A practical synthesis of alpha-D-Manp-(1-->3)-alpha-D-Manp-(1-->2)-[alpha-D-Glcp-(1-->3)]-alpha-D-Manp-(1-->2)-alpha-D-Manp-(1-->2)-alpha-D-Manp, an O-specific heterohexasaccharide fragment of Citrobacter braakii O7a, 3b, 1c

An O-specific heterohexasaccharide fragment of Citrobacter braakii O7a, 3b, 1c, alpha-D-Manp-(1-->3)-alpha-D-Manp-(1-->2)-[alpha-D-Glcp-(1-->3)]-alpha-D-Manp-(1-->2)-alpha-D-Manp-(1-->2)-alpha-D-Manp was synthesized as its methyl glycoside. Acetylation of allyl 4,6-O-benzylidene-alpha-D-mannopyranoside, followed by debenzylidenization and benzoylation gave allyl 2,3-di-O-acetyl-4,6-di-O-benzoyl-alpha-D-mannopyranoside (3), and subsequent deacetylation of 3 with CH(3)COCl-MeOH gave the monosaccharide acceptor 4. Condensation of isopropyl 2,3,4,6-tetra-O-benzyl-1-thio-beta-D-glucopyranoside (6) with 4 selectively afforded the alpha-(1-->3)-linked disaccharide 7. Condensation of 7 with the (1-->3)-linked disaccharide donor 9, followed by deallylation and trichloroacetimidation, afforded the tetrasaccharide donor 12. Coupling of 12 with disaccharide acceptor 13, followed by debenzylation and deacylation, furnished the target heterohexasaccharide 16.     

An efficient and concise synthesis of a beta-(1-->6)-linked D-galactofuranosyl hexasaccharide

A beta-(1-->6)-linked D-galactofuranosyl hexasaccharide was synthesized efficiently in a block construction manner by the well-known Schmidt glycosylation method using 6-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-galactofuranosyl trichloroacetimidate (1) and allyl 2,3,5-tri-O-benzoyl-beta-D-galactofuranoside (3) as the key synthons. Coupling of 3 with 1 gave beta-(1-->6)-linked disaccharide 4. Subsequent selective deacetylation of 4 afforded the disaccharide acceptor 5, while deallylation of 4 followed by trichloroacetimidate formation produced the disaccharide donor 6. Condensation of 5 with 6 gave the tetrasaccharide 7, and subsequent deacetylation afforded the tetrasaccharide acceptor 8. Finally, coupling of 8 with 6 followed by deacylation yielded the target beta-(1-->6)-linked galactofuranose hexasaccharide 10. All of the reactions in the synthesis were carried out smoothly and in high yield.     

Synthesis of a hexasaccharide fragment of the O-deacetylated GXM of C. neoformans serotype B

beta-D-Xylp-(1-->4)-alpha-D-Manp-(1-->3)-[beta-D-Xylp-(1-->2)]-alpha-D-Manp-(1-->3)-[beta-D-Xylp-(1-->2)]-alpha-D-Manp, the fragment of the exopolysaccharide from Cryptococcus neoformans serovar B, was synthesized as its methyl glycoside. Thus, acetylation of allyl 3-O-benzoyl-4,6-O-benzylidene-alpha-D-mannopyranoside (1) followed by debenzylidenation and selective 6-O-benzoylation afforded allyl 2-O-acetyl-3,6-di-O-benzoyl-alpha-D-mannopyranoside (4). Glycosylation of 4 with 2,3,4-tri-O-benzoyl-D-xylopyranosyl trichloroacetimidate (5) furnished the beta-(1-->4)-linked disaccharide 6. Deallylation followed by trichloroacetimidate formation gave the disaccharide donor 8, and subsequent coupling with allyl 2,3,4-tri-O-benzoyl-beta-D-xylopyranosyl-(1-->2)-4,6-di-O-benzoyl-alpha-D-mannopyranoside (9), produced the tetrasaccharide 10. Reiteration of deallylation and trichloroacetimidate formation from 10 yielded the tetrasaccharide donor 12. The downstream disaccharide acceptor 18 was obtained by condensation of 5 with methyl 3-O-acetyl-4,6-O-benzylidene-alpha-D-mannopyranoside, followed by debenzylidenation, benzoylation, and selective 3-O-deacetylation. Coupling of 18 with 12 afforded the hexasaccharide 19, and subsequent deprotection gave the hexasaccharide glycoside 20. Selective 2"-O-deacetylation of 19 gave the hexasaccharide acceptor 21. Condensation of 21 with glucopyranosyluronate imidate 22 did not produce the expected heptasaccharide glycoside; instead, a transacetylation product 19 was obtained. Meanwhile, there was no reaction between 21 and the bromide donor 23.     

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.     

A facile and effective synthesis of alpha-(1-->6)-linked mannose di-, tri-, tetra-, hexa-, octa-, and dodecasaccharides, and beta-(1-->6)-linked glucose di-, tri-, tetra-, hexa-, and octasaccharides using sugar trichloroacetimidates as the donors and unprotected or partially protected glycosides as the acceptors

Reaction of 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl trichloroimidate with allyl alpha-D-mannopyranoside in the presence of TMSOTf selectively gave allyl 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl-(1-->6)-alpha-D-mannopyranoside through an orthoester intermediate. Benzoylation of 3, followed by deallylation, and then trichloroimidation afforded the disaccharide donor 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl-(1-->6)-2,3,4-tri-O-benzoyl-alpha-D-mannopyranosyl trichloroimidate, while benzoylation of 3 followed by selective removal of acetyl groups yielded the disaccharide acceptor allyl alpha-D-mannopyranosyl-(1-->6)-2,3,4-tri-O-benzoyl-alpha-D-mannopyranoside. Coupling of 5 with 6 gave the tetrasaccharide allyl 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl-(1-->6)-2,3,4-tri-O-benzoyl-alpha-D-mannopyranosyl-(1-->6)-alpha-D-mannopyranosyl-(1-->6)-2,3,4-tri-O-benzoyl-alpha-D-mannopyranoside, which were converted into the tetrasaccharide donor 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl-(1-->6)-2,3,4-tri-O-benzoyl-alpha-D-mannopyranosyl-(1-->6)-2,3,4-tri-O-benzoyl-alpha-D-mannopyranosyl-(1-->6)-2,3,4-tri-O-benzoyl-alpha-D-mannopyranosyl trichloroimdate and the tetrasaccharide acceptor allyl alpha-D-mannopyranosyl-(1-->6)-2,3,4-tri-O-benzoyl-alpha-D-mannopyranosyl-(1-->6)-2,3,4-tri-O-benzoyl-alpha-D-mannopyranosyl-(1-->6)-2,3,4-tri-O-benzoyl-alpha-D-mannopyranoside, respectively, by the same strategies as used for conversion of 3 into 5 and 6. Condensation of 5 with 13 gave the hexasaccharide 14, while condensation of 12 with 13 gave the octasaccharide 17. Dodecasaccharide 21 was obtained by the coupling of 12 with the octasaccharide acceptor 20. Similar strategies were used for the syntheses of beta-(1-->6)-linked glucose di-, tri-, tetra-, hexa-, and octamers. Deprotection of the oligosaccharides in ammonia-saturated methanol yielded the free alpha-(1-->6)-linked mannosyl and beta-(1-->6)-linked glucosyl oligomers.     

Synthesis of a heptasaccharide fragment of the O-deacetylated GXM of C. neoformans serotype C

Beta-D-Xylp-(1-->2)-alpha-D-Manp-(1-->3)-[beta-D-Xylp-(1-->2)][beta-D-Xylp-(1-->4)]-alpha-D-Manp-(1-->3)-[beta-D-Xylp-(1-->4)]-alpha-D-Manp, the fragment of the exopolysaccharide from Cryptococcus neoformans serovar C, was synthesized as its methyl glycoside. Thus, chloroacetylation of allyl 3-O-acetyl-4,6-O-benzylidene-alpha-D-mannopyranoside (1) followed by debenzylidenation and selective 6-O-benzoylation afforded allyl 2-O-chloroacetyl-3-O-acetyl-6-O-benzoyl-alpha-D-mannopyranoside (4). Glycosylation of 4 with 2,3,4-tri-O-benzoyl-D-xylopyranosyl trichloroacetimidate (5) furnished the beta-(1-->4)-linked disaccharide 6. Dechloroacetylation gave the disaccharide acceptor 7 and subsequent coupling with 5 produced the trisaccharide 8. Deacetylation of 8 gave the trisaccharide acceptor 9 and subsequent coupling with a disaccharide 10 produced the pentasaccharide 11. Reiteration of deallylation and trichloroacetimidate formation from 11 yielded the pentasaccharide donor 12. Coupling of a disaccharide acceptor 13 with 12 afforded the heptasaccharide 14. Subsequent deprotection gave the heptaoside 16, while selective 2-O-deacetylation of 14 gave the heptasaccharide acceptor 15. Condensation of 15 with glucopyranosyluronate imidate 17 did not yield the expected octaoside, instead, an orthoester product 18 was obtained. Rearrangement of 18 did not give the target octaoside; but produced 15. Meanwhile, there was no reaction between 15 and the glycosyl bromide donor 19.     

Synthesis of alpha-Manp-(1-->2)-alpha-Manp-(1-->3)-alpha-Manp-(1-->3)-Manp, the tetrasaccharide repeating unit of Escherichia coli O9a, and alpha-Manp-(1-->2)-alpha-Manp-(1-->2)-alpha-Manp-(1-->3)-alpha-Manp-(1-->3)-Manp, the pentasaccharide repeating unit of E. coli O9 and Klebsiella O3

The tetrasaccharide repeating unit of Escherichia coli O9a, alpha-D-Manp-(1-->2)-alpha-D-Manp-(1-->3)-alpha-D-Manp-(1-->3)-D-Manp, and the pentasaccharide repeating unit of E. coli O9 and Klebsiella O3, alpha-D-Manp-(1-->2)-alpha-D-Manp-(1-->2)-alpha-D-Manp-(1-->3)-alpha-D-Manp-(1-->3)-D-Manp, were synthesized as their methyl glycosides. Thus, selective 3-O-allylation of p-methoxyphenyl alpha-D-mannopyranoside via a dibutyltin intermediate gave p-methoxyphenyl 3-O-allyl-alpha-D-mannopyranoside (2) in good yield. Benzoylation (-->3), then removal of 1-O-methoxyphenyl (right arrow4), and subsequent trichloroacetimidation afforded the 3-O-allyl-2,4,6-tri-O-benzoyl-alpha-D-mannopyranosyl trichloroacetimidate (5). Condensation of 5 with methyl 4,6-O-benzylidene-alpha-D-mannopyranoside (6) selectively afforded the (1-->3)-linked disaccharide 7. Benzoylation of 7, debenzylidenation, benzoylation, and deallylation gave methyl 2,4,6-tri-O-benzoyl-alpha-D-mannopyranosyl-(1-->3)-2,4,6-tri-O-benzoyl-alpha-D-mannopyranoside (11) as the disaccharide acceptor. Coupling of 11 with (1-->2)-linked mannose disaccharide donor 17 or trisaccharide donor 21, followed by deacylation, furnished the target tetrasaccharide and pentasaccharide, respectively.     

Synthesis of an alpha-linked dimer of the trisaccharide repeating unit of the exopolysaccharide produced by Pediococcus damnosus 2.6

A hexasaccharide, beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->2)]-alpha-D-Glcp-(1-->3)-beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->2)]-D-Glcp, the alpha-linked dimer of the trisaccharide repeating unit of the exopolysaccharide produced by Pediococcus damnosus 2.6, was synthesized as its methyl glycoside. Condensation of fully benzoylated alpha-D-glucopyranosyl trichloroacetimidate (1) with isopropyl 4,6-O-benzylidene-1-thio-beta-D-glucopyranoside (2) selectively furnished (1-->3)-linked disaccharide 3, and subsequent 2-O-acetylation, desulfation, and trichloroacetimidate formation afforded the disaccharide donor 6. Meanwhile, selective 3-O-coupling of methyl 4,6-O-benzylidene-alpha-d-glucopyranoside (8) with 3-O-allyl-2,4,6-tri-O-benzoyl-alpha-D-glucopyranosyl trichloroacetimidate (7), followed by coupling with 1 gave the trisaccharide 10. Removal of the benzylidene group of 10, benzoylation, and deallylation produced the trisaccharide acceptor 12. Condensation of 12 with 6 yielded a pentasaccharide mixture 13 with beta and alpha isomers in a ratio of 2:1. Removal of the benzylidene group of 13, followed by benzoylation gave the pentasaccharide mixture 14. Selective 2'-deacetylation of the isolated beta-linked 14beta with MeCOCl/MeOH/CH2Cl2 did not give the expected pentasaccharide acceptor, and serious decomposition occurred, indicating a large steric hindrance at C-2'. Alternatively, 2,3-di-O-glycosylation of allyl 4,6-O-benzylidene-beta-D-glucopyranoside (21) with 1 gave 22, then deallylation and trichloroacetimidate formation afforded the trisaccharide donor 24. Condensation of 12 with 24 furnished only the alpha-linked hexasaccharide 25, and its deprotection gave the free hexaoside 27.     

Concise syntheses of arabinogalactans with beta-(1-->6)-linked galactopyranose backbones and alpha-(1-->3)- and alpha-(1-->2)-linked arabinofuranose side chains

4-methoxyphenyl glycosides of 2,3'-bis-alpha-L-arabinofuranosyl branched beta-D-(1-->6)-linked galactopyranosyl tetraose (16), 3',2'-bis-alpha-L-arabinofuranosyl branched beta-D-(1-->6)-linked galactopyranosyl hexaose (27), and a twentyose (42) consisting of beta-(1-->6)-linked D-galactopyranosyl pentadecaoligosaccharide backbone with alpha-L-arabinofuranosyl side chains alternately attached at C-2 and C-3 of the middle galactose residue of each consecutive beta-(1-->6)-linked galactotriose unit of the backbone, were synthesized with isopropyl 3-O-allyl-2,4-di-O-benzoyl-1-thio-beta-D-galactopyranoside (6), 2,3,4,6-tetra-O-benzoyl-alpha-D-galactopyranosyl trichloroacetimidate (7), 2,3,5-tri-O-benzoyl-alpha-L-arabinofuranosyl trichloroacetimidate (12), 6-O-acetyl-2,3,4-tri-O-benzoyl-alpha-D-galactopyranosyl trichloroacetimidate (17), 4-methoxyphenyl 2,3,4-tri-O-benzoyl-beta-D-galactopyranoside (19), and 2,6-di-O-acetyl-3,4-di-O-benzoyl-alpha-D-galactopyranosyl trichloroacetimidate (28) as the key synthons. Condensation of 6 with 7 gave the disaccharide donor 8, and subsequent condensation of 8 with 4-methoxyphenyl 2,3,4-tri-O-benzoyl-beta-D-galactopyranosyl-(1-->6)-2-O-acetyl-3,4-di-O-benzoyl-beta-D-galactopyranoside (9) followed by selective deacetylation afforded the tetrasaccharide acceptor 11. Coupling of 11 with 12 gave the pentasaccharide 13, its deallylation followed by coupling with 12, and debenzoylation gave the hexasaccharide 16 with beta-(1-->6)-linked galactopyranose backbone and 2- and 3'-linked alpha-L-arabinofuranose side chains. The octasaccharide 27 was similarly synthesized, while the twentyoside 42 was synthesized with tetrasaccharides 33 or 24 as the donors and 23, 36, 38, and 40 as the acceptors by consecutive couplings followed by deacylation.     

Syntheses of beta-(1-->6)-branched beta-(1-->3)-linked d-galactans that exist in the rhizomes of Atractylodes lancea DC

Effective syntheses of galactose hepta-, octa-, nona-, and decasaccharides that exist in the rhizomes of Atractylodes lancea DC were achieved with 2,3,4,6-tetra-O-benzoyl-alpha-d-galactopyranosyl trichloroacetimidate (1), 4-methoxyphenyl 2,3,4-tri-O-benzoyl-beta-d-galactopyranoside (2), 6-O-acetyl-2,3,4-tri-O-benzoyl-alpha-d-galactopyranosyl trichloroacetimidate (5), 4-methoxyphenyl 6-O-acetyl-2,4-di-O-benzoyl-beta-d-galactopyranoside (22), and 4-methoxyphenyl 2,4,6-tri-O-benzoyl-beta-d-galactopyranoside (26) as the key synthons. Coupling of 2 with 1, followed by oxidative cleavage of 1-OMP and subsequent trichloroacetimidate formation gave the beta-(1-->6)-linked disaccharide donor 4. Condensation of 2 with 5 and subsequent selective deacetylation by methanolysis produced the beta-(1-->6)-linked disaccharide acceptor 7. Reaction of 7 with 4, oxidative cleavage of 1-OMP, and trichloroacetimidate formation produced the tetrasaccharide donor 9. The penta- (15), the hexa- (17), and the heptasaccharide donor 19 were synthesized similarly. Meanwhile, treatment of 1 with 22 yielded beta-(1-->3)-linked disaccharide 23 and alpha-(1-->3)-linked disaccharide 25. Oxidative cleavage of 1-OMp of 23 followed by trichloroacetimidate formation produced the disaccharide donor 24. Coupling of 26 with 24, again, gave beta-linked 27 and alpha-linked 29. Selective 6-O-deacetylation of 27 afforded the trisaccharide acceptor 28. TMSOTf-promoted condensation 28 of with the tetra- (9), penta- (15), hexa-(17), and heptasaccharide donor 19, followed by deprotection, gave the target compounds.     

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.     

Synthesis of beta-D-glucose oligosaccharides from Phytophthora parasitica

The glucohexaose, beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->6)]-beta-D-Glcp-(1-->3)-D-Glcp, was synthesized as its allyl glycoside via 3+3 strategy. The trisaccharide donor, 2,3,4,6-tetra-O-benzoyl-beta-D-glucopyranosyl-(1-->3)-2,4,6-tri-O-acetyl-beta-D-glucopyranosyl-(1-->3)-2,4,6-tri-O-acetyl-alpha-D-glucopyranosyl trichloroacetimidate (11), was obtained by 3-selective coupling of isopropyl 4,6-O-benzylidene-1-thio-beta-D-glucopyranoside (2) with 2,3,4,6-tetra-O-benzoyl-beta-D-glucopyranosyl-(1-->3)-2-O-acetyl-4,6-O-benzylidene-alpha-D-glucopyranosyl trichloroacetimidate (6), followed by hydrolysis, acetylation, dethiolation, and trichloroacetimidation. Meanwhile, the trisaccharide acceptor, allyl 2,3,4,6-tetra-O-benzoyl-beta-D-glucopyranosyl-(1-->3)-2-O-acetyl-beta-D-glucopyranosyl-(1-->3)-4,6-di-O-acetyl-2-O-benzoyl-alpha-D-glucopyranoside (14), was prepared by coupling of allyl 4,6-di-O-acetyl-2-O-benzoyl-alpha-D-glucopyranoside (12) with 6, followed by debenzylidenation. Condensation of 14 with 11, followed by deacylation, gave the target hexaoside. A beta-(1-->3)-linked tetrasaccharide 29 was also synthesized with methyl 2-O-benzoyl-4,6-O-benzylidene-beta-D-glucopyranosyl-(1-->3)-2,4,6-tri-O-acetyl-beta-D-glucopyranoside (25) as the acceptor and acylated beta-(1-->3)-linked disaccharide 21 as the donor.     

A concise synthesis of two isomeric pentasaccharides, the O repeat units from the lipopolysaccharides of P. syringae pv. porri NCPPB 3364T and NCPPB 3365

A concise synthesis of two isomeric pentasaccharides, alpha-L-Rhap-(1-->2)-alpha-L-Rhap-(1-->3)-alpha-L-Rhap-(1-->3)-[beta-D-GlcpNAc-(1-->2)]-alpha-L-Rhap (A) and alpha-L-Rhap-(1-->2)-alpha-L-Rhap-(1-->3)-[beta-D-GlcpNAc-(1-->2)]-alpha-L-Rhap-(1-->3)-alpha-L-Rhap (B), the O repeats from the lipopolysaccharides of Pseudonomonas syringae pv. porri NCPPB 3364T and 3365 was achieved via assembly of the building blocks, allyl 3,4-di-O-benzoyl-alpha-L-rhamnopyranoside (1), 2,3,4-tri-O-benzoyl-alpha-L-rhamnopyranosyl trichloroacetimidate (2), allyl 4-O-benzoyl-3-O-chloroacetyl-alpha-L-rhamnopyranoside (6), 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-beta-D-glucopyranosyl trichloroacetimidate (7), and allyl 2,4-di-O-benzoyl-alpha-L-rhamnopyranoside (10). Coupling of 1 with 2 followed by deallylation and trichloroacetimidate formation gave the disaccharide donor 5, while condensation of 6 with 7, followed by dechloroacetylation, offered the disaccharide acceptor 9. Then, 5 was coupled with 10 to obtain the trisaccharide 11, and subsequent deallylation and trichloroacetimidate formation furnished the trisaccharide donor 13. Coupling of 9 with 13, followed by deprotection, afforded pentasaccharide 19, while condensation of 9 with 5, followed by deallylation and trichloroacetimidate formation, gave the tetrasaccharide donor 16, whose coupling with 10 and subsequent deprotection yielded another pentasaccharide 22.     

Synthesis of a mannose heptasaccharide of the pathogenic yeast,Candida glabrata IFO 0622 strain

An effective synthesis of the mannose heptasaccharide existing in the pathogenic yeast, Candida glabrata IFO 0622 strain was achieved via TMSOTf-promoted condensation of a tetrasaccharide donor 13 with a trisaccharide acceptor 16, followed by deprotection. The tetrasaccharide 13 was constructed by coupling of 2,3,4,6-tetra-O-benzoyl-alpha-D-mannopyranosyl-(1-->3)-2,4,6-tri-O-acetyl-alpha-D-mannopyranosyl trichloroacetimidate (7) with allyl 3,4,6-tri-O-benzoyl-alpha-D-mannopyranosyl-(1-->2)-3,4,6-tri-O-benzoyl-alpha-D-mannopyranoside (10), followed by deallylation and trichloroacetimadation. The trisaccharide 16 was obtained by coupling of 6-O-acetyl-2,3,4-tri-O-benzoyl-alpha-D-mannopyranosyl trichloroacetimidate with 10, and subsequent 6-O-deacetylation. The disaccharide 7 was prepared through coupling of perbenzoylated mannosyl trichloroacetimidate with 4,6-O-benzylidene-1,2-O-ethylidene-beta-D-mannopyranose, then simultaneous debenzylidenation and deethylidenation, and subsequent acetylation, selective 1-O-deacetylation, and trichloroacetimidation. The disaccharide 10 was obtained by self-condensation of 3,4,6-tri-O-benzoyl-1,2-O-allyloxyethylidene-beta-D-mannopyranose, followed by selective 2-O-deacetylation.     

Synthesis of alpha-series ganglioside GM1alpha containing C20-sphingosine

A synthesis of alpha-series ganglioside GM1alpha (III(6)Neu5AcGgOse4Cer) containing C20-sphingosine(d20:1) is described. Glycosylation of 2-(trimethylsilyl)ethyl 2,3,6-tri-O-benzyl-beta-D-galactopyranosyl-(1-->4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside with the glucosamine donor ethyl 3-O-acetyl-2-deoxy-4,6-O-[(4-methoxyphenyl)methylene]-2-phthalimido-1-thio-beta-D-glucopyranoside furnished a beta-(1-->4)-linked trisaccharide. Reductive cleavage of the p-methoxybenzylidene group followed by intramolecular inversion of its triflate afforded the desired trisaccharide, which was transformed into a trisaccharide acceptor via removal of the phthaloyl and O-acetyl groups followed by N-acetylation. A tetrasaccharide acceptor was obtained by glycosylation of the trisaccharide acceptor with dodecyl 2,3,4,6-tetra-O-benzoyl-1-thio-beta-D-galactopyranoside, followed by removal of the p-methoxybenzyl group. Coupling of the tetrasaccharide acceptor with ethyl (methyl 4,7,8,9-tetra-O-acetyl-3,5-dideoxy-1-thio-5-trichloroacetamido-D-glycero-D-galacto-2-nonulopyranosid)onate and subsequent radical reduction gave the desired GM1alpha saccharide derivative, which was coupled with (2S,3R,4E)-2-azido-3-O-benzoyl-4-eicosene-1,3-diol after conversion into the imidate.     

Synthesis of an xylosylated rhamnose pentasaccharide, the repeating unit of the O-chain polysaccharide of the lipopolysaccharide of Xanthomonas campestris pv. begoniae GSPB 525

A xylosylated rhamnose pentasaccharide, alpha-L-Rhap-(1-->3)-[beta-L-Xylp-(1-->2)-]-alpha-L-Rhap-(1-->3)-[beta-L-Xylp-(1-->4)]-L-Rhap, the repeating unit of the O-chain polysaccharide (OPS) of the lipopolysaccharides of Xanthomonas campestris pv. begoniae GSPB 525 was synthesized by a highly regio- and stereoselective way. Thus coupling of 1,2-O-ethylidene-beta-L-rhamnopyranose (1) with 2,3,4-tri-O-benzoyl-alpha-L-rhamnopyranosyl trichloroacetimidate (2) to give (1-->3)-linked disaccharide (3), subsequent benzoylation, deethylidenation, acetylation, 1-O-deacetylation, and trichloroacetimidation afforded the disaccharide donor 11. Condensation of 11 with 1 yielded 2,3,4-tri-O-benzoyl-alpha-L-rhamnopyranosyl-(1-->3)-2-O-acetyl-4-O-benzoyl-alpha-L-rhamnopyranosyl-(1-->3)-1,2-O-ethylidene-beta-L-rhamnopyranose (12), and selective deacetylation of 12 yielded the trisaccharide diol acceptor 15. Coupling of 15 with 2,3,4-tri-O-benzoyl-alpha-L-xylopyranosyl trichloroacetimidate (16), followed by deprotection, gave the target pentasaccharide 19.     

A highly efficient synthesis of an octasaccharide,the repeating unit of the cell-wall mannan of Trichophyton mentagrophytes and T. rubrum

A highly concise and effective synthesis of the mannose octasaccharide repeating unit of the cell-wall mannan of Trichophyton mentagrophytes and T. rubrum was achieved via 6-O-glycosylation of a tetrasaccharide acceptor with a tetrasaccharide donor, followed by deprotection. The key tetrasaccharide (11) was constructed by selective 6-O-glycosylation of allyl 3,4-di-O-benzoyl-alpha-D-mannopyranosyl-(1-->6)-2,3,4-tri-O-benzoyl-alpha-D-mannopyranoside with 6-O-acetyl-2,3,4-tri-O-benzoyl-alpha-D-mannopyranosyl trichloroacetimidate, then with 2,3,4,6-tetra-O-benzoyl-alpha-D-mannopyranosyl trichloroacetimidate. The tetrasaccharide acceptor (13) was obtained by selective 6-O-deacetylation of 11, while the tetrasaccharide donor 12 was obtained by deallylation of 11, followed by trichloroacetimidation.     

An effective synthesis of an arabinogalactan with a beta-(1-->6)-linked galactopyranose backbone and alpha-(1-->2) arabinofuranose side chains

An octasaccharide, beta-D-Galp-(1-->6)-[alpha-L-Araf-(1-->2)]-beta-D-Galp-(1-->6)-beta-D-Galp-(1-->6)-[alpha-L-Araf-(1-->5)-alpha-L-Araf-(1-->2)]-beta-D-Galp-(1-->6)-beta-D-Galp-1-->OMP was synthesized. 4-methoxyphenyl 2,3,4-tri-O-benzoyl-beta-D-galactopyranoside (5), 2,6-di-O-acetyl-3,4-di-O-benzoyl-alpha-D-galactopyranosyl trichloroacetimidate (9), and 4-methoxyphenyl 2-O-acetyl-3,4-di-O-benzoyl-beta-D-galactopyranoside (11), 2,3,4,6-tetra-O-benzoyl-alpha-D-galactopyranosyl trichloroacetimidate (12), and 2,3,5-tri-O-benzoyl-alpha-L-arabinofuranosyl trichloroacetimidate (17) were used as the synthons. A concise route was used to gain the tetrasaccharide donor 19 by the use of 11, 12, 5, and 17. Meanwhile, treatment of 5 with 9 yielded beta-(1-->6)-linked disaccharide 20, and subsequent selective 6-O-deacetylation produced the disaccharide acceptor 21. Reaction of 21 with 19 gave 22, and subsequent selective 2-O-deacetylation afforded the hexasaccharide acceptor 23. Condensation of 23 with alpha-L-(1-->5)-linked arabinofuranose disaccharide 24, followed by deprotection, yielded the target octasaccharide.     

Synthesis of (R)-2,3-epoxypropyl(1-->3)-beta-D-pentaglucoside

The title pentasaccharide was synthesized via a 2+3 strategy. The disaccharide donor, 3-O-acetyl-2-O-benzoyl-4,6-O-benzylidene-beta-D-glucopyranosyl-(1-->3)-2-O-benzoyl-4,6-O-benzylidene-alpha-D-glucopyranosyl trichloroacetimidate (8), was obtained by selective coupling of allyl 2-O-benzoyl-4,6-O-benzylidene-alpha-D-glucopyranoside with 3-O-acetyl-2-O-benzoyl-4,6-O-benzylidene-alpha-D-glucopyranosyl trichloroacetimidate (4), followed by deallylation, and trichloroacetimidation. Meanwhile, the trisaccharide acceptor, allyl 2-O-benzoyl-4,6-O-benzylidene-beta-D-glucopyranosyl-(1-->3)-2-O-benzoyl-4,6-O-benzylidene-beta-D-glucopyranosyl-(1-->3)-2-O-benzoyl-4,6-O-benzylidene-beta-D-glucopyranoside (12), was prepared by coupling of allyl 2-O-benzoyl-4,6-O-benzylidene-beta-D-glucopyranosyl-(1-->3)-2-O-benzoyl-4,6-O-benzylidene-beta-D-glucopyranoside with 4, followed by deacetylation. Condensation of 8 with 12, followed by epoxidation, and deprotection, gave the target pentaoside.     

Synthesis of a mannose heptasaccharide existing in baker's yeast,Saccharomyces cerevisiae X2180-1A wild-type strain

A mannose heptasaccharide existing in baker's yeast, Saccharomyces cerevisiae X2180-1A wild-type strain, was effectively synthesized as its allyl glycoside via TMSOTf-promoted condensation of a disaccharide donor 13 with a pentasaccharide acceptor 12, followed by deprotection. The pentasaccharide 12 was constructed by coupling of 2,3,4,6-tetra-O-benzoyl-alpha-D-mannopyranosyl-(1-->3)-2,4,6-tri-O-benzoyl-alpha-D-mannopyranosyl-(1-->2)-3,4,6-tri-O-benzoyl-alpha-D-mannopyranosyl-(1-->2)-3,4,6-tri-O-benzoyl-alpha-D-mannopyranosyl trichloroacetimidate (9) with allyl 6-O-acetyl-3,4-di-O-benzoyl-alpha-D-mannopyranoside (10), followed by deacetylation. The tetrasaccharide 9 was obtained by coupling of 2,3,4,6-tetra-O-benzoyl-alpha-D-mannopyranosyl-(1-->3)-2,4,6-tri-O-benzoyl-alpha-D-mannopyranosyl trichloroacetimidate (5) with allyl 3,4,6-tri-O-benzoyl-alpha-D-mannopyranosyl-(1-->2)-3,4,6-tri-O-benzoyl-alpha-D-mannopyranoside (6), followed by deallylation and trichloroacetimidation. The disaccharides 6 and 13 were readily obtained by known methods.