New class of quaternary ammonium salts, derivatives of methyl D-glucopyranosides

Reactions of two aromatic and two aliphatic amines with methyl 6-O-p-toluenesulfonyl-alpha-D-glucopyranoside or methyl 6-O-p-toluenesulfonyl-beta-D-glucopyranoside were performed on a micro-scale. The synthesis and preparative isolation methods have been developed for quaternary N-(methyl 2,3,4-tri-O-acetyl-6-deoxy-alpha- and -beta-D-glucopyranoside-6-yl)ammonium salts derived from three amines: trimethylamine, 2-methylpyridine, and pyridine. The reaction products were examined with 1H, 13C NMR spectroscopy. N-(Methyl 2,3,4-tri-O-acetyl-6-deoxy-beta-d-glucopyranoside-6-yl)trimethylammonium tosylate was additionally analyzed with X-ray crystallography.     

Acetylated methyl glucopyranuronate trichloroacetimidate as a glycosyl donor for efficient synthesis of disaccharides

Allyl (methyl 2,3,4-tri-O-acetyl-beta-D-glucopyranosyl uronate)-(1-->3)-4,6-O-benzylidene-2-deoxy-2-phthalimido-beta-D-glucopyranoside (4) and benzyl (methyl 2,3,4-tri-O-acetyl-beta-D-glucopyranosyl uronate)-(1-->3)-4,6-O-benzylidene-2-deoxy-2-phthalimido-beta-D-glucopyranoside (5) have been efficiently synthesized by coupling allyl 4,6-O-benzylidene-2-deoxy-2-phthalimido-beta-D-glucopyranoside (2) or benzyl 4,6-O-benzylidene-2-deoxy-2-phthalimido-beta-D-glucopyranoside (3) with methyl (2,3,4-tri-O-acetyl-1-O-trichloroacetimidoyl)-alpha-D-glucopyranuronate (1), respectively, using trimethylsilyl triflate as promoter.     

Synthesis of methyl 6'-deoxy-6'-fluoro-alpha-isomaltoside and of the corresponding trisaccharide

Methyl 6-O-(6-O-acetyl-2,3,4-tri-O-benzyl-alpha-D-glucopyranosyl)-2,3,4-tri- O-benzyl-alpha-D-glucopyranoside (5) was formed with high stereoselectivity when the condensation of methyl 2,3,4-tri-O-benzyl-alpha-D-glucopyranosyl (1) with 6-O-acetyl-2,3,4-tri-O-benzyl-alpha-D-glucopyranosyl chloride in ether was promoted with silver perchlorate in the presence of 2,4,6-trimethylpyridine. O-Deacetylation of 5, followed by treatment of the formed 6, containing only HO-6' unsubstituted, with diethylaminosulfur trifluoride (DAST) or dimethylaminosulfur trifluoride (methyl DAST) gave the per-O-benzyl derivative (9) of methyl 6'-deoxy-6'-fluoro-alpha-isomaltoside. Compound 9 was also obtained by condensation of 1 with 2,3,4-tri-O-benzyl-6-deoxy-6-fluoro-beta-D-glucopyranosyl fluoride (4) in the presence of silver perchlorate and anhydrous stannous chloride. The fully benzylated methyl alpha-glycoside (15) of 6-deoxy-6-fluoro-isomaltotriose, was obtained by condensation of 6 with 4. Hydrogenolysis of 9 and 15 gave the methyl alpha-glycosides of isomaltose and isomaltotriose fluorinated at C-6 of their (nonreducing) D-glucosyl group. Fluoride-ion displacements involving DAST and methyl DAST gave practically identical results, but mixtures arising from reactions involving the latter reagent were lighter-colored and easier to resolve by chromatography. The isolation of methyl alpha-glycosides of 6'-deoxy-6'-fluorogentiobiose and of 6'-O-(6-deoxy-6-fluoro-beta-D-glucopyranosyl) isomaltose is also described.     

Efficient chemical synthesis of methyl beta-glycosides of beta-(1----6)-linked D-galacto-oligosaccharides by a stepwise and a blockwise approach

Bromoacetylation of methyl 2,3,4-tri-O-benzoyl-beta-D-galactopyranoside (1) followed by cleavage of the methoxyl group from the resulting 6-O-bromoacetyl derivative 2 with 1,1-dichloromethyl methyl ether gave 2,3,4-tri-O-benzoyl-6-O-bromoacetyl-alpha-D-galactopyranosyl chloride (3). Reaction of 3 with 1, promoted by silver trifluoromethanesulfonate, afforded methyl O-(2,3,4-tri-O-benzoyl-6-O-bromoacetyl-beta-D-galactopyranosyl)-(1----6) -2,3,4-tri-O-benzoyl-beta-D-galactopyranoside (12), bearing at O-6 of its non-reducing end-group the selectively removable bromoacetyl group. This was O-debromoacetylated and the disaccharide nucleophile 15 formed was again treated with 3, to give the analogous trisaccharide 18. This sequence of reactions was repeated to afford the analogous tetrasaccharide 20, showing the feasibility of stepwise construction of the title oligosaccharides. Similar reactions of 3 with 1,2,3,4-tetra-O-benzoyl-alpha- (7) and beta-D-galactopyranose (5) gave, respectively, O-(2,3,4-tri-O-benzoyl-6-O-bromoacetyl-beta-D-galactopyranosyl)-(1----6) -1,2,3,4-tetra-O-benzoyl-alpha- (14) and beta-D-galactopyranose (13). These could be separately converted into the same glycosyl halide, namely, alpha-(2,3,4-tri-O-benzoyl-6-O-bromoacetyl-beta-D-galactopyranosyl)-(1-- --6)-2,3,4-tri-O-benzoyl-alpha-D-galactopyranosyl chloride (16), by cleavage with 1,1-dichloromethyl methyl ether. The chloride 16 was treated with tri- and tetra-saccharide nucleophiles analogous to 15 to give, respectively, the corresponding pentasaccharide 23 and the hexasaccharide 25, demonstrating the possibility of the blockwise construction of higher beta-(1----6)-linked D-galacto-oligosaccharides. The disaccharide 12 was also obtained by the reaction of 1,2,3,4-tetra-O-benzoyl-6-O-bromoacetyl-beta-D-galactopryanose (6) with 1 in the presence of trimethylsilyl trifluoromethane-sulfonate. Similarly, the trisaccharide 18 and the tetrasaccharide 20 were obtained by the treatment of 13, respectively, with 1 and 15, showing that, as with their 1-O-acetyl counterparts, beta-1-benzoates of saccharides bearing at O-2 a group capable of neighboring-group participation can act under these conditions as glycosyl donors. Crystalline methyl beta-glycosides of (1----6)-beta-D-galacto-tetraose (22), -pentaose (24) and -hexaose (27) have been obtained for the first time, by deacylation (Zemplén) of their fully protected precursors.     

Facile synthesis of the heptasaccharide repeating unit of O-deacetylated GXM of C. neoformans serotype B

A heptasaccharide, beta-D-Xylp-(1-->2)-alpha-D-Manp-(1-->3)-[beta-D-Xylp-(1-->2)]-alpha-D-Manp-(1-->3)-[beta-D-GlcpA-(1-->2)][beta-D-Xylp-(1-->4)]-alpha-D-Manp, the repeating unit of the exopolysaccharide from Cryptococcus neoformans serovar B, was synthesized as its methyl glycoside. Thus 2,3,4-tri-O-benzoyl-beta-D-xylopyranosyl-(1-->2)-3,4,6-tri-O-benzoyl-alpha-d-mannopyranosyl trichloroacetimidate (7) and allyl 2,3,4-tri-O-benzoyl-beta-D-xylopyranosyl-(1-->2)-4,6-di-O-benzoyl-alpha-D-mannopyranoside (8), readily obtained from the corresponding monosaccharide derivatives via simple transformation, were coupled to give a (1-->3)-linked tetrasaccharide 9. Deallylation of 9 followed by trichloroacetimidate formation produced the tetrasaccharide donor 11. Condensation of methyl 2,3,4-tri-O-benzoyl-beta-d-xylopyranosyl-(1-->4)-2-O-acetyl-6-O-benzoyl-alpha-D-mannopyranoside (18) with 11 followed by selective deacetylation yielded hexasaccharide acceptor 20. Coupling of 20 with methyl 2,3,4-tri-O-acetyl-alpha-D-glucopyranosyluronate bromide (21) and subsequent deprotection furnished the target heptaoside. A hexasaccharide fragment, alpha-D-Manp-(1-->3)-[beta-D-Xylp-(1-->2)]-alpha-D-Manp-(1-->3)-[beta-D-GlcpA-(1-->2)][beta-D-Xylp-(1-->4)]-alpha-D-Manp, was also similarly synthesized as its methyl glycoside.     

Synthesis of disaccharide fragments of dermatan sulfate

Condensation of crystalline methyl 2-azido-4,6-O-benzylidene-2-deoxy-beta-D-galactopyranoside with methyl (2,3,4-tri-O-acetyl-alpha-L-idopyranosyl bromide)uronate in dichloromethane, in the presence of silver triflate and molecular sieve, provided 54% of methyl 2-azido-4,6-O-benzylidene-2-deoxy-3-O-(methyl 2,3,4-tri-O-acetyl-alpha-L-idopyranosyluronate)-beta-D-galactopyranoside . The use of methyl (2,3,4-tri-O-acetyl-alpha-L-idopyranosyl trichloroacetimidate)uronate as glycosyl donor, in the presence of trimethylsilyl triflate, improved the yield to 68%. Regioselective opening of the benzylidene group with sodium cyanoborohydride followed successively by O-sulfation with the sulfur trioxide-trimethylamine complex, saponification, catalytic hydrogenolysis and selective N-acetylation gave the disodium salt of methyl 2-acetamido-2-deoxy-3-O-(alpha-L-idopyranosyluronic acid)-4-O-sulfo-beta-D-galactopyranoside. Condensation of methyl 2-azido-4,6-O-benzylidene-2-deoxy-beta-D-galactopyranoside with methyl (2,3,4-tri-O-acetyl-alpha-D-glucopyranosyl bromide)uronate in dichloromethane, in the presence of silver triflate and molecular sieve, gave methyl 2-azido-4,6-O-benzylidene-2-deoxy-3-O-(methyl 2,3,4-tri-O-acetyl-beta-D-glucopyranosyluronate)-beta-D-galactopryano side in 85% yield. The sequence already described then gave the disodium salt of methyl 2-acetamido-2-deoxy-3-O-(beta-D-glucopyranosyluronic acid)-4-O-sulfo-beta-D-galactopyranoside.     

Synthesis of methyl O-(3-deoxy-3-fluoro-β-d-galactopyranosyl)-(1→6)-β-d-galactopyranoside and methyl O-(3-deoxy-3-fluoro-β-d-galactopyranosyl)-(1→6)-O-β-d-galactopyranosyl-(1→6)-β-d-galactopyranoside

Condensation of 2,4,6-tri-O-acetyl-3-deoxy-3-fluoro-α-d-galactopyranosyl bromide (3) with methyl 2,3,4-tri-O-acetyl-β-d-galactopyranoside (4) gave a fully acetylated (1→6)-β-d-galactobiose fluorinated at the 3′-position which was deacetylated to give the title disaccharide. The corresponding trisaccharide was obtained by reaction of 4 with 2,3,4-tri-O-acetyl-6-O-chloroacetyl-α-d-galactopyranosyl bromide (5), dechloroacetylation of the formed methyl O-(2,3,4-tri-O-acetyl-6-O-chloroacetyl-β-d-galactopyranosyl)-(1→6)- 2,3,4-tri-O-acetyl-β-d-galactopyranoside to give methyl O-(2,3,4-tri-O-acetyl-β-d-galactopyranosyl)-(1→6)-2,3,4-tri-O-acetyl-β-d-galactopyranoside (14), condensation with 3, and deacetylation. Dechloroacetylation of methyl O-(2,3,4-tri-O-acetyl-6-O-chloroacetyl-β-d-galactopyranosyl)-(1→6)-O-(2,3,4-tri-O-acetyl- β-d-galactopyranosyl)-(1→6)-2,3,4-tri-O-acetyl-β-d-galactopyranoside, obtained by condensation of disaccharide 14 with bromide 5, was accompanied by extensive acetyl migration giving a mixture of products. These were deacetylated to give, crystalline for the first time, the methyl β-glycoside of (1→6)-β-d-galactotriose in high yield. The structures of the target compounds were confirmed by 500-MHz, 2D, ¹H- and conventional ¹³C- and ¹⁹F-n.m.r. spectroscopy.     

Synthesis of the two monomethyl esters of the disaccharide 4-O-alpha-D-galacturonosyl-D-galacturonic acid and of precursors for the preparation of higher oligomers methyl uronated in definite sequences.

Methyl (alpha-D-galactopyranosyluronic acid)-(1-->4)-D-galactopyranuronate and methyl alpha-D-galactopyranosyl-uronate-(1-->4)-D-galactopyranuronic acid have been synthesized by coupling methyl (benzyl 2,3-di-O-benzyl-beta-D-galactopyranosid)uronate (3) or benzyl (benzyl 2,3-di-O-benzyl-beta-D-galactopyranosid)uronate (4) with benzyl (phenyl 2,3,4-tri-O-benzyl-1-thio-beta-D-galactopyranosid)uronate and methyl (phenyl 2,3,4-tri-O-benzyl-1-thio-beta-D-galactopyranosid)uronate, respectively, using N-iodosuccinimide and trifluoromethanesulphonic acid as promoters, followed by removal of the benzyl groups. The 4'-OH unprotected dimers benzyl (methyl 2,3-di-O-benzyl-alpha-D-galactopyranosyluronate)-(1-->4)-(benzyl 2,3-di-O-benzyl-beta-D-galactopyranosid)uronate and methyl (benzyl 2,3-di-O-benzyl-alpha-D-galactopyranosyluronate)-(1-->4)-(benzyl 2,3-di-O-benzyl-beta-D-galactopyranosid)uronate were prepared from methyl (phenyl 2,3-di-O-benzyl-1-thio-4-O-trimethylsilyl-beta-D-galactopyranosid) uronate and benzyl (phenyl 2,3-di-O-benzyl-1-thio-4-O-trimethylsilyl-beta-D-galactopyranosid) uronate and acceptors 4 or 3, respectively. These compounds have been designed to serve as precursors for the preparation of higher-membered D-galacturonic acid oligomers methyl esterified in definite positions.     

Synthesis of methyl O-(3-deoxy-3-fluoro-β- -galactopyranosyl)-(1→6)-β- -galactopyranoside and methyl O-(3-deoxy-3-fluoro-β- -galactopyranosyl)-(1→6)-O-β- -galactopyranosyl-(1→6)-β- -galactopyranoside

Condensation of 2,4,6-tri-O-acetyl-3-deoxy-3-fluoro-α- -galactopyranosyl bromide (3) with methyl 2,3,4-tri-O-acetyl-β- -galactopyranoside (4) gave a fully acetylated (1→6)-β- -galactobiose fluorinated at the 3′-position which was deacetylated to give the title disaccharide. The corresponding trisaccharide was obtained by reaction of 4 with 2,3,4-tri-O-acetyl-6-O-chloroacetyl-α- -galactopyranosyl bromide (5), dechloroacetylation of the formed methyl O-(2,3,4-tri-O-acetyl-6-O-chloroacetyl-β- -galactopyranosyl)-(1→6)- 2,3,4-tri-O-acetyl-β- -galactopyranoside to give methyl O-(2,3,4-tri-O-acetyl-β- -galactopyranosyl)-(1→6)-2,3,4-tri-O-acetyl-β- -galactopyranoside (14), condensation with 3, and deacetylation. Dechloroacetylation of methyl O-(2,3,4-tri-O-acetyl-6-O-chloroacetyl-β- -galactopyranosyl)-(1→6)-O-(2,3,4-tri-O-acetyl- β- -galactopyranosyl)-(1→6)-2,3,4-tri-O-acetyl-β- -galactopyranoside, obtained by condensation of disaccharide 14 with bromide 5, was accompanied by extensive acetyl migration giving a mixture of products. These were deacetylated to give, crystalline for the first time, the methyl β-glycoside of (1→6)-β- -galactotriose in high yield. The structures of the target compounds were confirmed by 500-MHz, 2D, ¹H- and conventional ¹³C- and ¹⁹F-n.m.r. spectroscopy.     

Synthesis of an L-rhamnose tetrasaccharide, the common and major structure of the repeating unit of the O-antigenic polysaccharide of a strain of Klebsiella pneumoniae and Pseudomonas holci.

A tetrasaccharide, alpha-L-Rhap-(1-->3)-alpha-L-Rhap-(1-->2)-alpha-L-Rhap-(1-->2)-L-Rhap, the common and major structure of the repeating unit of the O-antigenic polysaccharide of a strain of Klebsiella pneumoniae and Pseudomonas holci was synthesized as its methyl and octyl glycosides. Selective 3-O-glycosylation of allyl alpha-L-rhamnopyranoside with 2,3,4-tri-O-acetyl-alpha-L-rhamnopyranosyl trichloroacetimidate gave allyl 2,3,4-tri-O-acetyl-alpha-L-rhamnopyranosyl-(1-->3)-alpha-L-rhamnopyranoside (3). Benzoylation, deallylation, and trichloroacetimidation afforded 2,3,4-tri-O-acetyl-alpha-L-rhamnopyranosyl-(1-->3)-2,4-di-O-benzoyl-alpha-L-rhamnopyranosyl trichloroacetimidate (6). Self condensation of 3,4-di-O-benzoyl-beta-L-rhamnopyranose 1,2-methyl orthoester or 1,2-octyl orthoester gave methyl or octyl 2-O-acetyl-3,4-di-O-benzoyl-alpha-L-rhamnopyranosyl-(1-->2)-3,4-di-O-benzoyl-alpha-L-rhamnopyranoside (16 or 17), and subsequent selective deacetylation gave the disaccharide acceptor (18 or 19). Coupling of 6 with 18 (or 19), followed by deacylation in ammonia-saturated methanol, produced the target tetrasacharide.     

Efficient synthesis of a heptasaccharide,the repeating unit of the O-chain lipopolysaccharide produced by Xanthomonas campestris strain 642

alpha-L-Rhap-(1-->3)-alpha-L-Rhap-(1-->2)-alpha-L-Rhap-(1-->3)-[beta-D-Xylp-(1-->2)-][beta-D-Xylp-(1-->4)-]alpha-L-Rhap-(1-->3)-alpha-L-Rhap, the repeating unit of the O-chain lipopolysaccharide produced by Xanthomonas campestris strain 642 was synthesized as its methyl glycoside via 3-O-selective glycosylation of methyl alpha-L-rhamnopyranosyl-(1-->3)-2,4-di-O-benzoyl-alpha-L-rhamnopyranoside (9) with 2,3,4-tri-O-benzoyl-alpha-L-rhamnopyranosyl-(1-->3)-2,4-di-O-benzoyl-alpha-L-rhamnopyranosyl-(1-->2)-3,4-di-O-benzoyl-alpha-L-rhamnopyranosyl trichloroacetimidate (8), followed by dixylosylation with 2,3,4-tri-O-benzoyl-alpha,beta-D-xylopyranosyl trichloroacetimidate (12) and subsequent deacylation.     

Artificial carbohydrate antigens: a block synthesis of a linear, tetrasaccharide repeating-unit of the Shigella flexneri variant Y polysaccharide

Glycosylation of methyl 2,4-di-O-benzoyl-alpha-L-rhamnopyranoside with 2,3,4-tri-O-acetyl-alpha-L-rhamnopyranosyl bromide gave methyl 2,4-di-O-benzoyl-3-O-(2,3,4-tri-O-acetyl-alpha-L-rhamnopyranosyl) -alpha-L-rhamnopyranoside (4) in 93% yield. Conversion of 4 into the corresponding glycosyl bromide was accomplished with dibromomethyl methyl ether. Under Koenigs-Knorr conditions, this bromide reacted with 8-(methoxycarbonyl)octyl 2-O-(2-acetamido-4,6-O-benzylidene-2-deoxy-beta-D-glycopyranosyl)- 3,4-di-O- benzyl-alpha-L-rhamnopyranoside, to provide the protected tetrasaccharide in 91% yield. Removal of blocking groups gave 8-(methoxycarbonyl)octyl O-alpha-L-rhamnopyranosyl-(1---- 3)-O-alpha-L-rhamnopyranosyl-(1---- 3)-O-2-acetamido-2-deoxy-beta-D-glucopyranosyl-(1----2)-alpha-L- rhamnopyranoside. Together with previously synthesized tetrasaccharides of the Shigella flexneri Y O-antigen, this oligosaccharide has been used to study the conformation of O-antigens and to assist in the selection of S. flexneri, variant Y, specific monoclonal antibodies.     

Synthesis of the pentasaccharide related to the repeating unit of the antigen from Shigella dysenteriae type 4 in the form of its methyl ester 2-(trimethylsilyl)ethyl glycoside

Starting from D-mannose, D-glucose and L-fucose, the pentasaccharide derivative methyl 2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl-(1-->3)-2-O-acetyl-4,6-O-benzylidene-alpha-D-mannopyranosyl-(1-->3)-2-O-acetyl-6-O-benzyl-4-O-(2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl)-alpha-D-mannopyranosyl-(1-->4)-[2-(trimethylsilyl)ethyl 2,3-di-O-benzyl-beta-D-glucopyranosid]uronate was synthesized. This compound with two alpha-mannopyranosyl units was transformed, via Walden inversion and subsequent deprotection, into the alpha-D-glucosamine-type target compound, namely methyl alpha-L-fucopyranosyl-(1-->3)-2-acetamido-2-deoxy-alpha-D-glucopyranosyl-(1-->3)-2-acetamido-2-deoxy-4-O-(alpha-L-fucopyranosyl)-alpha-D-glucopyranosyl-(1-->4)-[2-(trimethylsilyl)ethyl beta-D-glucopyranosid]uronate which is related to the repeating unit of the O-antigen from Shigella dysenteriae type 4.     

New water soluble flavone and xanthone glycosides from Hypericum canariense L.

The water soluble portion of the aerial parts of Hypericum canariense L. yielded after acetylation the 5,7,3′4′-tetra- and 7,3′4′-triacetates of a new flavonoid 5,7,3′,4′-tetrahydroxy-3-O-β-d-(methyl 2,3,4-triacetoxypyranuronyl)-quercetin, the 3′-acetate of a new flavonoid 3′-hydroxy-5,7,4′-trimethoxy-3-O-β-d-(methyl 2,3,4-triacetoxypyranuronyl)-quercetin, the 3′-acetate and the 3′5′-diacetate of the new flavonoid 5,3′dihydroxy-7,4′-dimethoxy-3-β-d-(methyl 2,3,4-triacetoxypyranuronyl)-quercetin, the xanthone derivative mangiferin 2′,3′,4′,6′-tetraacetate and the latter's new 1,3,6,7′-tetramethoxy, 1,3,6-trimethoxy-4-acetoxy and 1,7-diacetoxy-3,6-dimethoxy analogs.     

Chlorodifluoromethyl-substituted monosaccharide derivatives--radical activation of the carbon-chlorine-bond

The dithionite-mediated addition of BrCF(2)Cl to 3,4-di-O-pivaloyl-D-xylal (1) generated preferably 1-CF(2)Cl-substituted products, that is, (2-bromo-2-deoxy-3,4-di-O-pivaloyl-beta-D-xylopyranosyl)-chlorodifluoromethane and (2-deoxy-3,4-di-O-pivaloyl-beta-D-threo-pentopyranosyl)-chlorodifluoromethane. Selected chlorodifluoromethyl-substituted monosaccharide derivatives were hydrodechlorinated or alkylated at the CF(2)Cl-group using tin reagents under radical reaction conditions. Thus, hydrodechlorinations of (2,3,4-tri-O-acetyl-6-deoxy-alpha-L-galactopyranosyl)-chlorodifluoromethane and of methyl 3,4-di-O-acetyl-2-C-chlorodifluoromethyl-2,6-dideoxy-alpha/beta-L-glucopyranoside are reported using tri-n-butyltin hydride initiated by AIBN. UV-initiated allylations are reported for reactions of (2-deoxy-3,4-di-O-pivaloyl-beta-D-threo-pentopyranosyl)-chlorodifluoromethane, (2,3,4-tri-O-acetyl-6-deoxy-alpha-L-galactopyranosyl)-chlorodifluoromethane, 1,3,4,6-tetra-O-acetyl-2-C-chlorodifluoromethyl-2-deoxy-alpha-D-glucopyranose, 1,3,4,6-tetra-O-acetyl-2-C-chlorodifluoromethyl-2-deoxy-alpha-D-mannopyranose and methyl 3,4-di-O-acetyl-2-C-chlorodifluoromethyl-2-deoxy-alpha/beta-D-rabinopyranoside with allyltri-n-butyltin.     

Synthesis of a hexasaccharide,the repeating unit of O-deacetylated GXM of C. neoformans serotype A

beta-D-GlcpA-(1-->2)-alpha-D-Manp-(1-->3)-[beta-D-Xylp-(1-->2)]-alpha-D-Manp-(1-->3)[-beta-D-Xylp-(1-->2)]-alpha-D-Manp, the repeating unit of the exopolysaccharide from Cryptococcus neoformans serovar A, was synthesized as its allyl glycoside. Thus, 3-O-selective acetylation of allyl 4,6-O-benzylidene-alpha-D-mannopyranoside afforded 2, and subsequent glycosylation of 2 with 2,3,4-tri-O-benzoyl-D-xylopyranosyl trichloroacetimidate furnished the beta-(1-->2)-linked disaccharide 4. Debenzylidenation followed by benzoylation gave allyl 2,3,4-tri-O-benzoyl-beta-D-xylopyranosyl-(1-->2)-3-O-acetyl-4,6-di-O-benzoyl-alpha-D-mannopyranoside (5), and selective 3-O-deacetylation gave the disaccharide acceptor 6. Coupling of 6 with 2-O-acetyl-3,4,6-tri-O-benzoyl-alpha-D-mannopyranosyl trichloroacetimidate yielded the trisaccharide 8, and subsequent deallylation and trichloroacetimidation gave 2,3,4-tri-O-benzoyl-beta-D-xylopyranosyl-(1-->2)-[2-O-acetyl-3,4,6-tri-O-benzoyl-alpha-D-mannopyranosyl-(1-->3)]-4,6-di-O-benzoyl-alpha-D-mannopyranosyl trichloroacetimidate (9). Condensation of the trisaccharide donor 9 with the disaccharide acceptor 6 gave the pentasaccharide 10 whose 2-O-deacetylation gave the acceptor 11. Glycosylation of 11 with methyl 2,3,4-tri-O-acetyl-alpha-D-glucopyranosyluronate trichloroacetimidate and subsequent deprotection gave the target hexasaccharide.     

Synthése,conformation et méthanolyse des chlorures de 2,3,4-tri-O-chlorosulfonyl-β- et α-L-fucopyranosyle

Treatment of α-L-fucose with sulfuryl chloride at low temperature gave mainly 2,3,4-tri-O-chlorosulfonyl-β-L-fucopyranosyl chloride (1) and a small proportion of the α-anomer (2). Both compounds adopt a ¹C₄ chair conformation. Methanolysis of 1 in the presence of silver carbonate and anhydrous calcium sulfate gave methyl 2,3,4-tri-O-chlorosulfonyl-α-L-fucopyranoside (the β-anomer being only present in small proportion), further converted into methyl α-L-fucopyranoside by treatment with a basic resin and a catalytic amount of sodium iodide. Methanolysis of 1 in the presence of sodium iodide gave directly methyl α-L-fucopyranoside, in a more rapid but less stereoselective way. Methanolysis of 2 in the presence of silver carbonate is very slow and gave, after removal of the chlorosulfonyl groups, methyl β-L-fucopyranoside with a rather poor stereoselectivity.     

Stereoselective synthesis of chirally deuterated (S)-D-(6-(2)H(1))glucose

Chirally deuterated (S)-D-(6-(2)H(1))glucose has been prepared in good overall yield from d-(6,6'-(2)H(2))glucose by a short, five-step synthesis from D-(6,6-(2)H(2))glucose utilizing (R)-(+)-Alpine-Borane [(R)-9-[(6,6-dimethylbicyclo[3.1.1]hept-2-yl)methyl]-9-borabicyclo[3.3.1]nonane]. Suitably protected methyl 2,3,4-tri-O-benzyl-D-(6,6-(2)H(2))glucopyranoside was prepared and the deuterated O-6 primary alcohol was oxidized to an aldehyde by Swern oxidation. Stereoselective reduction with nondeuterated (R)-(+)-Alpine-Borane gave methyl 2,3,4-tri-O-benzyl-(6S)-D-(6-(2)H(1))glucopyranoside, which was deprotected under standard conditions to afford the title compound. The key stereoselective reduction step was achieved in 90% yield. The preparation uses economical, commercially available starting materials and will be useful for elucidating biosynthetic mechanisms.     

Synthesis of oligosaccharides containing the X-antigenic trisaccharide (alpha-L-Fucp-(1----3)-[beta-D-Galp-(1----4)]-beta-D-GlcpNAc) at their nonreducing ends.

The "armed" methyl 2,3,4-tri-O-benzyl-1-thio-beta-L-fucopyranoside was reacted with "disarmed" phenyl O-(tetra-O-acetyl-beta-D-galactopyranosyl)-(1----4)-6-O-benzyl-2- deoxy-2-phthalimido-1-thio-beta-D-glucopyranoside in the presence of CuBr2-Bu4NBr complex to give phenyl O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-(1----4)-O- [(2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl)-(1----3])-6-O-benzyl-2-deoxy -2- phthalimido-1-thio-beta-D-glucopyranoside (6) as a novel glycosyl donor. The glycosylating capability of 6 was further examined using N-iodosuccinimide-triflic acid as a reagent. This led to the synthesis of a tetrasaccharide and a pentasaccharide incorporating the X-antigenic structure represented by 6.     

Oxidative dimer produced from a 2,3,4-trihydroxybenzoic ester

The DPPH radical-scavenging abilities of the naturally occurring phenolic acid, 2,3,4-trihydroxybenzoic acid, and its methyl ester were evaluated. Both compounds in acetonitrile scavenged as many as four radicals compared to three or fewer radical consumption in acetone or ethanol. Only the ester showed relatively high ability in methanol. Oxidation with o-chloranil in acetonitrile resulted in methyl 2,3,4-trihydroxybenzoate giving a novel benzocoumarin-type dimer, its chemical structure being confirmed by spectroscopic evidence. The formation of this dimer might partly account for the higher radical-scavenging efficiency of the ester in acetonitrile or methanol.