, and it was stirred at room temperature overnight. The reaction mixture was mixed with a saturated solution of ammonium chloride (30 ml), and extracted with ethyl acetate (3 x 50 ml). The organic materials were combined, dried (MgSO4), and concentrated under reduced pressure. The residue 0 was passed through silica gel with hexane / ethyl acetate (10: 1) and concentrated, which provided 11.3 g (99%), of 4-bromo-2,6-dimethylphen-ioacetate. 1H NMR: (400 MHz, CDC13): 7.13 (s, 2H), 4.35 (s, 2H), 4.26-4.31 (q, 2H), 2.25 (s, OH), 1.23-1.33 (t, 3H) ppm. IR (NaCl): 2987, 1749, 5 1470, 1287, 1192 cm-1.

Part B: 2-hydroxybenzeneboronic acid (2.0 g, 14.5 mM), ethyl 4-bromo-2,6-dimethexenoacetate (4.2 g, 14.5 mM), tribasic potassium phosphate (7.7 g, 36.3 mM), and DME (30 ml) were degassed under nitrogen in a 100 ml flask equipped with a reflux condenser. Bis (triphenylphosphine) palladium (II) chloride (0.20 g, 0.3 mM) was added. The mixture was degassed under nitrogen and heated at 80 ° C overnight, and then mixed with brine (20 ml), and extracted with ethyl acetate (3 x 20 ml). The materials X > organic, dried (MgSO4), and then concentrated under reduced pressure. The residue was purified by flash chromatography (Si02, 10: 1 / hexane: ethyl acetate) which yielded 1.08 g (23%) of 2,6-dimet i 1-4- (2- h idrox i feni 1) phenoxyacetate of ethyl. 1H NMR (500 MHz, 15 CDC13): 7.21-7.29 (comp, 6H), 4.48 < s, 2H), 4.32-4.37 (q, 2H), 2.38 (s, OH), 1.35-1.39 (t, 3H) ppm. IR (NaCl): 3438, /, 1738, 1484, 1443, 1203, 1176, 1080 cm-1. Part C: 2,6-dimeti 1-4- (2-h idrofeni 1) ethyl acetate (1.08 g, 3.6 mM) in 1,2-dichloroethane (10 ml) was dissolved in a 20 dry bottle of 50 ml. Alpha-D-anose pentaacetate (1.75 g, 4.5 M) was added in one portion, and then boron trifluoride etherate (1.3 ml, 10.8 mM) was added slowly. The mixture was stirred under nitrogen overnight at room temperature, and then mixed with water (30 ml). He 25 organic material and the aqueous part was extracted with dichloromethane (3 x 10 ml). The extracts were combined with the original organic fraction, dried (MgSO4), and then concentrated under reduced pressure. The residue was purified by flash chromatography (Si02, 10: 1 / hexane: ethyl acetate) which gave 2.4 g (95%) of 2,6-d imet i 1-4- (2- (2, 3, 4, 6-tetra-Q-acet i 1) -a 1 fa-D-anop i ranosi loxifeni 1) ethyl phenaxyacetate contaminated with a small amount of unreacted a-pentaacetate from a 1 fa-D-manase which dried eluted with the product. 1H NMR (500 MHz, r.CDC13): 7.13.-7-35 (comp, OH), 5.42 (s, 1H), 4.47 (s, 2H), 4.29-4.34 (comp, 2H), 2.36 (s, 6h), 2.17-2.18 (comp, 6H), 1.97-2.14 (7H), 1.32-1.35 (comp, 3H) ppm. IR (NaCl): 2972, 1752, 1471, 1436, 1375, 1210, 1176, 1142, 1080, 1032, 970 cm-1. Part D: 2,6-d imet i 1-4- (2- (2,3,6,6-tetra-O-acet i 1) -alfa-D-mapopi ranasi lo? I feni 1 was dissolved ethyl phepaxyacetate r > (2.4 g, 3.8 M) in acetonitrile (10 ml) in a 50 ml flask, and treated with a solution of onah idrata lithium hydroxide (1.5 g, 38.0 M) in water (20 ml), and the mixture It was stirred at room temperature overnight. The acetonitrile was evaporated under reduced pressure. The residue was acidified to a pH of 2 with concentrated hydrochloric acid, and then purified by HPLC (reverse phase), gradient elution 10-60% acetynil in water, monitored at 254 nm) which yielded 0.88 g (53%) of acid 2, 6-d ime i 1-4- t? (2- lf -D-mannopyran i loxifeni 1) pheno? iacét ico, melting point, 95-96ßC. 1 H NMR (300 MHz, DMSO-do): 7.06-7.31 (comp. 6H), 5.29 (s, 1H), 4.40 (s, 2H), 3.28-3.68 (comp, 10H plus water), 2.25 (s, 6H) ppm. 5 Analysis: calculated for C22H2609.0.27 TFA: 58.19% C, 5.69% H. Found: 58.15% C, 5.98% H. EXAMPLE 25 ACID 2, o-DIMETHYL-4- (3-ALPHA-D-MAN0PIRAN0SIL0XIMETILFENIL) FEN0XIACETIC0, 1.- Part A: Operates the same as in Part B in the EXAMPLE 21, but by the use of 3- hydro acid? i et i Ibencenborónico obtained 2,6-dimet i 1-4- (3 - hydrax imet i 1 feni 1) phenoxiethe ethyl acetate with a yield of 30%. 15 Part B: Operated in the same manner as in Part C in the EXAMPLE 21, but using 2,6-dimet i 1-4- (3 -: - > - hydrox imeti lphenyl) pheno? Et i lacetatose obtained 2,6-dimet il-4- (3- (2,3, 4,6-tetra-Q-acet i 1) -alpha-fa-D-mannopi ranosi loxybenzyl) phenoacetic acid with a yield of 118%. The desired product was contaminated with a small amount of unreacted pentaacetate from the f-D-mannose that was eluted with the product. Part C: It was operated in the same way as in part D in the EXAMPLE 21, but by the use of 2,6-dimet i 1-4- (3-25 (2,3,4, o-tet aQ-acet i 1) -lf -D-manopiranasi lo? I et i 1 feni 1) A- ethyl phenoxyacetate was obtained with 2, 6, dimet i la-4- (3- a fa-D-manap iranosi lo? Ifeni 1) phenaxeacetic acid with a yield of 25%, melting point: 131-132 ° C. 1H NMR (300 MHz, DMS0-d6): 7.29-7.55 (comp, 6H), 4.50-4.76 (comp, 7H), 4.40 (s, 1H), 3.40-3.65 (comp, 7H), 2.30 (s, 6H) ) ppm. IR (KBr): 3397, 2924, 1752, 1710, 1477, 1443, 1203, 1135, 1066 cm-1. Analysis: calculated for C23H2809.0.3 TFA: 58.73% C, 5.91% "_ H. Found: 58.66% C, 6.22% H. EXAMPLE 26 Ac gone 3- i 3-a 1 fa-D-manap i ranosi lox ibenci 1 ) iacét ico faith. Part A: 3-Bromophenol (9.0 g, 52.0 M) was dissolved in DMF (105 ml) in a 250 ml flask. Sodium hydride (2.3 g, 57.2 mM, 60% dispersion in mineral oil) was added and stirred under a nitrogen for one hour. Ethyl bromoacetate (6.35 ml, 57.2 mM) was added and stirred And room temperature during the night. Water (800 ml) was added slowly under stirring in an ice bath. The formed precipitate was filtered and 11.9 g (88%) of ethyl 3-bromophenoxyethyl acetate was obtained. Part B: Ethyl 3-bramafenaxyacetate (1.7 g, 6.6 mM), bis (tri-phenyl-1-phosphono) palladium (II) chloride were degassed. (0.09 g, 0.13 mM), tribasic potassium phosphate (4.2 g, 19.7 M) and DME (30 ml) under nitrogen in a 100 ml flask equipped with a reflux condenser. Acid 3- was added The hydroxybenzene (0.8 g, 5.3 mM) in DME (1 ml) was added and the mixture was heated to 80 * C overnight, and then mixed with brine (20 ml), and extracted with ethyl acetate (3 x 20 ml). The organic materials were combined, dried (MgSO4), and then concentrated under reduced pressure. The residue was purified by flash chromatography (Si02, 10: 1 / hexane: ethyl acetate) which afforded 0.28 g (19%) of ethyl 3- (h idrox imeti 1 pheny1) phenoxyacetate. \ \) Part C: Packed in the same way as in Part C in the EXAMPLE 1, but by using ethyl 3- (3-h idrox i et i 1 phenyl) phenoxyacetate, 3- (3- (2, 3, 4, or-tetra-Q-acet i 1) -a was obtained. 1 fa-D-manop i ranosi l-oxybenzyl 1) ethyl phenoxyacetate with a yield of 45%. 15 Part D: Operated in the same manner as in Part D in EXAMPLE i, but by using 3- (3- (2,3,4,6-tetra-Q-> g "acet i 1 ) -al fa-D-manopi ranosi loxibenci 1) ethyl phenoxyacetate was obtained 3- (3-al fa-D-man-p i ranosi loxibenci 1) ethyl phenoxyethyl acid as a yield of 35%, from 20 fusion: 73-75ßC. 1H NMR (300 MHz, DMSO-do): o.90-7.60 (comp, 8H), 4.72 (comp.sub.4H>, 4.51 (d, 1H), 3.50-3.66 (comp, 10H plus water) ppm. (KBr): 3431, 2931, 1738, 1608, 1423, 1210, 1066 cm-1 Analysis: calculated for C21H2409.0.25 TFA: 57.52% C, 5.44% 25 H. Found: 57.29% C, 5.58% H: EXAMPLE 27 Ac gone 4- (3-al fa-D-manop i ranosi loxibenci 1) pheno? iacé ico. Part A: Operated in the same manner as in Part A in EXAMPLE 26, but by the use of 4-bramaphenol ethyl 4-bromophene acetate was obtained in 100% yield. Part B: Operated in the same manner as in part B in EXAMPLE 26, but by the use of ethyl 4-bromophenoxyacet to obtain ethyl 4- (3-h idrox imet i 1 pheny1) phenacetaceta with a yield of 26%. Part C: Operated in the same way as in Part C in the EXAMPLE 21, but by the use of 4- (3-h idrox ie 11 phenyl) phenamethyl acetate there was obtained 4- (3- (2,3,4,6-tetra-Q-acet i 1) -alpha. -D-hand i ranosi lo? Ibenc i 1) phenoxyacetic with a yield of 33%. Part D: Operated in the same manner as in Part D in EXAMPLE 21, but by using 4- (3- (2,3,4,6-t tra-Q-acet i 1) -al acid fa-D-manopi ranosi lox.ibenc i 1) phenoxy phenoxy acid was obtained 4- (3-al fa-D-mano-p i ranosi loxibenci 1) phenoxyacetic with a yield of 57%, melting point L 83- 85 ßC. 1H NMR (300 MHz, DMSO-do): o.98-7.60 (comp, 8H), 4.46-4.77) comp.8H), 3.37-4.2 (comp, 7H), IR (KBr): 3424, 2931, 1738 , 1608, 1512, 1436, 1224, 1073 cm-1. Analysis: calculated for C21H2409.0.2 TFA: 57.99% C, 5.50% H. Found: 57.98% C, 5.72% H.

~ EXAMPLE 28 3- (3-alpha-D-Manno-irano-i-lo-ibenc-1) benzoic acid. Part A: 3-Hydra? Imeti-l-benzeneboronic acid (2.0 g, 13.2 mM), 3-bromobenzoic acid (2.1 g, 10.5 mM), 5-tribasic potassium phosphate (8.3 g, 39.5 mM), DMF (26 ml) were degassed. and water (20 ml) under nitrogen in a 100 ml flask equipped with a reflux condenser. Bis (triphenylphosphino) palladium (II) chloride (0.18 g, 0.26 M) was added. The mixture was degassed with nitrogen and heated to 90 ° C overnight, then acidified with HC12N, mixed with brine (15 ml) and extracted with ethylene chloride (3 x 15 ml). The organic materials were combined, dried (MgSQ4), and then concentrated under reduced pressure which afforded 1.57 g (52%) of 3- (3-hydro? Imet i 1 phenyl) -5-benzoic acid. Part B: It was operated in the same way as in Part C in EXAMPLE 21, but by using 3- (3-hydro-imethyl phenyl) benzoic acid, 3- (3- (2,3,4) acid was obtained , 6-tetra-Q-aceti 1) -alf -D-mano i ranasi lo? Ibenci 1) benzoic with 0 a yield of 53%. Part C: Operated in the same manner as in Part D in EXAMPLE 21, but by the addition of 3- (3- (2,3,4,6-tetra-Q-acet i 1) -al fa-D-manap i ranasi lo? ibenci 1) benzoic acid was obtained 3- (3-al fa-D-mannopyranosi lo? ibenci 1) benzoic 5 with a yield of 29%, melting point: 90-91'C . 1H NMR , -_ (300 MHz, DMSO-do): 7.38-8.3.8 (comp, 8H), 4.72-4.77 (co p, 2H), 4.51-4.55 (d, 1H), 3.40-3.71 (comp, 10H plus water) ppm. IR (KBr): 3424, 2931, 1704, 3.409, 1244, 1128, 1059 cm-1. Analysis: calculated for C20H2208, 0.24 TFA: 58.88% C, 5.37% 5 H. Found: 58.85% C, 5.66% HEJEMPLO 29 Acid 3- (2-al fa-D-mannopyranasi lo? I-5-ethylphepil >Benzoxyacetic Part A: 2-bromo-4-meth i 1 phenol (2.60 ml, 21.51 0 'nmol in anhydrous diethyl ether (20 ml) was dissolved and the solution was cooled to minus 78 ° C. A solution of n-butylithium was added. in hexane (19.0 ml, 47.5 mmol slowly and the reaction was stirred for 10 minutes at a temperature of minus 78 ° C, and then for one hour at room temperature.) Bottle 5 was cooled to 0 ° C, and then trimet was added. iborate (2.44 ml, 10.73 mmol), followed by anhydrous THF (10 ml) The reaction was stirred at room temperature for 2 hours, then carefully quenched with water, the aqueous layer was acidified, and the stirring continued. for 30 minutes The mixture was extracted with ether and the organic phase was washed with a saturated solution of sodium chloride, and then dried with magnesium sulfate and concentrated under reduced pressure. The resulting coffee residue was triturated with hexane and filtered to provide 2-hydroxy-5- acid. r -methylbenzeneboronic acid (1.35 g, 8.9 mmol, 41%) as a white solid. Part B: 2-Hydro-i-5- et i-benzenebaronic acid (1.17g, 7.70 mmol) and ethyl 3-bromaphene-iacetate (1.99m, 7.68 mmol) were dissolved in dimethoxyethane (30 mL). The solution was completely degassed and then a catalytic amount of bis (tri-phi-1-phosphino) palladium (II) chloride was added. The reaction mixture was degassed again and then subjected to refluxing overnight under nitrogen. Ethyl acetate and dilute HCl were added and the organic phase was washed with water and then with a saturated solution of sodium chloride, and dried with magnesium sulfate and then concentrated in vacuo. The resulting residue was chromatographed on silica gel (3: 1 hexane: ethyl acetate) to provide ethyl 3- (2-hydrsxy-5-methyl-1-pheny1) phenoxyacetate (1.25 g, 4.37 mmol, 57%) in the form of a yellow oil. Part C: Ethyl 3- (2-h idro? I-5-methyl-1-pheny1) benzoxyacetate (0.30 g, 1.05 mmol) and al-fa-D-mannose penta acetate (0.45 g, 1.15 mmol) were dissolved. ) in anhydrous 1,2-dichloroethane (4 ml). Boron trifluoride diet and leterate (0.52 ml, 4.21 mmol) was added and the mixture was stirred at room temperature overnight. The reaction was carefully quenched with water, and then extracted with dichloromethane. The organic phase was dried with sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (2: 1 hexane: ethyl acetate) to provide 3- (2- (2,3,4,6-tetraacetyl-1-fa-5 D-mannopyranosyl loxy) -4-methyl-1-pheni-1) ethyl-phenacetic acid (0.40 g, 0.65 mmol, 62%) as a colorless glass. Part D: 3- (2- (2,3,4,6-Tetraacet i 1 -alpha-D-manap i rapasi was dissolved in ethyl) (-39) -4-meth i 1 pheny1) phenoxyacetats g, 0.63 mmol) in methanol (3 ml), and a solution of. 2 N sodium hydroxide (1.70 ml). The reaction was stirred for 30 minutes, and then the solution was acidified with 1 N hydrochloric acid, concentrated in vacuo, and microfilled. The product was isolated by half reverse phase HPLC of preparation on a C18 Dyna ax 300 5 () 5 column (23.times.250 mm). A gradient of 10-70% solvent B was used for 20 minutes at a flow rate of 10 / * - ml / min, where solvent B was composed of 95% acetani tri la / 0.1% TFA and solvent A was composed of 5% acetoni tri lo / 0.1% TFA. The effluent was onitored 0 to 254 nm, and the pure fractions were combined and mixed to give 173.3 mg (60%) of 3- (2- to fa-D-manop iranosi lo? I-4-meti lfeni 1) feno? iacétíco in the form of a white solid, melting point: 83-84ßC. NMR (do- DMS0): d 7.31 (t, 1H, J = 8.0), 7.21 (d, 1H, J = 8.1), 7.10 5 (m, 3H), 6.95 (s, 1H), 6.87 (d, 2H , J = 8.1), 5.22 (s, 1H), n: 4. 70 (s, 2H), 3.66 (s, 1H), 3.57 (d, 1H, J = 11.4), 3.44 (, 3H), 3.33 (, 1H), 2.29 (s, 3H). IR (KBr): 3417, 2931, 1731, 1215, 1177, 1066, 1011 cm-1. MS (Cl): m / z = 259. Analysis: calculated for, C21H2409, 1/4 CF3C02H, 57.5% C, 5.4% H; 5 found: 57.7% C, 5.5% H. 1 0 fifteen X- twenty 25

Claims (1)

1. CLAIMS 1. A compound that has the formula where X is selected from the group consisting of -CN, - (CH2) nC02H, -0 (CH2) mC02H, - < CH2) nC0Z, - (CH2) pZ, CHC02H (CH2) mC02H, - (CH2) nO (CH2) mC02H, -CONH (CH2) mC02H, -CONH 15 (CH2) mC02H, -CH (OZ) (C02H), -CH (Z) (C02H), - (CH2) nS03H, - (CH2) nP03DlD2, -NH (CH2) C02H, -CONH (CHR6) C02H, (1-H- '- "- tetrazole and 1-5-alky1-), and -OH; R1 and R2 are independently selected from the group consisting of hydrogen, alkyl, halogen, -OZ, -N02, - (CH2) nC02H, - H2 and NHZ; R3 is selected from the group consisting of hydrogen, halogen, alkyl, OZ and -NHZ; R4 is selected from the group consisting of hydrogen, halogen, alkylaryl, hydroxyl , h idro? i-0-sulfate and -OZ; P.5 is selected within the group consisting of hydrophilic, -CN, -N3, -NH2, -NHNH2, -NE1E2, -NHE1, -NHCO (CH2) nC02H, -S (CH2) mC02H and -NHCHNHNH2; and R6 is selected from the group consisting of hydrogen, Alkyl, aralkyl, hydroalkyl, aminoalkyl, alkylcarboxylic acid and alkylcarbamide; where n is 0 to 6, m is 1 to 0, p is 0 to 6, b is 0 to 2, Z is alkyl, aryl or aralkyl, The is alkyl or - (CH2) aC02H where a is 1 to 18, and E2 is alkyl, and the salts, esters, Xs 1 'amides and pharmaceutically acceptable prodrugs of the io. 2. The compound of claim 1 wherein 'Z is -CH2C02H; R1, R2 and R3 are hydrogen; R4 is -OH; R5 is - SCH2C02H; n and p are 1; b is 0; and the manspiresoside portion joins the P.3 that 15 contains the phenyl ring in the ortho position. 3. The compound of claim 1, wherein X is -CH2C02H; ^ --- Rl, R2 and R3 are hydrogen; R4 is -OH; R5 is - SCH2C02H; n and p are 1; b is 0; and the ansp iranoside moiety is bound in the R 3 containing the phenyl ring in the ortho position. 4. The compound of the rei indication 1, where X is -CH2C02H; R1, R2 and R3 are hydrogen; R4 and R5 are OH; n, p and b are 1; and the anopyranoside moiety binds to the R 3 containing the phenyl ring in the meta position. 5. The compound of the rei indication 1, where each The alkyl substituent is lower alkyl. 6. The compound of claim 1, wherein X is // CHC02HCH2C02H; R1, R2 and R3 are hydrogen; R4 is -OH; and R5 OH. 7. A compound that has the formula: where X is -Q, (CH2) nQ, -0 (CH2) nQ, - (CH2) nO (CH2) mQ, C0NH (CH2) nQ, -NH (CH) mQ, - (CH2) nQ (CH2) mQ , -CONH (CH2) nq; R1 and R2 are independently selected from the group consisting of hydrogen and - (CH2) nQ; j R4 is hydrogen or hydrogen; R.6 is selected from the group consisting of hydrogen, alkyl, aralkyl, hydroxyalkyl, aminoalkyl, alkylcarbamate, and alkylcarbamide, Q is -C02H, n is O to 6, and m is 1 to 6, and pharmaceutically acceptable salts, esters, and amides. 8. The compound of claim 7, wherein X is -CH2C02H and R4 is -OH. 9. The compound of claim 7, wherein X is -CH2H and R4 is -OH. 13. 6 - ^ 10. The compound of the rei indication 7, where X is - CH20CH2C02H and R4 is -OH. 11. The compound of claim 7, dapde X is -C0NHCH2C02H and R4 is -OH. 12. The compound of claim 7, wherein X is -0CH2C02H and R4 is -OH. 13. The compound of claim 7, wherein X is -C0NHCHIC02H) (CH2C6H5) and R4 is -OH. 14. The compound of claim 7, wherein X is - CONHCHIC02H) (CH2CH2CQ2H) and R4 is -OH. 15. The compound of claim 7, wherein X is -C02LÍ and P.4 is -OH. 16. The compound of rei v ind ica tion 7, where X is - (CH2) 2S03H and R4 is -OH. 17. The compound of the rei indication 7, where X is - C0NHCH2CH2C02H and R4 is -OH. - ^ 18. The compounds of the formula IV: where X is selected from the group consisting of -CN, - (CH2) nC02H, -O (CH2) mC02H, -CH2) nC0Z, - (CH2) nZ, eleven' CHC02H (CH2) mC02H, - (CH2) nO (CH2) mC02H, -CONH (CH2) mC02H, - CH (OZ) (C02H), -CH (Z> (C02H), - (CH2) mS02H, - ( CH2) nP03D! D2, - NH (CH2) mC02H, -CONH (CHRÓ) C02H, (1-H-tet r zal i 1-5-a l-1-), and -OH; 5 where W is hydrogen, alkyl or lfa-D-manosi lo and Y is selected from H / H, oxygen, H / hydroxyl, H / NH2, H / NHE1, H / NE1E2, NH, NE, NE1, oxime and 0-lqui lo? im, and the pharmaceutically acceptable salts, esters, amides and prodrugs thereof; wherein: n is from 0 to 6, m is from 3 to 6, p is 0 to 6, b is 0 to 2, Z is alkyl, aryl or aralkyl, DI and D2 are independently hydrogen or alkyl, E is alkyl or - (CH2) aC02H where a is l to 18, and E2 is alkyl and pharmaceutically acceptable salts, esters, amides and prodrugs 15 of them; each of R1 and R2 is independently selected within, -,., from the group consisting of hydrogen, alkyl, halogen, -OZ, -N02, - (CH2) nC02H, -NH2 and -NHZ; R3 is selected from the group consisting of hydrogen, halogen, alkyl, -OZ and -NHZ; R4 is selected within the crane consisting of hydrogen, halogen, alkyl, hydroxyl, hydraxy 1-0-sulfate and -OZ; R5 is selected from the group consisting of hydroxyl, -CN, -N3, -NH2, -NHNH2, -NE1E2, -NHE1, -NHCO (CH2) nC02H, -5S (CH2) mC02H and -NHCHNHNH2; Y R6 is selected from the group consisting of hydrogen, alkyl, aralkyl, hydrayalkyl, aminoalkyl, alkylcarboxylic acid and alkylcarboxamid. 19. The compound of claim 18, wherein X is CH2C02H; each b is 0; each Rl, R2 and P.3 is H; R4 and R5 is OH and p is 1. The compound of claim 19, wherein W is alpha-D-anasyla and Y is H / H. 21. The compound of the rei indication 19 where it is methyl and Y is oxygen. 22. A method for inhibiting the binding of E-selectin, and / or P-selectin and / or L-selectin on sial i-Lewis (x) or sialyl-Le? Is (a) presented on a cell surface comprising the step of administering to an animal that requires such treatment an effective amount of inhibition of at least one compound having the formula: , where X is selected within the group consisting of -CH, - (CH2) nC02H, -0 (CH2) mC02H, - (CH2) nO (CH2) mC02H, - (CH2) nC0Z, - (CH2) nZ, -CHC02H (CH2) mC02H, -CONH (CH2) mC02H, - CH < 0Z) (C02H), -CH (Z) (C02H), - (CH2) nS03H, - (CH2) nP03DlD2, -NH (CH2) mC02H, - C0NH (CHR6) C02H, and (1-H-tetrazole i 1 -5-a lqui lo-), and -OH; R1 and R2 are independently selected within the group consisting of hydrogen, alkyl, halogen, -OZ and -NHZ; P.4 is selected from the group consisting of hydrogen, halogen, alkyl, hydroxyl, hydroxyl, 1-0-sulfate and -OZ; A P5 is selected from the group consisting of hydrogen, hydroxyl, -CN, -N3, -NH2, -NHNH2, -NE1E2, -NHE1, -NHC0 (CH2) nC02H, -S (CH2) mC02H and -NHCHNHNH2; and R6 is selected from the group consisting of hydrogen, alkyl, aralkyl, hydroalkylalkyl, aminoalkyl, alkylcarboxylic acid and alkylcarbamide; where n is from 0 to 6, m is from 1 to 6, p is 0 to 6, b is 0 to 2, ^ 2 is alkyl, aryl or aralkyl, DI and D2 are independently hydrogen or alkyl, He is alkyl or - (CH2) 8C02H, and E2 is alkyl, and pharmaceutically acceptable salts, steres, and amides. 23. A pharmaceutically active composition comprising a compound of the rei indication 1 and a pharmaceutically acceptable carrier. 24. A method for the treatment of any of the selected diseases within the group consisting of septic shock, chronic inflammatory disease, psoriasis, rheumatoid arthritis, reperfusion damage that occurs after heart attacks, strokes, and organ transplants, traumatic shock, organ failure 5 multiple, autoimmune diseases, asthma, inflammatory bowel disease, Crahn syndrome, ARDS and cancer, which comprises administering to a patient suffering from any of these diseases a therapeutically effective amount of the compound of claim 1 or reduce the symptoms of the disease. fifteen twenty 7ei