WO2005019236A1 - Novel sulfenamide oxides - Google Patents

Abstract

Sulfenamide oxide compounds of general formula (I) are disclosed wherein A, R1, R2, X1, X1’, X2, X2’, X3, X3’, X4, X4’, X5 and X5’ define a variety of variables and wherein q is 0 or 1 and p is 1 or 2. The compounds disclosed in the examples are galactofuranosyl and glucofuranosyl sulfenamide oxide compounds wherein the variable A is oxygen. Methods of synthesis of compounds of general formula (I), pharmaceutical compositions containing them and methods of using them to treat patients suffering a microbial infection are also disclosed.

Description

NOVEL SULFENAMIDE OXIDES

Technical Field The present invention relates to novel sulfenamide oxides that have physiological activity, particularly an antimicrobial action, methods for their synthesis, pharmaceutical compositions containing them and method of treatment of patients, in particular, those suffering a microbial infection.

Background Art Many bacterial diseases once thought to be on the decline are beginning to re-emerge and annually devastate populations in many countries. This problem is amplified by the emergence of many new drug resistant strains of the microorganisms that cause these diseases. Our interest in the development of carbohydrate-based antimicrobial agents (see, for example, von Itzstein, u, et al . , 1993; Kok, Campbell, Mackey, & von Itzstein, 1996; Fazli, Bradley et al . , 2001) and in glycofuranose chemistry (Owen & von

Itzstein, 2000) has led to the discovery of a new class of antimicrobial agents described below. Although significant chemistry and biology has been published (see, for example, Marino, Marino, Miletti, Alves, Colli, & de Lederkremer, 1998; Miletti, Marino, Marino, de

Lederkremer, Colli & Alves, 1999; Zhang & Liu, 2001; Brimacombe, Gent & Stacey, 1968; Brimacombe, Da ' aboul & Tucker, 1971; Lemieux & Stick, 1975; de Lederkremer, Cirelli & Sznaidman, 1986; Shin & Perlin, 1979; de Lederkremer, Cicero & Varela, 1990; de Lederkremer, Marino & Marino, 2002; Pathak, Pathak, Suling, Gurcha, Morehouse, Besra, Maddry & Reynolds, 2002; Ernst, Hart & Sinay, 2000) in the area of glycofuranose chemistry and biology none to date has provided compounds that are clinically useful antimicrobial medicines. Carbohydrate mimics based on isosteres of the ring structure are well known in the literature and often present interesting biological activities (see, for example, Chapleur, 1998; Lillelund, Jensen, Liang, & Bols, 2002; Kok, Campbell, Mackey, & von Itzstein, 1996) .

Disclosure of the Invention The present invention is concerned generally with novel sulfenamide oxides that have physiologic activity, in particular, an antimicrobial action. In a first aspect of the present invention there is provided a compound of general formula (I) :

wherein Ri and R₂ are independently selected from the group consisting of hydrogen, optionally substituted alkyl which may be interrupted by one or more heteroatoms or functional groups selected from the group consisting of 0, S, -N=, NR₇ and - (Y)_mC= (Z) (T) _n- , optionally substituted alkenyl which may be interrupted by one or more heteroatoms or functional groups selected from the group consisting of O, S, -N=, NR₇ and - (Y)_mC= (Z) (T)_n- , optionally substituted aralkyl which may be interrupted within the alkyl moiety by one or more heteroatoms or functional groups selected from the group consisting of O, S, -N=, NR₇ and - (Y) _mC= (Z) (T) _n- , optionally substituted heterocyclic, optionally substituted aryl, optionally substituted acyl and a carbohydrate moiety; or Ri and R₂ together with the nitrogen atom from which they depend form a saturated or unsaturated, optionally substituted heterocyclic group which may include additional heteroatoms selected from the group consisting of O, N and S; A is selected from the group consisting of O, S, SO, S0₂, Se, Te, NR₈, CR₉R'₉/ N->0 and C (O) ; Xi is selected from the group consisting of OR₃, SR₃, NR₃R'₃, hydrogen, halogen, - (Y)_mC= (Z) (T) _nR₃, - N(C=(Z) (T)_nR₃)₂, N₃, CN, OCN, SCN, OS0₃R₃, OS0₂R_3/ OP0₃R₃R'₃, OP0₂R₃R'₃, S(0)R₃, S(0)₂R₃, S(0)₂OR₃, P0₃R₃R'₃, NR₃NR'₃R"₃ SNR₃R'₃, NR₃SR'₃, SSR₃ and R₃, or is an oxo group, =S, =NOR₃ or =CR₃R'₃ and X_x ' is absent, or Xi is C=(Z) and R₂ is bonded thereto so as to form a cyclic moiety - C=(Z)NRιS(0)_p-; X₂ is selected from the group consisting of OR₄, SR₄, NR₄R'₄, hydrogen, halogen, - (Y)_mC= (Z) (T)_nR₄, -

N(C=(Z) (T)_nR₄)₂, N₃, CN, OCN, SCN, OS0₃R₄, OS0₂R₄, OP0₃R₄R'_4/ OP0₂R₄R'₄, S(0)R₄, S(0)₂R₄, S(0)₂OR₄, P0₃R₄R'₄, NR₄NR'₄R"₄, SNR₄R'_4/ NR₄SR'₄, SSR₄ and R₄, or is an oxo group, =S, =NOR₄ or =CR₄R' ₄ and X₂ ' is absent; X₃ and X₃ ' are independently selected from the group consisting of OR₅, SR₅, NR₅R'₅, hydrogen, halogen, - (Y)_mC=(Z) (T)_nR_Ξ, -N(C=(Z) (T)_nR₅)₂, N₃, CN, OCN, SCN, 0S0₃R_s, OS0₂R₅, OP0₃R₅R'₅, OP0₂R₅R'₅, S(0)R₅, S(0)₂R₅, S(0)₂OR₅, P0₃R₅R'₅, NR₅NR ₅R''5/ SNR₅R'₅, NR₅SR'₅, SSR₅ and R₅, or X₃ is an oxo group, =S, =NOR₅ or =CR₅R' ₅ and X₃ ' is absent; X₄ is selected from the group consisting of OR_s, SR₆, NR₆R'_S, hydrogen, halogen, - (Y)_mC= (Z) (T) _nR₆, - N(C=(Z) (T)_nR₆)₂, N₃, CN, OCN, SCN, OS0₃R₆, OS0₂R₆, OP0₃R₆R' ₆, OP0₂R₆R'₆, S(0)R₆, S(0)₂R₆, S(0)₂OR₆, P0₃R₆R'₆, NR₆NR' ₆R" ₆, SNR_S '₆Λ NR_SSR'₆, SSR₆ and R_s, or is an oxo group, =S, =NOR₆ or =CR₅R' ₆ and X₄ ' is absent; X₅ is selected from the group consisting of hydrogen, CN, -C=(Z) (T)_nR_u, S(0)Rn, S(0)₂Rιι, S(0)₂0R_1X, POsRiiR'n, optionally substituted alkyl, optionally substituted alkaryl, optionally substituted aryl, optionally substituted aralkyl, and optionally substituted acyl; Xi ' , X₂ ' X4 ' and X₅ ' are the same or different and are selected from the group consisting of hydrogen, CN, optionally substituted alkyl, optionally substituted alkaryl, optionally substituted aryl, optionally substituted aralkyl, and optionally substituted acyl; or one of i and X₂, X₂ and X₅ ' , X₅ ' and A when A contains a carbon or nitrogen atom, X₅ and A when A contains a carbon or nitrogen atom, and X₅ and Xi together constitute a double bond, or X₅ ^■ and X₄ or X₃ and X₄ together constitute a double bond, or Ri and Xi, R₂ and X_{l t} Ri and X₂, R₂ and X₂, Rx and X₅, R₂ and X₅, Ri and X₅' , R₂ and X₅' , _x and X₂, X₂ and X₃, X₂ and X₄, X₃ and X₄, Xi and X_x' , X₂ and X₂' , X₃ and X₃' or X₄ and X₄' together form part of a ring structure which optionally includes at least one heteroatom selected from 0, S and N and is optionally substituted; m and n are independently zero or one and Y, Z and T are independently selected from the group consisting

p is 1 or 2 q is 0 or 1; K_3/ R _3ι K ₃, R₄, R ₄, R ₄, R₅, R ₅, R '₅, R₅, R g, R''_e, R₇, R₈, R9 , R's, io R11 and R' n are the same or different and are selected from the group consisting of hydrogen, optionally substituted alkyl which may be interrupted by one or more heteroatoms or functional groups selected from the group consisting of 0, S, -N=, NR₇ and - (Y) _mC= (Z) (T) _n- , optionally substituted alkenyl which may be interrupted by one or more heteroatoms or functional groups selected from the group consisting of 0, S, -N=, NR₇ and - (Y)_mC= (Z) (T) _n- , optionally substituted aryl, optionally substituted heterocyclic, optionally substituted aralkyl which may be interrupted within the alkyl moiety by one or more heteroatoms or functional groups selected from the group consisting of 0, S, -N=, NR₇ and -(Y)_mC=(Z) (T)_n-, optionally substituted acyl and a carbohydrate moiety; with the proviso that at least two of X_1# X₂, X₃ and X₄ are other than hydrogen or a group linked to the ring through a carbon-carbon bond; or a pharmaceutically acceptable salt thereof. It will be appreciated that the manner of representing substituents in the foregoing general formula does not imply any particular stereochemistry or orientation for the substituents. The term "alkyl" used either alone or in a compound word such as "optionally substituted alkyl" or

"optionally substituted cycloalkyl" denotes straight chain, branched or mono- or poly- cyclic alkyl. Examples of straight chain and branched C alkyl include methyl. ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, amyl, isoamyl, seσ-amyl, 1, 2-dimethylpropyl,

1, 1-dimethylpropyl, hexyl, 4-methylpentyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 1, 1-dimethylbutyl, 2,2- dimethylbutyl, 3 , 3 -dimethylbutyl, 1, 2 -dimethylbutyl, 1,3- dimethylbutyl, 1, 2 , 2-trimethylpropyl, 1,1,2- trimethylpropyl, heptyl, 5-methylhexyl, 1-methylhexyl, 2 , 2-dimethylpentyl, 3, 3-dimethylpentyl, 4,4- dimethylpentyl, 1, 2 -dimethylpentyl, 1, 3-dimethylpentyl, 1, 4-dimethylpentyl, 1, 2 , 3 - trimethylbutyl, 1,1,2- trimethylbutyl, nonyl, 1-, 2-, 3-, 4-, 5-, 6- or 7- methyloctyl, 1-, 2-, 3-, 4- or 5-ethylheptyl, 1-2- or 3- propylhexyl, decyl, 1-, 2-, 3-, 4-, 5-, 6-, 7- and 8- methylnonyl, 1-, 2-, 3-, 4-, 5- or 6-ethyloctyl, 1-, 2-,

3- or 4-propylheptyl, undecyl 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-methyldecyl, 1-, 2-, 3-, 4-, 5-, 6- or 7- ethylnonyl, 1-, 2-, 3-, 4- or 5-propyloctyl, 1-, 2- or 3- butylheptyl, 1-pentylhexyl, dodecyl, 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8-, 9- or 10-methylundecyl, 1-, 2-, 3-, 4-, 5-, 6- , 7- or 8-ethyldecyl, 1-, 2-, 3-, 4-, 5- or 6-propylnonyl, 1-, 2-, 3- or 4-butyloctyl, 1-2-pentylheptyl and the like. Examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl and cyclodeσyl and the like. The term "alkenyl" used either alone or in compound words such as "alkenyloxy" denotes groups formed from straight chain, branched or cyclic alkenes including ethylenically mono-, di- or poly-unsaturated alkyl or cycloalkyl groups as defined above. Examples of C₄.₃₀ alkenyl include butenyl, iso-butenyl, 3-methyl-2-butenyl, 1-pentenyl, cyclopentenyl, 1-methyl-cyσlopentenyl, 1- hexenyl, 3-hexenyl, cyclohexenyl, 1-heptenyl, 3-heptenyl, 1-octenyl, cyclooctenyl, 1-nonenyl, 2-nonenyl, 3-nonenyl, 1-decenyl, 3-decenyl, 1, 3 -butadienyl, l-4,pentadienyl, 1, 3-cyclopentadienyl, 1, 3-hexadienyl, 1, 4-hexadienyl, 1,3- cyclohexadienyl, 1, 4-cyclohexadienyl, 1,3- cycloheptadienyl, 1, 3, 5-cycloheptatrienyl and 1,3,5,7- cyclooctatetraenyl . The term "acyl" used either alone or in compound words such as "optionally substituted acyl" or "optionally substituted acyloxy" denotes an aliphatic acyl group or an acyl group containing an aromatic ring, which is referred to as aromatic acyl, or a heterocyclic ring, which is referred to as heterocyclic acyl, preferably Cι_₃₀ acyl. Examples of acyl include straight chain or branched alkanoyl such as formyl, acetyl, propanoyl, butanoyl, 2- methylpropanoyl, pentanoyl, 2, 2-dimethylpropanoyl, hexanoyl, heptanoyl, octanoyl, nonanoyl, decanoyl, undecanoyl, dodecanoyl, tridecanoyl, pentadecanoyl, hexadecanoyl, heptadecanoyl, octadecanoyl, nonadecanoyl and icosanoyl; cycloalkylcarbonyl such as cyclopropylcarbonyl cyclobutylcarbonyl, cyclopentylcarbonyl and cyclohexylcarbonyl; aroyl such as benzoyl, toluoyl and naphthoyl; aralkanoyl such as phenylalkanoyl (e.g. phenylacetyl, phenylpropanoyl, phenylbutanoyl , phenylisobutyl, phenylpentanoyl and phenylhexanoyl) and naphthylalkanoyl (e.g. naphthy1acetyl, naphthylpropanoyl and naphthylbutanoyl) ; aralkenoyl such as phenylalkenoyl (e.g. phenylpropenoyl, phenylbutenoyl, phenylmethacrylyl, phenylpentenoyl and phenylhexenoyl and naphthylalkenoyl (e.g. naphthylpropenoyl, naphthylbutenoyl and naphthylpentenoyl) ; heterocycliccarbonyl; heterocyclicalkanoyl such as thienylacetyl, thienylpropanoyl, thienylbutanoyl, thienylpentanoyl, thienylhexanoyl, thiazolylacetyl, thiadiazolylacetyl and tetrazolylacetyl; and heterocyclicalkenoyl such as heterocycliσpropenoyl , heterocyclicbutenoyl , heterocyσlicpentenoyl and heterocyclichexenoyl . The term "aryl" used either alone or in compound words such as "optionally substituted aryl", "optionally substituted aryloxy" or "optionally substituted heteroaryl" denotes single, polynuclear, conjugated and fused residues of aromatic hydrocarbons ("carbocyclic aryl" or "carboaryl") or aromatic heterocyclic ("heteroaryl") ring systems. Examples of carbocyclic aryl include phenyl, biphenyl, terphenyl, quaterphenyl, phenoxyphenyl, naphtyl, tetrahydronaphthyl, anthracenyl, dihydroanthracenyl, benzanthracenyl, dibenzanthracenyl, phenanthrenyl , fluorenyl, pyrenyl, indenyl, azulenyl, chrysenyl. Examples of heteroaryl include pyridyl, 4- phenylpyridyl, 3 -phenylpyridyl , thienyl, furyl, pyrryl, pyrrolyl, furanyl, imadazolyl, pyrrolydinyl, pyridinyl, piperidinyl, indolyl, pyridazinyl, pyrazolyl, pyrazinyl, thiazolyl, pyrimidinyl, quinolinyl, isoquinolinyl, benzofuranyl, benzothienyl, purinyl, quinazolinyl, phenazinyl, acridinyl, benzoxazolyl, benzothiazolyl and the like. Preferably, a carbocyclic aromatic ring system contains 6-10 carbon atoms and an aromatic heterocyclic ring system contains 1 to 4 heteratoms independently selected from N, O and S and up to 9 carbon atoms in the ring. The term "heterocyclyl" or equivalent terms such as "heterocyclic" used either alone or in compound words such as "optionally substituted saturated or unsaturated heterocyclyl" denotes monocyclic or polycyclic heterocyclyl groups containing at least one heteroatom atom selected from nitrogen, sulphur and oxygen. Suitable heterocyclyl groups include N-containing heterocyclic groups, such as, unsaturated 3 to 6 membered heteromonocyclic groups containing 1 to 4 nitrogen atoms, for example, pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazolyl or tetrazolyl; saturated 3 to 6-membered heteromonocyclic groups containing 1 to 4 nitrogen atoms, such as, pyrrolidinyl, imidazolidinyl, piperidino or piperazinyl; unsaturated condensed heterocyclic groups containing 1 to 5 nitrogen atoms, such as indolyl, isoindolyl, indolizinyl, benzimidazolyl, quinolyl, isoquinolyl, indazolyl, benzotriazolyl or tetrazolopyridazinyl; unsaturated 3 to 6-membered heteromonocyclic group containing an oxygen atom, such as, oxiranyl, pyranyl or furyl; unsaturated 3 to 6-membered heteromonocyclic group containing 1 to 2 sulfur atoms, such as, thienyl; unsaturated 3 to 6-membered heteromonocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, such as, oxazolyl, isoxazolyl or oxadiazolyl; saturated 3 to 6-membered heteromonocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, such as, morpholinyl; unsaturated condensed heterocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, such as, benzoxazolyl or benzoxadiazolyl; unsaturated 3 to 6-membered heteromonocyclic group containing 1 to 2 sulphur atoms and 1 to 3 nitrogen atoms, such as, thiazolyl or thiadiazolyl; saturated 3 to 6-membered heteromonocyclic group containing 1 to 2 sulphur atoms and 1 to 3 nitrogen atoms, such as, thiazolidinyl; and unsaturated condensed heterocyclic group containing 1 to 2 sulphur atoms and 1 to 3 nitrogen atoms, such as, benzothiazolyl or benzothiadiazolyl . The term "carbohydrate" denotes a carbohydrate residue or a functionalised or deoxygenated carbohydrate residue, and includes monosaσcharides and oligosaccharides . A carbohydrate residue is an acyclic polyhydroxy-aldehyde or ketone, or one of their cyclic tauto ers, and includes a compound resulting from reduction of the aldehyde or keto group such as alditols. Oxygen atoms may be replaced by hydrogen or bonds to a halogen, nitrogen, sulfur or carbon atoms, or carbon- oxygen bonds such as in ethers or esters may be introduced. Examples of carbohydrates include but are not limited to D-galactofuranose, N-acetyl-D-galactofuranose, D-glucofuranose, Itf-acetyl-D-glucofuranose, D- galactopyranose iV- cetyl-D-galactopyranose, D-glucopyranose and iV-acetyl-D-glucopyranose and their equivalents where oxygen atoms have been replaced in selected positions with hydrogen or bonds to halogen, nitrogen, sulfur or carbon, as well as oligosaccharides containing these moieties. In this specification "optionally substituted" means that a group may or may not be further substituted with one or more functional groups such as alkyl, alkenyl, alkynyl, aryl, halo, haloalkyl, haloalkenyl, haloalkynyl, haloaryl, hydroxy, alkoxy, alkenyloxy, aryloxy, benzyloxy, haloalkoxy, haloalkenyloxy, haloaryloxy, nitro, nitroalkyl, nitroalkenyl, nitroalkynyl, nitroaryl, nitroheterocyclyl, amino, alkylamino, dialkylamino, alkenyla ino, alkynylamino, arylamino, diarylamino, benzylamino, dibenzylamino, acyl, alkenylacyl, alkynylacyl, arylacyl, acylamino, diacylamino, acyloxy, alkylsulphonyloxy, arylsulphenyloxy, heterocyclyl, heterocycloxy, heterocyclamino, haloheterocyclyl, alkylsulphenyl, arylsulphenyl, σarboalkoxy, carboaryloxy, mercapto, alkylthio, benzylthio, acylthio, phosphorus- containing groups and the like, and including groups such as oxo, =S, =N- , where appropriate, particularly as substituents in ring structures such as lactones, lactarns and cyclic imides, provided that none of the substituents outlined above interferes with the formation of the subject compound. Any of the moieties whose length is defined in terms of the number of carbon atoms present may possess any number of carbon atoms within the specified range. Nevertheless, within this range certain species will be preferred due to factors such as availability and cost of precursors and ease of synthesis, as well as efficacy. In particular, such moieties containing 4 to 24 carbon atoms, preferably 6 to 12 carbon atoms, more preferably 8 to 10 carbon atoms and most preferably 8 carbon atoms are preferred for reasons of cost and availability of precursors, ease of synthesis and efficacy. In an embodiment one or both of Ri and R₂ is alkyl. In a further embodiment one or both of Rx and R₂ is C_4-30 alkyl, and may be C₆-ι₂ alkyl or C₈-ι₀ alkyl. Furthermore one or both of Ri and R₂ may be aralkyl, alkyl interrupted by one or more heteroatoms or functional groups selected from the group consisting of O, S, -N=, NR₇, and -(Y)_mC=(Z) (T)_n, alkenyl or R and R₂ together with a nitrogen atom from which they depend may form an optionally substituted saturated or unsaturated heterocyclic group, for example, a cyclic imide or a laσtam. If one or both Ri and R₂ is alkenyl it may be C₄_₃₀ alkenyl, in a further embodiment, C₆.₁₂ alkenyl and in a still further embodiment C₈_ι₀ alkenyl. In the case of one or both Ri and R₂ being alkyl interrupted by one or more of heteroatoms or functional groups, the heteroatom may be oxygen, and , in an embodiment, Ri and/or R₂ may have the formula CH₃ (CH₂) _x O (CH₂)_y0 (CH₂) _z. Equally, if one of R₃ , R'_3/

R' ' 3/ ₄1 R' ₄1 R' ' it 51 R' 5# R' ' 5/ Re, R 6, R ' e 1 7/ s/ 9 R'₉Λ R_IO R₁₁ and R' _1X is alkyl, alkenyl, aralkyl or alkyl or alkenyl interrupted by one or more heteroatoms or functional groups, embodiments are as set out for Ri and

R₂. In an embodiment the amine portion of the sulfenamide oxide is tethered to the carbohydrate moiety through an additional linkage. While the amine moiety may be tethered by linkage to any position in the carbohydrate moiety, linkage to the C position through either Ri or R₂ forming a ring together with X_x is preferred. By way of example only, the linkage may take the form of an optionally substituted alkyl chain being linked to end of a functional group located in position 2 of the carbohydrate ring and linked to a functional group located within Ri or R₂. In an embodiment X_x is OR₃. Advantageously R₃ is hydrogen or optionally substituted acyl. In an embodiment X₂ is OR₄. Advantageously, R₄ is hydrogen or optionally substituted acyl. In an embodiment X₃ is OR₅. Advantageously, R₅ is hydrogen or optionally substituted acyl. In an embodiment X₄, when present, is OR₆. Advantageously, R₆ is hydrogen or optionally substituted acyl . In an embodiment any one of the substituents R₃, R₄, R₅ and R_s is optionally substituted acyl, in particular, optionally substituted acyl where the substituent on the acyl group effects the lipophilicity or water solubility of the compound. By way of example, preferred compounds include amino acid esters where the amino acid side chain is selected to provide a predetermined lipophilicity for the compound. The amino acid side chains envisaged include all of the natural occurring amino acid side chains as well as common synthetic amino acids. Alternatively, the compounds maybe succinnyl esters terminating in amides that improve water solubility. In an embodiment p is 2 and the compounds are sulfonamides . Alternatively, p is 1 and the compounds are sulfinamides . In a further embodiment the compounds of the invention are galactofuranosyl compounds, and therefore have the configuration illustrated in general formula (la) :

Alternatively, the compounds of the invention are glucofuranosyl derivatives having the general formula (lb) :

Advantageously the sulfenamide oxide of general formula (I) is selected from the oxides of group consisting of iV,JV-dibutyl-S- (2, 3 , 5, 6-tetra-O-benzoyl-β-D- galactofuranosyl) sulfenamide, N , N- di.hex.yl - S - (2,3,5,6- tetra-O-acetyl-β-D-galactofuranosyl) sulfenamide, N,N- dioctyl-S- (2,3,5, 6-tetra-O-benzoyl-β-D- galactofuranosyl) sulfenamide, J\T,iV-didecyl-S- (2,3,5,6- tetra-O-acetyl-β-D-galactofuranosyl) sulfenamide, N,N- dibenzyl-S- (2,3,5, 6- tetra-0-benzoyl-β-D- galactofuranosyl) sulfenamide, iV,JW-di (2- ethoxyethoxyethyl) -S- (2,3,5, 6- tetra-0-acetyl -β-D- galactofuranosyl) sulfonamide, iV^-dibutyl-S- (β-D- galactofuranosyl) sulfenamide, JV,.N-dih.exyl-£- (β-D- galactofuranosyl) sulfenamide, JN^-NT-dioctyl-S- (β-D- galactofuranosyl) sulfenamide, N,N-didecyl-S- (β-D- galactofuranosyl) sulfenamide, N,N-dibenzyl-S- (β-D- galactofuranosyl) sulfenamide, jV,_V-di (2- methoxyethoxyethyl) -S- (β-D-galactofuranosyl) sulfonamide, N,N-dioctyl-S- (2,3,5, 6- tetra-O-acetyl-β-D- glucofuranosyl) sulfenamide, and iV,-V-dioσtyl-S- (β-D- glucofuranosyl) sulfenamide and iV,iV-dioctyl-S- (2, 3-di-O- acetyl-5-O- [tert-butyldiphenylsilyl] - α-D- arabinofuranosyl) sulfonamide . In a particularly preferred embodiment of the invention the compound of general formula (I) is an oxide of N,JV-dihexyl-S- (β-D-galactofuranosyl) sulfenamide, N, N- dioctyl-S- (β-D-galactofuranosyl) sulfenamide or JV,iV-dideσyl- S- (β-D-galactofuranosyl) sulfenamide, most particularly, N,N-dioctyl-S- (β-D-galactofuranosyl) sulfenamide. In another particularly preferred embodiment the compound of general formula (I) is an oxide of thio- (A = S) or aza- (A = NR₈) analogue of N,N-dihexyl-S- (β-D- galactofuranosyl) sulfenamide, _V,-V~dioctyl-S- (β-D- galactofuranosyl) sulfenamide or N,W-didecyl-S- (β-D- galactofuranosyl) sulfenamide, most particularly of N,N- dioctyl-jS- (β-D-galactofuranosyl) sulfenamide. According to a second aspect of the present invention there is provided a method of preparation of a compound of general formula (I)

comprising reacting a compound of general formula (II) :

wherein R_x, R₂, A, p, q, Xi, Xi ' , X₂, X₂ ' , X₃ , X₃ ' , X₄, X₄ ' , X₅ and X₅ ' are as defined above; with an oxidising agent. In general, Xi, X_x ' , X₂, X₂ ' , X₃, X₃ ' , X₄, X₄ ' , X₅ and X₅ ' , are as defined above. Typically the oxidising agent is 3- chloroperbenzoic acid. A number of methods have been developed to oxidise sulfenamides as disclosed, for example, in Craine and Raban, 1989; Glass & Swedo, 1977; Haake, Gebbing, & Benack, 1979; the contents of which are incorporated herein by reference. In an embodiment R₂, R'₂, R' ' 21 R31 R' 3 R' ' 3 / 4 r R' 4 / R' ' 4 R5 R' 5 R' ' 5 Rε r R' 6 and R' ' ₆ may be a protecting group, and the process includes the further step of removing the protecting groups. Protecting groups may not always be required. However, suitable protecting groups are well known to the person skilled in the arc, and acetyl or benzoyl protecting groups are preferred. Acetyl and benzoyl protecting groups are typically removed through hydrolysis with sodium methoxide in methanol. Methods for the preparation of compounds of general formula (II) are known in the art as disclosed, for example, in Craine and Raban, 1989; Koval ' , 1996; Owen & von Itzstein, 2000; von Itzstein efc al . , 2003; Illyes et al . , 2004; the contents of which are incorporated herein by reference. An extensive array of methodologies has been developed to manipulate each position of the furanose template as disclosed, for example, in Marino, Marino, Miletti, Alves, Colli, & de Lederkremer, 1998; Miletti, Marino, Marino, de Lederkremer, Colli & Alves, 1999; Zhang & Liu, 2001; Brimacombe, Gent & Stacey, 1968; Brimacombe, Da'aboul & Tucker, 1971; Lemieux & Stick, 1975; de Lederkremer, Cirelli & Sznaidman, 1986; Shin & Perlin, 1979; de

Lederkremer, Cicero & Varela, 1990; de Lederkremer, Marino & Marino, 2002; Pathak, Pathak, Suling, Gurcha, Morehouse, Besra, Maddry & Reynolds, 2002; Ernst, Hart & Sinay, 2000; the contents of which are incorporated herein by reference. According to a third aspect of the present invention there is provided a method for the treatment of a microbial infection, comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound of general formula (I) . According to a fourth aspect of the present invention there is provided the use of a compound of general formula (I) in the manufacture of a medicament, particularly for use in the treatment of a microbial infection. As used herein, the term "therapeutically effective amount" means an amount of a compound of the present invention effective to yield a desired therapeutic response, for example to prevent or treat a disease which by administration of a pharmaceutically-active agent. The specific "therapeutically effective amount" will, obviously, vary with such factors as the particular condition being treated, the physical condition and clinical history of the subject, the type of animal being treated, the duration of the treatment, the nature of concurrent therapy (if any) , and the specific formulations employed and the structure of the compound or its derivatives . As used herein, a "pharmaceutical carrier" is a pharmaceutically acceptable solvent, suspending agent, excipient or vehicle for delivering the compound of general formula (I) to the subject. The carrier may be liquid or solid, and is selected with the planned manner of administration in mind. The compound of general formula (I) may be administered orally, topically, or parenterally in dosage unit formulations containing conventional non-toxic pharmaceutically acceptable carriers, adjuvants, and vehicles. The term parenteral as used herein includes subcutaneous, intravenous, intramuscular, intrathecal, intracranial, injection or infusion techniques. The invention also provides suitable topical, oral, aerosol, and parenteral pharmaceutical formulations for use in the novel methods of treatment of the present invention. The compounds of the invention may be administered orally as tablets, aqueous or oily suspensions, lozenges, troches, powders, granules, emulsions, capsules, syrups or elixirs. The composition for oral use may contain one or more agents selected from the group of sweetening agents, flavouring agents, colouring agents and preserving agents in order to produce pharmaceutically elegant and palatable preparations. The tablets contain the active ingredient in admixture with non- toxic pharmaceutically acceptable excipients which are suitable for the manufacture of tablets. These excipients may be, for example, inert diluents, such as calcium carbonate, lactose, calcium phosphate or sodium phosphate; granulating and disintegrating agents, such as corn starch or alginic acid; binding agents, such as starch, gelatin or acacia; or lubricating agents, such as magnesium stearate, stearic acid or talc. The tablets may be uncoated, or may be coated by known techniques to delay disintegration and absorption in the gastrointestinal tract and thereby provide a sustained action over a longer period. For example, a time-delay material such as glyσeryl monostearate or glyceryl distearate may be employed. Coating may also be performed using techniques described in the U. S. Pat. Nos. 4,256,108; 4,160,452; and 4,265,874 to form osmotic therapeutic tablets for control release. The compound of general formula (I) of the invention can be administered, for in vivo application, parenterally by injection or by gradual perfusion over time independently or together. Administration may be intravenously, intra-arterial, intraperitoneally, intramuscularly, subcutaneously, intracavity, or transdermally . For in vi tro studies the agents may be added or dissolved in an appropriate biologically acceptable buffer and added to a cell or tissue. Preparations for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, and emulsions. Examples of non-aqueous solvents are propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate. Aqueous carriers include water, alcoholic/aqueous solutions, emulsions or suspensions, including saline and buffered media. Parenteral vehicles include sodium chloride solution, Ringer's dextrose, dextrose and sodium chloride, lactated Ringer's intravenous vehicles include fluid and nutrient replenishers, electrolyte replenishers such as those based on Ringer's dextrose, and the like. Preservatives and other additives may also be present such as, for example, anti-microbials, anti-oxidants, chelating agents, growth factors and inert gases and the like. The compounds of general formula (I) are antimicrobial agents which are active, in particular but not limited to, against Mycobacterium including Mycobac terium tuberculosis , M. avium intracellulare , M. fortui tum , M. abscessus and rapid growing atypical Mycobacterial strains, Nocardia , particularly Nocardia asteroides and N. nova , Staphylococcus including Staphylococcus aureus and S . aureus (Coagulas-negative) , Streptococcus spp . and Enterococci species. The compounds of general formula (I) are particularly useful in treating infections involving these organisms. Generally, the terms "treating", "treatment" and the like are used herein to mean affecting a subject, tissue or cell to obtain a desired pharmacological and/or physiological effect. The effect may be prophylactic in terms of completely or partially preventing infection, and/or may be therapeutic in terms of a partial or complete cure of an infection. "Treating" as used herein covers any treatment of, or prevention of infection in a vertebrate, a mammal, particularly a human, and includes: preventing the infection from occurring in a subject that may have been exposed to the infectious agent, but has not yet been diagnosed as affected; inhibiting the infection, ie., arresting its development; or relieving or ameliorating the effects of the infection, ie., cause regression of the effects of the infection. According to a fifth aspect of the present invention there is provided a pharmaceutical composition comprising a compound of general formula (I) and a pharmaceutically acceptable carrier. The pharmaceutical compositions according to one embodiment of the invention are prepared by bringing a compound of general formula (I) into a form suitable for administration to a subject using carriers, excipients and additives or auxiliaries. Frequently used carriers or auxiliaries include magnesium carbonate, titanium dioxide, lactose, mannitol and other sugars, talc, milk protein, gelatin, starch, vitamins, cellulose and its derivatives, animal and vegetable oils, polyethylene glycols and solvents, such as sterile water, alcohols, glycerol and polyhydric alcohols. Intravenous vehicles include fluid and nutrient replenishers. Preservatives include antimicrobial, anti- oxidants, chelating agents and inert gases. Other pharmaceutically acceptable carriers include aqueous solutions, non-toxic excipients, including salts, preservatives, buffers and the like, as described, for instance, in Remington's Pharmaceutical Sciences, 15th ed. Easton: Mack Publishing Co., 1405-1412,1461-1487 (1975) and The National Formulary XIV., 14th ed. Washington: American Pharmaceutical Association (1975) , the contents of which are hereby incorporated by reference. The pH and exact concentration of the various components of the pharmaceutical composition are adjusted according to routine skills in the art. See Goodman and Gilman's The Pharmacological Basis for Therapeutics (7th ed.). The pharmaceutical compositions are preferably prepared and administered in dosage units. Solid dosage units include tablets, capsules and suppositories. For treatment of a subject, depending on activity of the compound, manner of administration, nature and severity of the disorder, age and body weight of the subject, different daily doses can be used. Under certain circumstances, however, higher or lower daily doses may be appropriate. The administration of the daily dose can be carried out both by single administration in the form of an individual dose unit or else several smaller dose units and also by multiple administration of subdivided doses at specific intervals. The pharmaceutical compositions according to the invention may be administered locally or syste ically in a therapeutically effective dose. Amounts effective for this use will, of course, depend on the severity of the microbial infection and the weight and general state of the subject. Typically, dosages used in vi tro may provide useful guidance in the amounts useful for in si tu administration of the pharmaceutical composition, and animal models may be used to determine effective dosages for treatment of the cytotoxic side effects. Various considerations are described, eg., in Langer, Science, 249: 1527, (1990). Formulations for oral use may be in the form of hard gelatin capsules wherein the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate or kaolin. They may also be in the form of soft gelatin capsules wherein the active ingredient is mixed with water or an oil medium, such as peanut oil, liquid paraffin or olive oil . Aqueous suspensions normally contain the active materials in admixture with excipients suitable for the manufacture of aqueous suspension. Such excipients may be suspending agents such as sodium carboxymethyl cellulose, methyl cellulose, hydroxypropylmethylcellulose, sodium alginate, polyvinylpyrrolidone, gum tragacanth and gum acacia; dispersing or wetting agents, which may be (a) naturally occurring phosphatide such as lecithin; (b) a condensation product of an alkylene oxide with a fatty acid, for example, polyoxyethylene stearate; (c) a condensation product of ethylene oxide with a long chain aliphatic alcohol, for example, heptadecaethylenoxycetanol; (d) a condensation product of ethylene oxide with a partial ester derived from a fatty acid and hexitol such as polyoxyethylene sorbitol monooleate, or (e) a condensation product of ethylene oxide with a partial ester derived from fatty acids and hexitol anhydrides, for example polyoxyethylene sorbitan monooleate. The pharmaceutical compositions may be in the form of a sterile injectable aqueous or oleaginous suspension. This suspension may be formulated according to known methods using suitable dispersing or wetting agents and suspending agents such as those mentioned above. The sterile injectable preparation may also a sterile injectable solution or suspension in a non- toxic parenterally-acceptable diluent or solvent, for example, as a solution in 1, 3-butanediol . Among the acceptable vehicles and solvents which may be employed are water, Ringer's solution, and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose, any bland fixed oil may be employed, including synthetic mono-or diglycerides . In addition, fatty acids such as oleiσ acid find use in the preparation of injectables . Compounds of general formula (I) may also be administered in the form of liposome delivery systems, such as small unilamellar vesicles, large unilamellar vesicles, and multilamellar vesicles. Liposo es can be formed from a variety of phospholipids, such as cholesterol, stearylamine, or phosphatidylcholines . Compounds of general formula (I) may also be administered in combination with cyclodextrins for enhanced aqueous solubility. Dosage levels of the compound of general formula (I) of the present invention will usually be of the order of about 0.05mg to about 20mg per kilogram body weight, with a preferred dosage range between about 0.05mg to about lOmg per kilogram body weight per day (from about

0. lg to about 3g per patient per day) . The amount of active ingredient which may be combined with the carrier materials to produce a single dosage will vary, depending upon the host to be treated and the particular mode of administration. For example, a formulation intended for oral administration to humans may contain about lmg to lg of an active compound with an appropriate and convenient amount of carrier material, which may vary from about 5 to 95 percent of the total composition. Dosage unit forms will generally contain between from about 5mg to 500mg of active ingredient. It will be understood, however, that the specific dose level for any particular patient will depend upon a variety of factors including the activity of the specific compound employed, the age, body weight, general health, sex, diet, time of administration, route of administration, rate of excretion, drug combination and the severity of the particular disease undergoing therapy. In addition, some of the compounds of the invention may form solvates with water or common organic solvents. Such solvates are encompassed within the scope of the invention. The compounds of the invention may additionally be combined with other compounds to provide an operative combination. It is intended to include any chemically compatible combination of pharmaceutically-active agents, as long as the combination does not eliminate the activity of the compound of general formula (I) of this invention. According to a sixth aspect of the present invention there is provided a method of killing a microorganism, comprising exposing said microorganism to a compound of general formula (I) as defined above. Advantageously, although not limited to, the microorganism is selected from the group consisting of Mycobacterium including Mycobacterium tuberculosis , M. avium intracellulare , M. fortui tum , M. abscessus and rapid growing atypical Mycobacterial strains, Nocardia , particularly Nocardia asteroides and N. nova ,

Staphylococcus including Staphylococcus aureus and S . aureus (Coagulas-negative) , Streptococcus spp. and Enterococci species. Throughout this specification and the claims, the words "comprise", "comprises" and "comprising" are used in a non-exclusive sense, except where the context requires otherwise. It will be clearly understood that, although a number of prior art publications are referred to herein, this reference does not constitute an admission that any of these documents forms part of the common general knowledge in the art, in Australia or in any other country.

Modes for Performing the Invention The synthetic schemes employed to prepare compounds in accordance with preferred embodiments of the invention are now described in more detail. The synthesis of protected (compounds 4; Examples 1 to 6) and deprotected (compounds 5; Examples 9 to 14) galactofuranosyl sulfonamides is shown in Scheme 1. For the preparation of these examples, 1, 2 , 3, 5, 6-penta-O- acetyl-D-galactofuranose (compound 1, Acyl = acetyl;

Bakinovskii et al . , 1988) and l-S-acetyl-2 , 3 , 5, 6-tetra-O- benzoyl-1- thio-β-D-galactofuranose (compound 2, Acyl = benzoyl; Owen and von Itzstein, 2000) were prepared according to known literature methods and are shown in Scheme 1 without modification. The synthesis of protected (compound 7; Example 7) and deprotected (compound 8; Example 15) glucofuranosyl sulfonamides is shown in Scheme 2. The synthesis of a protected (compound 13; Example 8) arabinofuranosyl sulfonamide is shown in Scheme 3. For the preparation of these examples, 5-0- (t- butyldiphenylsilyl) -D-arabinofuranose (compound 9) was prepared according to known literature methods and is shown in Scheme 2 without modification. The synthesis of a protected (compound 15, Example 16) and deprotected (compound 16, Example 17) glucofuranosyl sulfonamides is shown in Scheme 4. All new compounds gave the expected spectroscopic data.

1 Acyl = Ac, Bz 2 Acyl =Ac, Bz

R¹ = R² = C₄H₉ ; C₆Hι ₃ ; C₈Hι₇ ; C10H21 ; CH₂Ph ; CH2CH2OCH2CH2OCH3

Scheme 1 .Reagents and Conditions: a) SnCl₄ or BF₃.Et₂θ, HSAc, CH₂C1₂ , 0 °C to rt, 1 to 6 h, N₂; b) BrCH (COOEt) ₂, HNR¹^, DMF, THF, or MeOH, rt, 4 h to 7 d; c) MCPBA, CH₂Cl₂, reflux, 1-4 h; d) NaOMe, MeOH, rt, 2 h, N₂.

6 R =R²= C₈H₁₇ 7 R = R² = C_R 8B^π17 8 R¹ = R² = C_RH 17

Scheme 2 Reagents and Conditions: a) MCPBA, CH₂C1₂, reflux, 4 h; b) NaOMe, MeOH, rt, 2 h, N₂.

TBDPS

1Q 11

12 R =R² = C₈H₁₇ 13 R = = R² = C₈H. I7 14 R =R² = C₈H₁₇

Scheme 3 .Reagents and Conditions : a) pyridine, Ac₂0, 0 °C, 1 h, N₂; b) BF₃.Et₂θ, CH₂C1₂, HSAc, rt, 5 h, Ar; c) BrCH (COOEt) ₂, HN(C₈H₁₇)₂, MeOH, rt, 3 h, Ar; d) MCPBA, CH₂C1₂, reflux, 4 h; e) i. TBAF, AcOH, THF, rt, 6 h, N₂; ii. NaOMe, MeOH, rt, 2 h, N₂.

6 R¹ = R² = C₈H ₇ 15 R¹ = R²= C₈H₁₇ 16 R¹ = R²= C₈H_|7 Scheme 4 Reagents and Condi tions : a) i. W-chlorosuccinimide, CH₂C1₂, 0 °C, 30 min; ii . H₂0/KHC0₃, According to Haake et al . , 1979; b) NaOMe, MeOH, rt, 2 h, N₂.

General procedure for the preparation of sulfenamides; exemplified for reaction of l -S-acetyl -2 , 3 , 5 , 6- tetra-O- acetyl -l - thio- -D-galactofuranose (2, Acyl = acetyl ) : To a solution of l-S-acetyl-2, 3 , 5, 6-tetra-O- acetyl-1- thio-β-D-galactofuranose (2) (2.0 g) in solvent (60 mL) is added diethyl bromomalonate (1.5 equiv.) and amine (3 equiv.), and the reaction is stirred at room temperature. Upon completion of the reaction the volatile compounds are removed under reduced pressure and the residue is chromatographed on silica.

General procedure for the oxidation of sulfenamides to the corresponding sulfonamides : To a solution of the protected sulfenamide (0.5 mmol) in dichloromethane (20 L) is added meta- chloroperoxybenzoic acid (3 equiv.) and the mixture is heated under reflux. Upon completion of the reaction, the reaction mixture is diluted to 50 mL with dichloromethane and quenched with saturated aqueous sodium hydrogen carbonate (20 mL) . The organic phase is separated and dried (NaS0₄) , filtered, concentrated under reduced pressure, and the residue is chromatographed on silica.

Example 1

N,W-Dibutyl -S- (2,3,5, 6- tetra-O-benzoyl-β-D- galactofuranosyl) sulfenamide (3, R¹ = R² = C₄H₉) : Prepared according to the general procedure by reaction of l-S-acetyl-2 , 3 , 5, 6-tetra-O-benzoyl-β-D- galactofuranose (2) with diethyl bromomalonate and dibutyla ine in dry DMF for 23 h, at room temperature under Ar. The residue was chromatographed on silica (6:1 hexanes/EtOAc) to furnish iV,JV-dibutyl-S- (2 , 3 , 5, 6- tetra-O- benzoyl-β-D-galactofuranosyl) sulfenamide (39%). R_f 0.26 (2:1 hexanes/EtOAc) . ^XH NMR (300 MHz, CDC1₃) : δ.0.86 (6H, t, 2 x CH₃) , 1.22-1.34 (4H, m, 2 x CH₂) , 1.52-1.62 (4H, m, 2 x CH₂) , 2.91-3.00 (4H, m, 2 x CH₂) , 4.68-4.82 (3H, m, H- 4, H-6, H-6'), 5.30 (1H, dd, J₂,₃ 2.4, <J_2/1 3.0 Hz, H-2) , 5.67 (1H, dd, J₃,₂ 2.1, -J_3/4 5.1 Hz, H-3), 5.78 (1H, d, J_lr2 3.0 Hz, H-l) , 6.05-6.09 (1H, m, H-5) , 7.28-7.61 (12H, m, m,p Ar-H), 7.87-7.98 (m, 4H, o Ar-H), 8.03-8.11 (m, 4H, o Ar-H) .

_V,JV-Dibutyl-S- (2 , 3 , 5, 6- tetra-O-benzoyl-β-D- galactofuranosyl) sulfonamide (4, R¹ = R² = C₄H₉) : Prepared from JW,-V-dibutyl-S- (2 , 3, 5, 6-tetra-O- benzoyl-β-D-galactofuranosyl) sulfenamide (3, R¹ = R² = C₄H₉) according to the general procedure. Yield: 75%. R_f. 0.24 (4:1, hexanes/EtOAc) . ^Η NMR (300 MHz, CDCl₃) : δ.0.87 (6H, t, 2 x CH₃) , 1.18-1.31 (4H, m, 2 x CH₂) , 1.47-1.59 (4H, m, 2 x CH₂) , 3.15-3.35 (4H, m, 2 x CH₂) , 4.65-4.76 (2H, m, H- 6, H-6') , 5.06 (1H, dd, J_{4 5} 4.5, ιT₄,₃ 5.4 Hz, H-4) , 5.19 (1H, d, J_{1 2} 2.1 Hz, H-l), 5.78 (1H, dd, J_3/2 2.1, «J_3/4 5.4 Hz, H-3), 6.00 (1H, m, H-5), 6.22 (1H, t, J₂,ι = J₂,₃ 2.1 Hz, H-2), 7.29-7.60 (m, 12H, m,p Ar-H), 7.89-7.96 (m, 4H, o Ar-H), 8.04-8.12 (m, 4H, o Ar-H) .

Example 2

^iV-Dihexyl-S- (2 , 3 , 5, 6- tetra-O-acetyl-β-D- galactofuranosyl) sulfenamide (3, R¹ = R² = CgH₁₃) : Prepared according to the general procedure by reaction of l-S-acetyl-2 , 3 , 5, 6- tetra-O-acetyl-β-D- galactofuranose (2) with diethyl bromomalonate and dihexylamine in methanol for 4 h at room temperature . The residue was chromatographed on silica (3:1 hexanes/EtOAc) to furnish _NT,iV-dihexyl-S- (2, 3, 5, 6-tetra-O-acetyl-β-D- galactofuranosyl) sulfenamide (56%). R_f 0.29 (3:1 hexanes/EtOAc) . iV,W-Dihexyl-S- (2,3,5, 6- tetra-O-acetyl- β-D- galactofuranosyl) sulf onamide (4, R¹ = R² = C₆H₁₃) : Prepared from iV,iY-dihexyl-S- (2, 3 , 5, 6-tetra-O- acetyl-β-D-galactofuranosyl) sulf enamide (3, R¹ = R² = C₆Hι₃) according to the general procedure. Yield: 60%. R_f 0.27 (3:1 hexanes/EtOAc) . ¹H NMR (300 MHz, CDC1₃) : δ.0.89 (6H, t, 2 x CH₃) , 1.23-1.37 (12H, m, 6 x CH₂) , 1.55-1.63 (4H, m, 2 x CH₂) , 2.05, 2.09, 2.11, 2.13 (4 x 3H, 4 x s, 4 x OAc), 3.12-3.30 (4H, m, 2 x CH₂) , 4.17 (1H, dd, J₆,₅ 6.9, J₆,6< 11.7 Hz, H-6), 4.27 (1H, dd, J₆, ,₅ 5.1, J₆, ,₆ 11.4 Hz, H-6') , 4.61 (1H, dd, J-₄,s 3.6, J₄,₃ 7.5 Hz, H-4) , 4.82 (1H, d, J_lι2 3.6 Hz, H-l), 5.18 (1H, dd, «7₃,₂ 3.9, ^" _{3 4} 7.5 Hz, H-3), 5.27 (1H, m, H-5), 5.84 (1H, t, J_2rl = J₂,₃ 3.9 Hz, H-2) .

Example 3

N,iV-Dioctyl-S- (2,3,5, 6- tetra-O-benzoyl-β-D- galactofuranosyl) sulfonamide (4, R¹ = R² = C₈H₁₇) : Prepared from -V,iV-dioctyl-S- (2 , 3 , 5 , 6-tetra-O- benzoyl-β-D-galactofuranosyl) sulfenamide (3, R¹ = R² = C₈Hι₇; von Itzstein et al . , 2003) according to the general procedure. Yield: 77%. R_£ 0.62 (3:1 hexanes/EtOAc) . ^Η NMR (300 MHz, CDCl₃) : δ 7.28 - 8.13 (m, 20 H, 4 x C0₂Ph) , 6.22 (app t, 1 H, J 2.2 Hz, H-2), 5.99 (m, 1 H, H-5), 5.78 (dd, 1 H, .7₃,₄ 5.4, J₃,₂ 2.0 Hz, H-3), 5.19 (d, 1 H, J_lι2 2.1 Hz, H-l), 5.06 (dd, 1 H, ^" _{4 5} 4.4, -J₄,₃ 5.3 Hz, H-4), 4.65-4.77 (m, 2 H, H-6 and H-6'), 3.12-3.37 (m, 4 H, N(CH₂)₂), 1.53 (m, 4 H, 2 x CH₂, dioctyl chain), 1.14-1.32 (m, 20 H, 10 x CH₂, dioctyl chain), 0.86 (app t, 6 H, J 6.5, J 6.9 Hz, 2 x CH₃) ; LRMS (ESI): ^m/_z 906 [ (M + Na) ⁺ 100%] .

Example 4

ΪV,iV-Didecyl-S- (2,3,5, 6- tetra-O-acetyl-β-D- galactofuranosyl) sulfenamide (3, R¹ = R² = C₁₀H₂₁) : Prepared according to the general procedure by reaction of l-S-acetyl-2 , 3 , 5 , 6- tetra-O-acetyl-β-D- galactofuranose (2) with diethyl bromomalonate and didecylamine in methanol for 4 h at room temperature. The residue was chromatographed on silica (10:1 to 4:1 hexanes/EtOAc) to furnish N,JV-didecyl-S- (2, 3 , 5, 6- tetra-O- acetyl-β-D-galactofuranosyl) sulfenamide (74%). R_£ 0.38 (3:1 hexanes/EtOAc) .

iV,.V-Didecyl-S- (2,3,5, 6- tetra-O-acetyl-β-D- galactofuranosyl) sulfonamide (4, R¹ = R² = C₁₀H₂ι) : Prepared from JY,iV-didecyl-S- (2, 3 , 5, 6-tetra-O- acetyl-β-D-galactofuranosyl) sulfenamide (3, R¹ = R² = Cι₀H₂₁) according to the general procedure. Yield: 64%. R_£ 0.34 (3:1 hexanes/EtOAc) . ^Η NMR (300 MHz, CDC1₃) : δ.0.87 (6H, t, 2 x CH₃), 1.19-1.37 (28H, m, 14 x CH₂) , 1.49-1.65 (4H, m, 2 x CH₂) , 2.05, 2.08, 2.10, 2.13 (4 x 3H, 4 x s, 4 x OAc), 3.11-3.31 (4H, m, 2 x CH₂) , 4.17 (IH, dd, J₆,₅ 6.9, J₆,β_' H.4 Hz, H-6), 4.27 (IH, dd, J₆- ,5 5.1, J₆, ,₆ 11.4 Hz, H-6') , 4. SI (IH, dd, J₄,₅ 3.6, σ₄,₃ 7.5 Hz, H-4), 4.82 (IH, d, J_lι2 3.6 Hz, H-l), 5.18 (IH, dd, J^" ₃,₂ 4.2, ι7₃,₄ 7.5 Hz, H- 3) , 5.27 (IH, m, H-5), 5.83 (IH, t, J_2ιl = J_2ι3 3.9 Hz, H- 2) .

Example 5 iV,iV-Dibenzyl-S- (2,3,5, 6- tetra-O-benzoyl-β-D- galactofuranosyl) sulfenamide (3, R¹ = R² = CH₂Ph) : Prepared according to the general procedure by reaction of l-S-acetyl-2 , 3 , 5, 6- tetra-O-benzoyl-β-D- galactofuranose (2) with diethyl bromomalonate and dibenzylamine in dry THF for 7 days, at room temperature under Ar. The residue was chromatographed on silica (4:1 hexanes/EtOAc) to furnish iV,iV-dibenzyl-S- (2, 3, 5, 6- tetra-O- benzoyl-β-D-galactofuranosyl) sulfenamide (16%) as a pale orange syrup. R_t 0.41 (4:1 hexanes/EtOAc) . ^Η NMR (300 MHz, CDC1₃) : δ 7.20-8.20 (m, 30 H, 4 x C0₂Ph and N(CH₂)₂(Ph)₂) , 6.05 (m, 1 H) , 5.97 (dd, 1 H, J 3.4, J 6.5 Hz), 5.76 (d, 1 H, J 3.6 Hz), 5.65 (bd, 1 H, J 4.7 Hz), 5.49 ( , 2 H) , 5.35 (d, 1 H, J 6.6 Hz), 4.71 (m, 3 H) , 4.58 (app t, 1 H, J 3.2 Hz), 4.19-4.40 (m, 5 H) , 3.83 (d, 2 H, J 14.3 Hz); LRMS (ESI): ^m/_z 830 [ (M + Na) ⁺ 100%], 357 (60) , 198 (58) , 808 (41) .

-V,iV-Dibenzyl-S- (2,3,5, 6- tetra-O-benzoyl-β-D- galactofuranosyl) sulfonamide (4, R¹ = R = CH₂Ph) : Prepared from JNT,iV-dibenzyl-S- (2, 3 , 5, 6- tetra-O- benzoyl-β-D-galactofuranosyl) sulfenamide (3, R¹ = R² = CH₂Ph) according to the general procedure. Yield: 52%. R_f 0.45 (hexane-EtOAc 3:1). ^λΗ. NMR (300 MHz, CDC1₃) : δ 7.18- 8.15 (m, 30 H, 4 x C0₂Ph and N(CH₂Ph)₂), 6.30 (app t, 1 H, J 2.2 Hz, H-2), 6.01 (m, 1 H, H-5), 5.80 (dd, 1 H, J₃,₄ 5.4, J₃,₂ 2.1 Hz, H-3), 5.13 (m, 1 H, H-4), 5.11 (d, 1 H, -7ι,₂ 2.3 Hz, H-l), 4.69 (d, 2 H, J 5.9 Hz, H-6 and H-6'), 4.49 (d, 2 H, J 15.4 Hz, N(CH₂Ph)₂), 4.31 (d, 2 H, J 15.4 Hz, N(CH₂Ph)₂); LRMS (ESI): ^m/_z 862 [ (M + Na) ⁺ 100%]; Anal. Calcd for C₄₈H₄ιNO_ι:LS : C, 68.84; H, 4.92; N, 1.67. Found: C, 68.50; H, 4.96; N, 1.58.

Example 6 ΛT,JV-Di (2-methoxyethoxyethyl) -S- (2,3,5, 6- tetra-O-acetyl-β-D- galactofuranosyl) sulfenamide (3, R¹ = R² = CH₂CH₂OCH₂CH₂OCH₃) : Prepared according to the general procedure by reaction of l-S-acetyl-2, 3 , 5, 6- tetra-O-acetyl-β-D- galactofuranose (2) with diethyl bromomalonate and N,N- di (2-methoxyethoxyethyl) amine in methanol for 19 h at room temperature. The residue was chromatographed on silica (EtOAσ) to furnish N,N- (2-methoxyethoxyethyl) -S- (2, 3, 5, 6- tetra-O-acetyl-β-D-galactofuranosyl) sulfenamide (72%) as a light golden oil. R_t 0.32 (EtOAc) . ^XH NMR (300 MHz,

CDC1₃) : δ 1.91, 1.93, 1.96, 1.99 (4 x 3H, 4 x s, 4 x OAc), 3.08 (4H, t, J^" = 6 Hz, NCH₂CH₂) , 3.23 (6H, s, OMe) , 3.30- 3.60 (12H, m, OCH₂) , 4.00-4.25 (3H, m, H-5, H-6, H-6^{^}), 4.92 (2H, m, H-2, H-3), 5.19 (IH, m, H-5), 5.29 (IH, d, «7ι,₂ 3.3 Hz, H-l) . N,N-O± (2-methoxyethoxyethyl) -S- (2, 3, 5, 6 - tetra-O- acetyl -β-D- galactofuranosyl) sulf onamide (4, R¹ = R² = CH₂CH₂OCH₂CH₂OCH₃) : Prepared from N,N-dϊ (2-methoxyethoxyethyl) -S- (2,3,5, 6- tetra-O- acetyl -β-D-galactofuranosyl) sulfenamide (3, R¹ = R² = CH₂CH₂OCH₂CH₂OCH₃) according to the general procedure (reaction for 1 h) . Yield: 76%. R_ε 0.24 (ethyl acetate) . ^XH NMR (300 MHz, CDC1₃) : δ 1.95, 1.97, 1.99, 2.01 (4 x 3H, 4 x s, 4 x OAc), 3.29 (6H, s, OMe) , 3.40- 3.70 (16H, m, OEt) , 4.10-4.25 (2H, m, H-6, H-6"), 4.53 (2H, dd, ι7_3/4 7.8, J_iι5 3.6 Hz, H-4), 5.10 (IH, dd, J₂,₃ 4.2, -₄,₅ 3.6 Hz, H-3), 5.18 (IH, m, H-5), 5.28 (IH, d, J_ll2 3.6 Hz, H-l), 5.75 (IH, dd, J_lι2 3.6, J^" _2/3 4.2 Hz, H-2) .

Example 7

N,N-Dioctyl~S- (2,3,5, 6-tetra-O-acetyl-β-D- glucofuranosyl) sulfonamide (7, R¹ = R² = C₈H₁₇) : Prepared from N,W-dioctyl-S- (2 , 3 , 5, 6- tetra-O-acetyl-β- D-glucofuranosyl) sulfenamide (6, R¹ = R² = C₈Hι₇; von Itzstein et al . , 2003) according to the general procedure. Yield: 39%. R_£ 0.21 (3:1 hexanes/EtOAc) . ^XH NMR (300 MHz, CDC1₃) : δ.0.87 (6H, t, 2 x CH₃) , 1.22-1.34 (20H, m, 10 x CH₂) , 1.51-1.64 (4H, m, 2 x CH₂) , 2.00, 2.08, 2.09, 2.13 (4 x 3H, 4 x s, 4 x OAc), 3.14-3.33 (4H, m, 2 x CH₂) , 4.13 (IH, dd, J-_s,₅ 4.8, <T₆.₆, 12.3 Hz, H-6), 4.39 (IH, dd, J₄,₃ 4.2, ^" ₄,₅ 9.0 Hz, H-4), 4.56 (IH, dd, J₆, _r5 2.1, J₆> ,₆ 12.3 Hz, H-6') , 4.77 (IH, d, J_lι2 2.7 Hz, H-l), 5.31-5.37 (2H, m, H-3, H-5), 5.56 (IH, app. d, J_2ιl ~ J_2ι3 2.1 Hz, H-2) .

Example 8

1,2,3 -Tri-O-acetyl-5-O- (terfc-butyldiphenylsilyl) -α/β-D- arabinofuranose (10) : 5-0- (Terfc-butyldiphenylsilyl) - α/β-D-arabinose (9) (2.10 g, 5.40 mmol) was dissolved in dry pyridine (20 L) and stirred with acetic anhydride (20 mL, excess) under N₂ at 0 °C for 1 h and then at room temperature for 18 h. After this time the solvent removed under reduced pressure and the residue was chromatographed on silica (4:1 hexanes/EtOAc) to furnish 1, 2 , 3-tri-O-acetyl-5-O- (fcerfc-butyldiphenylsilyl) -α/β-D-arabinofuranose (2.67 g, 96%) as a clear syrup. R_f 0.45 (4:1 hexanes/EtOAc) . ^XH NMR (300 MHz, CDC1₃) : δ 7.33-7.22 (m, 10 H, SiPh) , 6.37 (d, 1 H, -7_1/24.7 Hz, H-lβ), 6.19 (bs, 1 H, H-lα), 5.63 (dd, 1 H, J-₃,₄6.1, ι7_3/27.2 Hz, H-3β) , 5.38 (m, I H, H-3α) , 5.33 (dd, 1 H, -7_2fι4.8, ι7₂,₃7.2 Hz, H-2β) , 5.21 (app d, 1 H, J 1.6 Hz, H-2α) , 4.24 (dd, 1 H, J 4.0, " 8.8 Hz, H-4α) , 4.12 (m, 1 H, H-4β) , 3.87 (m, 2 H, H-5α and H-5'α), 3.81 (m, 2 H, H-5β and H-5'β), 2.02-2.13 (6 x s, 18 H, 6 x OAc α and β) , 1.07 (bs, 18 H, terfc-butyl α and β) .

l-S-Acetyl-2 , 3 -di-O-acetyl-5- - (fcerfc-butyldiphenylsilyl) - 1-thio-α-D-arabinofuranose (11) : To a solution of 1, 2, 3-tri-0-acetyl-5-0- (fcerfc- butyldiphenylsilyl) - α/β-D-arabinofuranose (10) (2.10 g, 4.08 mmol) in dry DCM (20 mL) at 0 °C, under Ar was added BF₃.OEt₂ (1.2 equivalents, 4.90 mmol) . After 10 minutes thiolacetic acid (1.5 equivalents, 4.33 mL, 6.12 mmol) was added and the reaction was stirred for 5 h at room temperature under Ar. After this time the reaction was diluted with EtOAc (150 mL) and sat. aq. NaHC0₃ (150 mL) . The layers were separated and the organic layer was washed once with sat. aq. NaHC0₃ (150 mL) and once with aq. NaCI (150 L) . The organic phase was then dried over Na₂S0₄, filtered, and the solvent removed under reduced pressure. The residue was chromatographed on silica (3:1 hexanes/EtOAc) to furnish l-S-acetyl-2, 3-di-0-acetyl-5-0- (fcerfc-butyldiphenylsilyl) -1- thio-α-D-arabinofuranose (1.88 g, 87%) as a clear syrup. R_£ 0.30 (4:1 hexanes/EtOAc) .

^Η NMR (300 MHz, CDC1₃) : δ 7.65-7.73 (m, 4 H, Si(Ph)₂) , 7.34-7.46 (m, 6 H, Si(Ph)₂), 6.00 (bs, 1 H, H-l), 5.37 (m, 1 H, H-2), 5.25 (app t, 1 H, J 1.6 Hz, H-3), 4.14 ( , 1 H, H-4), 3.85 (m, 2 H, H-5 and H-5'), 2.39 (s, 3 H, SCOCH₃) , 2.11 (s, 3 H, 1 x OCOCH₃) , 2.02 (s, 3 H, 1 x OCOCH₃) , 1.06 (s, 9 H, -C(CH₃)₃) • iV,.V-Dioctyl-S- (2, 3 -di-O-acetyl-5-O- [fcerfc- butyldiphenylsilyl] - α-D-arabinofuranosyl) sulfenamide (12, R = R ⁼ C₈Hι₇) : Prepared according to the general procedure by reaction of l-S-acetyl-2, 3-di-0-aσetyl-5-0- (fcerfc- butyldiphenylsilyl) -1- thio-α-D-arabinofuranose (11) with diethyl bromomalonate and dioctylamine in dry methanol for 3 h, at room temperature under Ar. The residue was chromatographed on silica (6:1 hexanes/EtOAc) to furnish N,N-dloctyl-S- (2 , 3-di-0-acetyl-5-0- [fcerfc- butyldiphenylsilyl] -α-D-arabinofuranosyl) sulf enamide (64%) as a pale yellow syrup. R_£ 0.70 (4:1 hexanes/EtOAc) . ¹H NMR (300 MHz, CDC1₃) : δ 7.66-7.73 (m, 4 H, Si(Ph)₂) , 7.33- 7.47 (m, 6 H, Si(Ph)₂) , 5.44 (d, 1 H, J_1/2 4.1 Hz, H-l) , 5.34 (dd, 1 H, J₃,₄ 5.4, J_{3 2} 3.2 Hz, H-3) , 5.12 (dd, 1 H, J_2i3 3.2, J₂,ι 4.0 Hz, H-2) , 4.22 (m, 1 H, H-4) , 3.85 (d, 2 H, J 3.9 Hz, H-5 and H-5' ) , 2.90 (m, 4 H, N(CH₂)₂) , 2.05 (s, 6 H, 2 x OCOCH₃) , 1.18-1.63 (m, 24 H, 12 x CH₂ dioctyl chain) , 1.06 (s, 9 H, -C(CH₃)₃) , 0.87 (m, 6 H, 2 x CH₃) .

W,iV-Dioctyl-S- (2 , 3 -di-O-acetyl-5-O- [terfc- butyldiphenylsilyl] - α-D-arabinofuranosyl) sulf onamide (13, R¹ = R² = C₈Hι₇) : Prepared from iV,iV-dioctyl-S- (2 , 3 -di-O-acetyl-5-O- [terfc-butyldiphenylsilyl] -α-D-arabinofuranosyl) sulf enamide (12, R¹ = R² = C₈Hχ ) according to the general procedure.

Yield: 53%. R_f 0.61 (4:1 hexanes/EtOAc) . ^XH NMR (300

MHz, CDC1₃) : δ 7.65-7.71 (m, 4 H, Si(Ph)₂) , 7.34-7.47 (m, 6

H, Si(Ph)₂), 5.85 (app t, 1 H, J 3.4 Hz, H-2) , 5.43 (dd, 1 H, J_{3 4} 6.9, -7_3/2 3.6 Hz, H-3) , 4.85 (d, 1 H, J_lι2 3.3 Hz, H- 1) , 4.48 ( , 1 H, H-4) , 3.83 (m, 2 H, H-5 and H-5') , 3.11- 3.37 (m, 4 H, N(CH₂)₂) , 2.08 (s, 3 H, 1 x OCOCH₃) , 2.07 (s, 3 H, 1 x OCOCH₃) , 1.51-1.68 (m, 4 H, 2 x CH₂ dioctyl chain) , 1.17-1.39 (m, 20 H, 10 x CH₂ dioctyl chain) , 1.06 (s, 9 H, -C(CH₃)₃) , 0.87 ( , 6 H, 2 x CH₃) . General procedure for the deprotection of benzoate and acetate protecting groups: To a solution of the protected sulfonamide (0.5 mmol) in dry methanol (10 mL) under an atmosphere of N₂ was added one equivalent of sodium methoxide (IM solution in dry methanol) . The reaction was left to stir at room temperature for 2 h. After this time the reaction was neutralized with Amberlite (H⁺) resin. The resin was removed by filtration and the solvent removed under reduced pressure. The residue was chromatographed on silica to yield the desired deprotected compound.

General procedure for the deprotection of tert- butyldiphenylsilyl protecting groups : To a solution of the silyl protected sulfonamide (0.5 mmol) in dry THF (5 mL) under an atmosphere of N₂ is added one and a half equivalents of tetrabutylammonium fluoride (1 M solution in THF) and acetic acid (0.1 mL) . The reaction is left to stir at room temperature for 15 h, then additional acetic acid (0.5 mL) is added and the reaction is left to stir for a further 1 h. After this time the reaction mixture is evaporated under reduced pressure. The residue is chromatographed on silica to yield the desired desilylated compound.

Example 9

2V,jW-Dibutyl-S- (β-D-galactofuranosyl) sulf onamide (5, R¹ = R²

= C₄Hg) : Yield: 80%. R_f 0.36 (15:1 E t OAc /MeOH ) . ^XH NMR (300 MHz, CD₃OD) : δ .0.98 (6H, t, 2 x CH₃) , 1.30-1.43 (4H, m, 2 x CH₂) , 1.56-1.67 (4H, m, 2 x CH₂) , 3.24-3.39 (4H, m, 2 x CH₂) , 3.60-3.76 (3H, m, H-6, H-6' , H-5) , 4.07 (IH, dd, -7₄,₅ 2.4, J_4/3 8.7 Hz, H-4), 4.17 (IH, dd, J_3j2 6.0, J_3li 8.7 Hz, H-3), 4.55 (IH, dd, J_2ι± 5.1, J-₂,₃ 6.0 Hz, H-2) , 4.69 (IH, d, J_ll2 5.1 Hz, H-l) .

Example 10 W,JV-Dihexyl-S- (β-D-galactofuranosyl) sulf onamide (5, R¹ = R²

= C₅Hι₃) : Yield: 78%. JR_f 0.24 (EtOAc) . ^XH NMR (300 MHz,

CD₃OD) : δ.0.92 (6H, t, 2 x CH₃) , 1.27-1.40 (12H, m, 6 x CH₂) , 1.53-1.66 (4H, m, 2 x CH₂) , 3.16-3.36 (4H, m, 2 x

CH₂) , 3.55-3.73 (3H, m, H-6, H-6' , H-5) , 4.05 (IH, dd, J_{4 5}

2.4, <J₄,₃ 8.7 Hz, H-4) , 4.15 (IH, dd, ^" ₃,₂ 6.3, J_3/4 8.7 Hz,

H-3) , 4.52 (IH, dd, J_2ιl 5.1, J_2/3 6.3 Hz, H-2) , 4.66 (IH, d, ιTι,₂ 5.1 Hz, H-l) .

Example 11

-V,iV-Dioctyl-S- (β-D-galactofuranosyl) sulf onamide (5, R¹ = R²

= C₈H₁₇) : Yield: 75%. R_£ 0.58 (EtOAc) . ¹H NMR (300 MHz, CD₃OD) : δ 4.58 (d, 1 H, J 5.2 Hz, H-l) , 4.44 (dd, 1 H, J_2ι3

6.1, «7₂,ι 5.2 Hz, H-2) , 4.06 (dd, 1 H, J₃ 8.7, ι7₃,₂ 6.1 Hz,

H-3) , 3.96 (dd, 1 H, J_irS 2.4, J^" _4/3 8.7 Hz, H-4) , 3.62 (m, 1

H, H-5) , 3.52 (m, 2 H, H-6 and H-6') , 3.20 ( , 4 H,

N(CH₂)₂) , 1.52 (m, 4 H, 2 x CH₂, dioctyl chain) , 1.23 (m, 20 H, 10 x CH₂, dioctyl chain) , 0.82 (app t, 6 H, J^" 6.5, J

6.9 Hz, 2 x CH₃) ; LRMS (ESI) : ^m/_z 490 [ (M + Na) ⁺ 100%] ;

Anal. Calcd for C₂₂H₄₅N0₇S .¹/₂ H₂0: C, 55.43; H, 9.73; N,

2.94. Found: C, 55.75; H, 10.07; N, 2.80.

Example 12 iV,JV-Didecyl-S- (β-D-galactofuranosyl) sulfonamide (5, R¹ = R²

= CιoH₂ι) : Yield: 89%. J _f 0.31 (EtOAc) . ²H NMR (300 MHz,

CD₃OD) : δ.0.91 (6H, t, 2 x CH₃) , 1.26-1.38 (28H, m, 14 x CH₂) , 1.54-1.66 (4H, m, 2 x CH₂) , 3.21-3.36 (4H, m, 2 x

CH₂) , 3.55-3.73 (3H, , H-6, H-6' , H-5) , 4.05 (IH, dd, J_iι5

2.4, J₄,₃ 8.7 Hz, H-4) , 4.15 (IH, dd, J₃,₂ 6.3, J_{3 4} 9.0 Hz,

H-3) , 4.53 (IH, dd, J_2>1 5.4, J₂,₃ 6.0 Hz, H-2) , 4.67 (IH, d, J^"ι, ₂ 5.1 Hz, H-l) .

Example 13

N,N-Dibenzyl-S- (β-D-galactofuranosyl) sulfonamide (5, R¹ =

R² = CH₂Ph) : Yield: 76%. R 0.42 (EtOAc). ^XH NMR (300 MHz, CD₃OD) : δ 7.17-7.32 (m, 10 H, N(CH₂Ph)₂), 4.75 (d, 1 H, J 5.0 Hz, H-l), 4.64 (m, 1 H, , H-2), 4.47 (d, 2 H, J 15.4 Hz, 1 x N(CH₂Ph)₂), 4.31 (d, 2 H, J 15.5 Hz, 1 x N(CH₂Ph)₂), 4.15-4.22 (m, 2 H, H-3 and H-4), 3.73 (app dt, 1 H, J 2.0, J 6.5 Hz, H-5), 3.58-3.63 (m, 2 H, H-6 and H-6'); LRMS (ESI): ^m/_z 446 [ (M + Na) ⁺ 100%]; Anal. Calcd for C₂₀H₂₅NO₇S: C, 56.72; H, 5.95; N, 3.31. Found: C, 56.33; H, 6.01; N, 3.10.

Example 14

N,N-Oi (2-methoxyethoxyethyl) -S- (β-D- galactofuranosyl) sulf onamide (5, R¹ = R² = CH₂CH₂OCH₂CH₂OCH₃) : Yield: 87%. R_f 0.39 (14:5:1

EtOAc /me thanol/H₂0) .* ^XH NMR (300 MHz, D₂0) : δ 3.37 (6H, s, OMe) , 3.49 (IH, m, H-6), 3.50-3.75 (16H, overlapping m, OCH₂) , 3.75 (IH, m, H-6"), 3.82 (IH, m, H-5), 4.08 (IH, dd, ιT₃,₄ 9.0 Hz, ^" ₂,₃ 6.3 Hz, H-4), 4.19 (IH, dd, J₂,₃ 6.3 Hz, ι7₃,₄ 9.0 Hz, H-3) , 4.61 (IH, dd, J_lι2 5.4 Hz, «7₂,₃ 6.6 Hz, H-2), 5.07 (IH, d, J_lι2 5.4 Hz, H-l); LRMS (ESI) : m/z 470.9 [(M + Na)⁺, 100%) .

Example 15 N iV,,N-V--ODii>octyl-S- (β-D-glucofuranosyl) sulfonamide (8, R¹ = R² C₈H₁₇) : Yield: 55%. R_£ 0.05 (1:1 Hexanes/EtOAc) . ^Η NMR (300 MHz, CD₃OD) : δ.0.88 (6H, t, 2 x CH₃) , 1.21-1.37 (20H, m, 10 x CH₂) , 1.50-1.64 (4H, m, 2 x CH₂) , 3.13-3.35 (4H, m, 2 x CH₂) , 3.59 (IH, dd, ι7₆,₅ 5.4, J₆.₆> 11.4 Hz, H- 6) , 3.75 (IH, dd, J₆> ,s 2.7, J ,₆ 11.7 Hz, H-6') , 3.89-3.95 (IH, m, H-5), 3.95-4.10 (2H, , H-3, H-4), 4.47 (IH, app. s, H-2), 4.68 (IH, d, J_lι2 1.8 Hz, H-l) .

Example 16 iV,itf-Dioctyl-S- (2,3,5, 6- tetra-O- acetyl -β-D- glucofuranosyl) sulf inamide (15) (R_x = R₂ = C₈Hι₇) : A solution of W,JV-dioctyl-S- (2, 3 , 5, 6-tetra-O- acetyl-β-D-glucofuranosyl) sulfenamide (6) in CH₂C1₂, will be added dropwise to a stirred and cooled solution of N- chlorosuccinimide in CH₂C1₂. Stirring will be continued for 15-30 minutes. After this time sat. aq. KHC0₃ will be added with stirring. The organic layer will be separated and dried (K₂C0₃) , filtered, and the solvent removed under reduced pressure. The residue will be chromatographed to yield iV,W-dioctyl-S- (2, 3 , 5, 6-tetra-O-acetyl-β-D- glucofuranosyl) sulfinamide (15) .

Example 17

JNT,iV-Dioctyl -S- ( β -D-glucofuranosyl ) sulf inamide ( 16 ) (R_x = R₂

= C₈Hι₇) : To a solution of W,iV-dioσtyl-S- (2 , 3 , 5, 6-tetra-O- acetyl-β-D-glucofuranosyl) sulfinamide (15) in dry MeOH will be added one equivalent of NaOMe (IM solution in dry MeOH) . The reaction will be stirred at room temperature for 2 h under N₂. After this time the solution is to be neutralised with Amberlite IR 120 (H⁺) resin, filtered, and the solvent removed under reduced pressure. The residue will be chromatographed to yield N,N-dioctyl-S- (β-D- glucofuranosyl) sulfinamide (16) .

Biological Data

Example 18 Inhibition of Staphylococcus aureus by compounds (5) and (8) where R¹ = R² = C₈H₁₇ is described in Table 1. The biological data were determined by Minimum Inhibitory Concentration (MIC) Assay. Each compound was added to 4 ml of LB broth at a starting concentration of 256 μg/ml. Serial dilutions were then made, 1 in 2 at each step, ending with 2 μg/ml. 5 μL of a saturated culture was added to each serial dilution which were then incubated at 37 °C with shaking for 18 to 20 hours. The MIC₈₀ was then determined as the concentration in which there was 80% or greater reduction in growth as compared to the control.

Table 1

Example 19 Inhibition of various bacteria by compounds (5) and (8) where R¹ = R² = C₈H₁₇ is described in Table 2. The biological data were determined by a Zone Inhibition Assay method. Compounds were tested by spotting 100 μg of compound as a solution in methanol onto a sterile filter disc placed on a lawn of bacteria on the surface of an LB agar plate. After incubation at 37 °C overnight, the zone of inhibition was measured using an arbitrary scale: +++ = relatively large zone of inhibition, - = no zone of inhibition.

Table 2

Industrial Applicability The compounds of general formula (I) are useful as pharmaceutical agents, particularly anti-microbial agents . References The disclosure of the following documents is incorporated herein by reference: von Itzstein, M.; u, W-Y.; Kok, G.B.; Pegg,

M.S.; Dyason, J.C.; Jin, B.; Phan, T.V.; S ythe, M.L.; White, H.F.; Oliver, S.W.; Colman, P.M.; Varghese, J.N.; Ryan, D.M.; Woods, J.M.; Bethell, R.C.; Hotham, V.J.; Cameron, J.M.; Penn, CR. Nature 1993, 363 , 418-423. Kok, G.B.; Campbell, M.; Mackey, B.; von

Itzstein, M. J. Chem. Soc , Perkin Trans . 1 1996, 2811- 2815. Fazli, A.; Bradley, S.J.; Kiefel, M.J.; Jolley, C; Holmes, I.H.; von Itzstein, M. J^". Med. Chem. 2001, 44 , 3292-3301. Owen, D. J.; von Itzstein, M. Carbohyr . Res . 2000, 328 , 287-292. Marino, C; Marino, K.; Miletti, L. C; Alves, M. J. M.; Colli, W. ; de Lederkremer, R. M. Glycobiology 1998, 8 , 901-904. Miletti, L. C; Marino, C; Marino, K.; de Lederkremer, R. M. ; Colli, W. ; Alves, M. J. M. Carbohydr. Res . 1999, 320 , 176-182. Zhang, Q.; Liu, H. J. Am. Chem. Soc . 2001, 123 , 6756-6766. Brimacombe, J.; Gent, P.; Stacey, M. J^". Chem. Soc . Org. 1968, 567-569. Brimacombe, J.; Da'aboul, I.; Tucker, L. J^". Chem. Soc. Org. 1971, 3762. Le ieux, R. U.; Stick, R. V. Aust . J. Chem.

1975, 28 , 1799-1801. de Lederkremer R. M.; Cirelli, A.; Sznaidman, M. L. Carbohydr. Res . 1986, 146, 233-240. Shin, J.; Perlin, A. Carbohydr. Res . 1979, 76 , 165-176. de Lederkremer R. M.; Cicero, D.; Varela, O. Tetrahedron 1990, 46, 1131-1144. de Lederkremer, R. M. ; Marino, K.; Marino, C. Anal. Biochem. 2002, 301 , 325-328. Pathak, A. K.; Pathak, V.; Suling, W. J.; Gurcha, S. S.; Morehouse, C. B.; Besra, G. S.; Maddry, J. A.; Reynolds, R. C. Bioorgr. Med. Chem. 2002, 10 , 923-928. Ernst, B.; Hart, G. W. ; Sinay, P. (Eds), Carbohydrates in Chemistry and Biology, Wiley-VCH, Weinhei , 2000, Vols 1 - 4. Chapleur, Y. Carbohydrate Mimics , Wiley-VCH, Weinheim, 1998. Lillelund, V.H.; Jensen, H.H.; Liang, X.; Bols, M. Chem. Rev. 2002, 102 , 515-553. Craine, L.; Raban, M. Chem..Rev. 1989, 89 , 589- 712. Glass, R.S.; Swedo, R.J. Synthesis 1977, 798-

800. Haake, M. ; Gebbing, H.; Benack, H. Synthesis 1979, 97. Koval¹, I.V. Russ . Chem. Rev. 1996, 65 , 421-440 von Itzstein, L.M.; Coppel, R.L.; Davis, C.B.;

Thomson, R.J.; Owen, D.J. An antimicrobial agent . WO 03/070715, 2003. Illyes, T.-Z.; Molnar-Gabor , D . ; Szilagyi, L. Carbohydr. Res . 2004, 339 , 1561-1564.

Claims

Claims :

1. A compound of general formula (I) :

wherein Ri and R₂ are independently selected from the group consisting of hydrogen, optionally substituted alkyl which may be interrupted by one or more heteroatoms or functional groups selected from the group consisting of O, S, -N=, NR₇ and - (Y) _mC= (Z) (T) _n- , optionally substituted alkenyl which may be interrupted by one or more heteroatoms or functional groups selected from the group consisting of O, S, -N=, NR₇ and - (Y) _mC= (Z) (T) _n- , optionally substituted aralkyl which may be interrupted within the alkyl moiety by one or more heteroatoms or functional groups selected from the group consisting of O, S, -N=, NR₇ and - (Y) _mC= (Z) (T) _n- , optionally substituted heterocyclic, optionally substituted aryl, optionally substituted acyl and a carbohydrate moiety; or Ri and R₂ together with the nitrogen atom from which they depend form a saturated or unsaturated, optionally substituted heterocyclic group which may include additional heteroatoms selected from the group consisting of O, N and S; A is selected from the group consisting of O, S, SO, S0₂, Se, Te, NR₈, CR₉R'₉, N->0 and C (O) ; Xi is selected from the group consisting of OR₃, SR₃, NR₃R'₃, hydrogen, halogen, - (Y)_mC= (Z) (T) _nR₃, -

N(C=(Z) (T)_nR₃)₂, N₃, CN, OCN, SCN, OS0₃R₃, OS0₂R₃, OP0₃R₃R'₃, OP0₂R₃R'₃, S(0)R₃, S(0)₂R₃, S(0)₂0R₃, P0₃R₃R'₃, NR₃NR'₃R"₃, SNR₃R'₃, NR₃SR'₃, SSR₃ and R₃, or is an oxo group, =S, =NOR₃ or =CR₃R' ₃ and i ' is absent, or X_x is C=(Z) and R₂ is bonded thereto so as to form a cyclic moiety - C=(Z)NR_!S(0)_p-; X₂ is selected from the group consisting of 0R₄, SR₄, NR₄R'₄, hydrogen, halogen, - (Y)_mC= (Z) (T) _nR₄, - N(C=(Z) (T)_nR₄)₂, N₃, CN, OCN, SCN, OS0₃R₄, OS0₂R₄, OP0₃R₄R'₄ OP0₂R₄R'₄, S(0)R₄, S(0)₂R₄, S(0)₂OR₄, P0₃R₄R'₄, NR₄NR'₄R''₄, SNR₄R'₄, NR₄SR'₄, SSR₄ and R₄, or is an oxo group, =S, =NOR₄ or =CR₄R' ₄ and X₂ ' is absent; X₃ and X₃ ' are independently selected from the group consisting of OR₅, SR₅, NR₅R' , hydrogen, halogen, - (Y)_mC=(Z) (T)_nR₅, -N(C=(Z) (T)_nR₅)₂, N₃, CN, OCN, SCN, OS0₃R₅, OS0₂R₅, OP0₃R₅R' 5/ OP0₂R₅R'₅ S(0)R₅, S(0)₂R₅, S(0)₂OR₅, P0₃R₅R'₅, NR₅NR'₅R''5, SNR₅R'₅/ NR₅SR'₅, SSR₅ and R₅, or X₃ is an oxo group, =S, =NOR₅ or =CR_SR' ₅ and X₃ ' is absent; X₄ is selected from the group consisting of OR₅,

SR₆, NR₆R'₆, hydrogen, halogen, - (Y) _mC= (Z) (T) _nR₆, - N(C=(Z) (T)_nR₅)₂, N₃, CN, OCN, SCN, OS0₃R₆, OS0₂R₆, OP0₃R₆R' _s, OP0₂R₆R'₆, S(0)R₆, S(0)₂R₆, S(0)₂OR₆, P0₃R₆R'₆, NR_eNR'₆R''₆, SNRgR's, NR₆SR'_6/ SSR_S and R₆, or is an oxo group, =S, =N0R₆ or =CR_SR' ₆ and X₄ ' is absent; X₅ is selected from the group consisting of hydrogen, CN, -C=(Z) (T)_nR_u, S(0)R_11; S(0)₂Rn, S(0)₂ORn, P0₃RiiR'n, optionally substituted alkyl, optionally substituted alkaryl, optionally substituted aryl, optionally substituted aralkyl, and optionally substituted acyl; Xi', X₂ ' , X₄ ' and X₅ ' are the same or different and are selected from the group consisting of hydrogen, CN, optionally substituted alkyl, optionally substituted alkaryl, optionally substituted aryl, optionally substituted aralkyl, and optionally substituted acyl; or one of X_x and X_2/ X₂ and X₅ ' , X₅ ' and A when A contains a carbon or nitrogen atom, X₅ and A when A contains a carbon or nitrogen atom, and X₅ and Xi together constitute a double bond, or X₅ ' and X₄ or X₃ and X together constitute a double bond, or Ri and Xi, R₂ and Xi, Ri and X₂, R₂ and X₂, Ri and X₅, R₂ and X₅, Ri and X₅' , R and X₅' , Xx and X₂, X₂ and X₃ , X₂ and X₄, X₃ and X₄, Xj_. and Xi' , X₂ and X₂' , X₃ and X₃' or X₄ and X₄' together form part of a ring structure which optionally includes at least one heteroatom selected from O, S and N and is optionally substituted; m and n are independently zero or one and Y, Z and T are independently selected from the group consisting of O, S, and NRio p is 1 or 2 q is 0 or 1; R₃ , R' ₃ , R ₃, R₄ , R , R' '₄, R5, R 5, R 5, Rε , R 6

R''6r ₇/ Rs R9, R'9/ io/ R11 and R' n are the same or different and are selected from the group consisting of hydrogen, optionally substituted alkyl which may be interrupted by one or more heteroatoms or functional groups selected from the group consisting of O, S, -N=, NR and -(Y)_mC=(Z) (T)_n-, optionally substituted alkenyl which may be interrupted by one or more heteroatoms or functional groups selected from the group consisting of O, S, -N=, NR₇ and - (Y) _mC= (Z) (T) _n- , optionally substituted aryl, optionally substituted heterocyclic, optionally substituted aralkyl which may be interrupted within the alkyl moiety by one or more heteroatoms or functional groups selected from the group consisting of 0, S, -N=, NR₇ and -(Y)_mC=(Z) (T)_n-, optionally substituted acyl and a carbohydrate moiety; with the proviso that at least two of X_{l r} X₂, X₃ and X₄ are other than hydrogen or a group linked to the ring through a carbon-carbon bond; or a pharmaceutically acceptable salt thereof.

2. A compound as claimed in claim 1 wherein one or both of Ri and R₂ is alkyl.

3. A compound as claimed in claim 2 wherein one or both of Ri and R₂ is C₄.₃₀ alkyl.

4. A compound as claimed in claim 3 wherein one or both of Ri and R₂ is C_S-ι₂ alkyl.

5. A compound as claimed in claim 4 wherein one or both of Ri and R₂ is C₈_₁₀ alkyl.

6. A compound as claimed in claim 1 wherein one or both or Ri and R₂ is aralkyl.

7. A compound as claimed in claim 6 wherein one or both Ri and R₂ is (CH₂)_rPh where Ph is phenyl and r is an integer in the range 1 to 12 inclusive.

8. A compound as claimed in claim 1 wherein one or both of Ri and R₂ is alkyl interrupted by one or more heteroatoms or functional groups selected from the group consisting of O, S, -N=, NR₇ , and - (Y)_mC= (Z) (T) _n.

9. A compound as claimed in claim 8 wherein one or both of Ri and R₂ is alkyl interrupted by one or more oxygen atoms .

10. A compound as claimed in claim 9 wherein one or both of Ri and R₂ is CH₃ (CH₂) _xO (CH₂)_yO (CH₂) _z wherein x is an integer in the range 0 to 12 inclusive and y and z are independently integers in the range 1 to 12 inclusive.

11. A compound as claimed in claim 1 wherein one or both of Ri and R is alkenyl.

12. A compound as claimed in claim 1 wherein Ri and R₂ together with the nitrogen atom from which they depend form a saturated or unsaturated heterocyclic group.

13. A compound as claimed in claim 1 wherein R_x and R₂ together with the nitrogen atom from which they depend form a lactam or cyclic imide.

14. A compound as claimed in any one of claims 1 to 13 wherein q is 1.

15. A compound as claimed in any one of claims 1 to 13 wherein q is 0.

16. A compound as claimed in any one of claims 1 to 15 wherein A is selected from the group consisting of 0, S and NR₈.

17. A compound as claimed in claim 16 wherein A is O.

18. A compound as claimed in any one of claims 1 to 17 wherein X_x is 0R₃.

19. A compound as claimed in claim 18 wherein R₃ is hydrogen or optionally substituted acyl.

20. A compound as claimed in any one of claims 1 to 19 wherein X₂ is OR₄.

21. A compound as claimed in claim 20 wherein R₄ is hydrogen or optionally substituted acyl .

22. A compound as claimed in any one of claims 1 to 21 wherein X₃ is OR₅.

23. A compound as claimed in claim 22 wherein R₅ is hydrogen or optionally substituted acyl.

24. A compound as claimed in any one of claims 1 to 14 and 16 to 23 wherein X₄ is OR_s.

25. A compound as claimed in claim 24 wherein R₆ is hydrogen or optionally substituted acyl.

26. A compound as claimed in any one of claims 1 to 25 wherein p is 1.

27. A compound as claimed in any one of claims 1 to 25 wherein p is 2.

28. A compound selected from the group consisting of: N, N-dibutyl-S- (2,3,5, 6-tetra-O-benzoyl-β-D- galactofuranosyl) sulfonamide N, N-dihexyl-S- (2,3,5, 6-tetra-O-acetyl-β-D- galactofuranosyl) sulfonamide N, N-dioctyl-S- (2,3,5, 6-tetra-O-benzoyl-β-D- galactofuranosyl) sulfonamide jV,I-didecyl-S- (2,3,5, 6-tetra-O-acetyl-β-D- galactofuranosyl) sulfonamide W,N-dibenzyl-S- (2 , 3 , 5 , 6-tetra-O-benzoyl-β-D- galactofuranosyl) sulfonamide N, N-di (2-methoxyethoxyethyl) -S- (2 , 3, 5, 6-tetra-O- acetyl-β-D-galactofuranosyl) sulfonamide N, N-dioctyl-S- (2,3,5, 6-tetra-O-acetyl-β-D- glucofuranosyl) sul onamide 2,N-dioctyl-S-(2,3-di-0-acetyl-5-0-[fcerfc- butyldiphenylsilyl] - α-D-arabinofuranosyl) sulfonamide N, N- d±b tyl-S- (β-D-galactofuranosyl) sulfonamide N, N-dihexyl-S- (β-D-galactofuranosyl) sulfonamide N, N-dioctyl-S- (β-D-galactofuranosyl) sulfonamide N, iV-didecyl-S- (β-D-galactofuranosyl) sulfonamide N, ΪV-dibenzyl-S- (β-D-galactofuranosyl) sulfonamide N, N-d± (2-methoxyethoxyethyl) -S- (β-D- galactofuranosyl) sulfonamide N,N-dioctyl-S- (β-D-glucofuranosyl) sulfonamide 29. A method of preparation of a compound of general formula (I)

comprising reacting a compound of general formula (II) :

wherein R_x , R₂ , A, p , q, X_{l 7} X_x ' , X₂ , X₂ ' , X₃ , X₃ ' , X₄ , X₄ ' , X₅ and X₅ ' are as def ined above ; with an oxidising agent. 30. A method for the treatment of a microbial infection comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound of general formula (I) as claimed in any one of claims 1 to 28. 31. The use of a compound of general formula (I) as claimed in any one of claims 1 to 28 in the manufacture of a medicament for use in the treatment of a microbial infection. 32. A pharmaceutical composition comprising a compound of general formula (I) as claimed in any one of claims 1 to 28 and a pharmaceutically acceptable carrier. 33. A method of killing a microorganism, comprising exposing said microorganism to a compound of general formula (I) as claimed in any one of claims 1 to 28.