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1.
N-Acetylneuraminic acid ( 1 ) can be transformed into the methyl α-D -ketoside 2 which, by reaction with methanesulfonyl chloride, yields the corresponding 4-O-mesylate 3 and the 4,7-di-O-mesylate 4 as a by-product. Compound 3 reacts with Nal giving the 4-deoxy-4-iodo compound 5 with equatorial orientation of the I-atom. As second product, the dihydrooxazole 6 is produced. Catalytic hydrogenation of 5 is followed by ester cleavage and removal of the isopropylidene group yielding the methyl α-D -ketoside 8 which affords the title compound, N-acetyl-4-deoxyneuraminic acid ( 9 ), by reaction with fowl plague virus sialidase. Further biochemical activities of 8 and 9 are reported. 相似文献
2.
The synthesis of 5-acetamido-4-deoxyneuraminic acid ( 1 ) is described. Acetylation of a mixture of the epimeric triols 4 and 5 gave the tetraacetates 7 and 8 (Scheme 1). Ozonolysis of a mixture of these acetates followed by base-promoted β-elimination led to the (E) -configurated α,β-unsaturated keto ester 10 , which was hydrogenated to give the saturated keto ester 11 . Saponification of 11 and hydrolytic removal of the benzylidene group followed by anion-exchange chromatography gave the 5-acetamido-4-deoxyneuraminic acid ( 1 , Scheme 1 and 2). De-O-acetylation (NaOMe/MeOH) of the keto ester 11 gave a mixture of the tert-butyl ester 12 and the methyl ester 13 , which were converted to tert-butyl N-acetyl-4-deoxyneuraminate ( 14 ) and to methyl N-acetyl-4-deoxyneuraminate ( 15 ), respectively. Hydrogenolysis of the benzylidene acetal 11 followed by de-O-acetylation gave the pentahydroxy ester 16 . 相似文献
3.
Akira Hasegawa Takashi Ando Akihiko Kameyama Makoto Kiso 《Journal of carbohydrate chemistry》2013,32(5):645-658
Abstract Stereocontrolled synthesis of sialyl Lex epitope and its ceramide derivative with regard to the introduction of galactose or β-D-galactosyl ceramide into the terminal N-acetylglucosamine residue of sialyl Lex determinant is described. Königs-Knorr condensation of 2-(trimethylsilyl)ethyl 2, 4, 6-tri-O-benzyl-β-D-galactopyranoside (4) with 3, 4, 6-tri-O-acetyl-2-deoxy-2-phthalimido-D-glucopyranosyl bromide (5) gave the desired β-glycoside 6, which was converted into 2-(trimethylsilyl)ethyl O-(2-acetamido-4, 6-O-benzylidene-2-deoxy-β-D-glucopyranosyl)-(l→3)-2, 4, 6-tri-O-benzyl-β-D-galactopyranoside (8) via removal of the phthaloyl and O-acetyl groups, followed by N-acetylation and 4, 6-O-benzylidenation. Glycosylation of 8 with methyl 2, 3, 4-tri-O-benzyl-1-thio-β-L-fucopyranoside (9) gave the α-glycoside (10), which was transformed by reductive ring-opening of the benzyliderie acetal into the acceptor (11). Dimethyl(methylthio)sulfonium triflate (DMTST)-promoted coupling of 11 with methyl O-(methyl 5-acetamido-4, 7, 8, 9-tetra-O-acetyl-3, 5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→3)-2, 4, 6-tri-O-benzoyl-l-thio-β-D-galactopyra-noside (12) afforded the desired pentasaccharide (13), which was converted into the α-trichloroacetimidate 16 via reductive removal of the benzyl groups, then O-acetylation, removal of the 2-(trimethyIsilyl)ethyl group and treatment with trichloroacetonitrile. Condensation of 16 with (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-l, 3-diol (18) gave the β-glycoside 19, which was transformed into the title compound 21, via reduction of the azido group, coupling with octadecanoic acid, O-deacylation and hydrolysis of the methyl ester group. On the other hand, O-deacylation of 13 and subsequent hydrolysis of the methyl ester group gave the pentasaccharide epitope 17. 相似文献
4.
Akihiko Kameyama Hideharu Ishida Makoto Kiso Akira Hasegawa 《Journal of carbohydrate chemistry》2013,32(4):549-560
ABSTRACT The first total synthesis of tumor-associated glycolipid antigen, sialyl Lewis X is described. Glycosylation of 2-(trimethylsilyl)ethyl O-(2-acetamido-4,6-O-benzylidene-2-deoxy-β-D-glucopyranosyl)-(1→3)-O-(2,4,6-tri-O-benzyl-β-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-β-D-glucopyranoside (1) with methyl 2,3,4-tri-O-benzyl-1-thio-β-L-fuco-pyranoside (4) gave the α-glycoside (5), which was converted by reductive ring-opening of the benzylidene acetal into the glycosyl acceptor (6). Dimethyl(methylthio)sulfonium triflate-promoted coupling of 6 with methyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→3)-2,4,6-tri-O-benzoyl-1-thio-β-D-galactopyranoside (7) afforded the desired hexasaccharide 8 in good yield. Compound 8 was converted into the α-trichloroacetimidate 11, via reductive removal of the benzyl groups, O-acetylation, removal of the 2-(trimethylsilyl)ethyl group, and treatment with trichloroacetonitrile, which, on coupling with (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octa-decene-1,3-diol (12), gave the β-glycoside 13. Finally, 13 was transformed, via selective reduction of the azide group, condensation with octadecanoic acid, O-deacylation, and hydrolysis of the methyl ester group, into the title compound 16. 相似文献
5.
Akira Hasegawa Hideki Ishida Takao Nagahama Makoto Kiso 《Journal of carbohydrate chemistry》2013,32(6):703-718
Abstract A stereo controlled, facile total synthesis of gangliosides GM1 and GD1a, in connection with systematic synthesis of ganglio-series of ganglioside, is described. Glycosylation of 2-(trimethylsilyl) ethyl O-(2-acetamido-6-O-benzoyl-2-deoxy-(β-D-galactopyranosyl)-(l→4)-O-[(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacro-2–nonulopyranosylonate)-(2→3)]-O-2,6-di-O-benzyl-β-D-galacto-pyranosyl)-(l→40)-2,3,6-tri-O-benzyl-β-D-glucopyranoside (4), with methyl 2,4,6-tri-O-benzoyl-3-O-benzyl-l-thio-β-D-galactopyranoside (8) or methyl O-(methyl 5-acetamido -4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacro-2-nonulopyranosylonate)-(2→3)-2,4,6-tri-O-benzoyl-l-thio-β-D-galactopyranoside (9) by use of N-iodosuccinimide (NIS)-trifluoromethanesulfonic acid (TfOH) or dimethyl(methylthio)sulfonium triflate (DMTST) as a promoter, gave the corresponding [β-glycoside 10 and 18 in 66 and 62% yields, which were converted, via reductive removal of the benzyl groups, O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, and subsequent imidate formation, into the α-trichloroacetimidates 13 and 21. Glycosylation of (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-l,3-diol (14) with 13 or 21 by use of trimethylsilyl trifluoromethanesulfonate gave the corresponding β-glycoside 15 and 22, which on channeling through selective reduction of die azido group, coupling of the thus formed amino group with octadecanoic acid, O-deacylation, and saponification of the methyl ester group, gave the tital gangliosides GM1 and GD1a. 相似文献
6.
Kenji Hotta Tomoko Kawase Hideharu Ishida Makoto Kiso Akira Hasegawa 《Journal of carbohydrate chemistry》2013,32(7):961-975
Abstract A first total synthesis of a β-series ganglioside GQ1β (IV3Neu5Acα2, III6Neu5Acα2-Gg4Cer) is described. Regio- and stereoselective dimeric sialylation of the hydroxyl group at C-6 of the GalNAc residue in 2-(trimethylsilyl)ethyl O-(2-acetamido-2-deoxy-3-O-levulinyl-β-d-galactopyranosyl)-(1→4)-O-(2,3,6-tri-O-benzyl-β-d-galactopyranosyl)-(1→4)-O-2,3,6-tri-O-benzyl-β-d-glucopyranoside (3) with methyl [phenyl 5-acetamido-8-O-(5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-d-glycero-α-d-galacto-2-nonulopyranosylono-1′,9-lactone)-4,7-di-O-acetyl-3,5-dideoxy-2-thio-d-glycero-d-galacto-2-nonulopyranosid]onate (4) using N-iodosuccinimide (NIS)-trifluoromethanesulfonic acid (TfOH) as a promoter gave the desired pentasaccharide 5 containing α-glycosidically-linked dimeric sialic acids. This was transformed into the acceptor 6 by removal of the levulinyl group. Condensation of methyl O-[methyl 5-acetamido-8-O-(5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-d-glycero-α-d-galacto-2-nonulopyranosylono-1′,9-lactone)-4,7-di-O-acetyl-3,5-dideoxy-d-glycero-d-galacto-2-nonulopyranosylonate]-(2→3)-2,4,6-tri-O-benzoyl-1-thio-β-d-galactopyranoside (7) with 6, using dimethyl(methylthio)sulfonium triflate (DMTST) as a promoter, gave the desired octasaccharide derivative 8 in high yield. Compound 8 was converted into α-trichloroacetimidate 11, via reductive removal of the benzyl groups, O-acetylation, removal of the 2-(trimethylsilyl)ethyl group, and treatment with trichloroacetonitrile, which, on coupling with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (12), gave the β-glycoside 13. Finally, 13 was transformed, via selective reduction of the azido group, coupling with octadecanoic acid, O-deacylation, and hydrolysis of the methyl ester group, into the title ganglioside 15 in good yield. 相似文献
7.
Yukihiro Isogai Hideharu Ishida Makoto Kiso Akira Hasegawa 《Journal of carbohydrate chemistry》2013,32(9):1119-1137
ABSTRACT 3-O-Sulfo glucuronyl neolactohexanosyl ceramide derivatives (heptasaccharides) have been synthesized. Condensation of 2-(trimethylsilyl)ethyl 2,4,6-tri-O-benzyl-β-D-galactopyranoside (2) with 4-O-acetyl-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl trichloroacetimidate (1) gave the desired β-glycoside 3, which was converted into 2-(trimethylsilyl)ethyl O-(2-acetamido-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranosyl)-(1→3)-2,4,6-tri-O-benzyl-β-D-galactopyranoside (4) via removal of the O-acetyl and N-phthaloyl groups, followed by N-acetylation. Glycosylation of 4 with O-(methyl 4-O-acetyl-2-O-benzoyl-3-O-levulinoyl-β-D-glucopyranosyluronate)-(1→3)-2,4,6-tri-O-benzoyl-α-D-galactopyranosyl trichloroacetimidate (5) using trimethylsilyl trifluoromethanesulfonate gave the target tetrasaccharide 6, which was transformed via removal of the benzyl group, O-benzoylation, removal of the 2-(trimethylsilyl)ethyl group and imidate formation into the tetrasaccharide donor 9. Glycosylation of 2-(trimethylsilyl)ethyl O-(2-acetamido-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranosyl)-(1→3)-O-(2,4,6-tri-O-benzyl-β-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-β-D-glucopyranoside (10) with the imidate donor 9 using trimethylsilyl trifluoromethanesulfonate gave the desired heptasaccharide 11, which was transformed into the heptasaccharide imidate donor 14. Glycosylation of (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (15) with 14 gave β-glycoside 16, which was transformed into the four target compounds, via reduction of the azido group, coupling with octadecanoic acid or tetracosanoic acid, selective removal of the levulinoyl group, O-sulfation, hydrolysis of the methyl ester group and O-deacylation. 相似文献
8.
Keisuke Adachi Yutaka Yamada Hiroaki Wada Akihiko Kameyama Hideharu Ishida Makoto Kiso 《Journal of carbohydrate chemistry》2013,32(4-5):595-607
Abstract Five sialyl Lew is X ganglioside analogs containing 4-(2-tetradecylhexadecanoylamino)benzyl group in place of ceramide and a variety of lengths of ethylene glycol chains as the spacer, have been synthesized. Glycosidation of O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-glacto-2-nonulopyranosylonate)-(2→3)-O-(4-O-acetyl-2,6-di-O-benzoyl-β-D-galactopyranosyl)-(1→4)-O-[(2,3,4-tri-O-acetylα-L-fucopyranosyl)-(1→3)]-2,4-di-O-benzoyl-α-D-glucopyranosyl trichloroacetimidate (13) with oligo ethyleneglycol monobenzyl ether derivatives 9, 10, 11 and 12, prepared from the corresponding oligo ethyleneglycols by 4-nitrobenzylation, reduction and N-acylation with 2-tetradecylhexadecanoic acid, using boron trifluoride etherate gave the corresponding glycolipid derivatives 14, 15, 16 and 17. A similar glycosidation of 13 with 4-nitrobenzyl alcohol gave the 4-nitrobenzyl glycoside 18, which was converted via reduction of nitro group and N-acylation into the corresponding glycolipid derivative 19. Compounds 14-17 and 19 were transformed into the title compounds by O-deacylation and hydrolysis of methyl ester group in good yields. 相似文献
9.
Makoto Kiso Hideki Katagiri Hiroyasu Furui Keiko Ando Hideharu Ishida Akira Hasegawa 《Journal of carbohydrate chemistry》2013,32(2):163-174
Abstract O-(6-O-Benzoyl-β-d-galactopyranosyl)-(1→4)- and O-(2, 3, 4-tri-O-acetyl-β-d-galactopyranosyl)-(1→4)-2, 3, 6-tri-O-benzyl-N-benzyloxycarbonyl-1, 5-dideoxy-1, 5-imino-d-glucitols (4 and 12) were each coupled with methyl (methyl 5-acetamido-4, 7, 8, 9-tetra-O-acetyl-3, 5-dideoxy-2-thio-d-glycero-d-galacto-2-nonulopyranosid)onate (5) in acetonitrile medium in the presence of dimethyl(methylthio)sulfonium triflate (DMTST) or N-iodosuccinimide/trifluoromethanesulfonic acid to give the corresponding α-sialyl-(2 → 3)- and α-sialyl-(2 → 6)-glycosides (6 and 13α), which were converted to novel ganglioside GM3-related trisaccharides (9 and 15) containing N-methyl-1-deoxynojirimycin. 相似文献
10.
A synthesis of N-acetylneuraminic acid ( 1 ) and of N-acetyl-4-epineuraminic acid ( 2 , R = H) from 2-acetamido-4,6-O-benzylidene-1,2-dideoxy-1-nitro-D -mannopyranose ( 3 ) and 2-acetamido-1,2-dideoxy-4,6-O-isopropylidene-1-nitro-D -mannopyranose ( 4 ), respectively, is described. Michael addition of 3 and 4 to tert-butyl 2-(bromomethyl)prop-2-enoate ( 5 ) and subsequent hydrolytic removal of the NO2 group gave the 4-nonulosonate tautomers 6 / 7 and 8 / 9 , respectively (Scheme). Stereoselective reduction of 6 / 7 and 8 / 9 with NaBH4/AcOH in dioxane/H2O yielded 12/13 (94:6) and 14/15 (92:8), respectively. Reduction of 6 / 7 and 8 / 9 in the absence of AcOH or in EtOH gave 12 / 13 (15:85) and 14 / 15 (15:85), respectively. Ozonolysis of 12 and 13 followed by hydrolysis gave tert-butyl neuraminate 22 and tert-butyl 4-epineuraminate 24 , respectively. Ozonolysis of 14 / 15 , separation of the products 20 and 21 , and hydrolytic removal of the isopropylidene groups gave 22 and 24 , respectively. The tert-butyl ester 22 was saponified to give 1 , which was further characterized as the methyl ester 23 . Saponification of 24 gave the crude 4-epimer of 1 , which was converted into the stable Na salt 2 and also into the methyl ester 25 . 相似文献
11.
Kenji Hotta Hideharu Ishida Makoto Kiso Akira Hasegawa 《Journal of carbohydrate chemistry》2013,32(4-5):491-506
Abstract A first total synthesis of a cholinergic neuron-specific ganglioside, GQ1bα (IV3Neu5Acα, III6Neu5Acα, II3Neu5Acα2-Gg4Cer) is described. Regio- and stereo-selective monosialylation of the hydroxyl group at C-6 of the GalNAc residue in 2-(trimethylsilyl)ethyl O-(2-acetamido-2-deoxy-3,4-O-isopropylidene-β-d-galactopyranosyl)-(1→4)-O-(2,6-di-O-benzyl-β-dgalactopyranosyl)-(1→4)- O-2,3,6-tri-O-benzyl-β-dglucopyranoside (4) with methyl (phenyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-d glycero-d galacto-2-nonulopyranosid) onate (5), and subsequent dimericsialylation of the hydroxyl group at C-3 of the Gal residue with methyl [phenyl 5-acetamido-8-O-(5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-d glycero-α-d galacto-2-nonulopyranosylono-1′,9-lactone)-4, 7-di-O-acetyl-3,5-dideoxy-2-thio-d glycero-d galacto-2-nonulopyranosid]onate (7), using N-iodosuccinimide (NIS)-trifluoromethanesulfonic acid (TfOH) as a promoter, gave the desired hexasaccharide 8 containing α-glycosidically-linked mono- and dimeric sialic acids. This was transformed into the acceptor 9 by removal of the isopropylidene group. Condensation of methyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-d glycero-α-d galacto-2-nonulopyranosylonate)-(2→3)-2,4,6-tri-O-benzoyl-1-thio-β-dgalactopyranoside (10) with 9, using dimethyl(methylthio)sulfonium triflate (DMTST) as a promoter, gave the desired octasaccharide derivative 11 in high yield. Compound 11 was converted into α-trichloroacetimidate 14, via reductive removal of the benzyl groups, O-acetylation, removal of the 2-(trimethylsilyl)ethyl group, and treatment with trichloroacetonitrile, which, on coupling with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (15), gave the β-glycoside 16. Finally, 16 was transformed, via selective reduction of the azido group, coupling with octadecanoic acid, O-deacylation, and hydrolysis of the methyl ester group, into the title ganglioside 18 in good yield. 相似文献
12.
Kenji Hotta Shiro Komba Hideharu Ishida Makoto Kiso Akira Hasegawa 《Journal of carbohydrate chemistry》2013,32(5):665-677
Abstract A stereocontrolled synthesis of α-series ganglioside GM1α (III6Neu5AcGgOse4Cer) is described. Glycosylation of 2-(trimethylsilyl)ethyl O-(2,3,6-tri-O-benzyl-β-d-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-β-d-glucopyranoside (1) with the suitably protected galactosamine donor, methyl 3-O-acetyl-4,6-O-benzylidene-2-deoxy-2-phthalimido-1-thio-β-d-galactopyranoside (4) gave the desired trisaccharide, which was transformed into the trisaccharide acceptor via removal of the phthaloyl and O-acetyl groups followed by N-acetylation. Glycosylation of this acceptor with methyl 3-O-benzyl-2,4,6-tri-O-benzoyl-1-thio-β-d-galactopyranoside (7) gave the asialo GM1 saccharide derivative, which was transformed into the acceptor by removal of benzylidene group. Coupling of this gangliotetraose acceptor with phenyl (methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-d-glcero-d-galacto-2-nonulopyranosyl)onate by use of NIS-TfOH afforded the desired GM1α oligosaccharide derivative in high yield, which was transformed, via removal of the benzyl group followed by O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group and subsequent imidate formation, into the final glycosyl donor. Condensation of this imidate derivative with (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (15) gave the β-glycoside, which on channeling through selective reduction of azido group, coupling of the amino group with octadecanoic acid, O-deacylation and saponification of the methyl ester group, gave the title compound GM1α. 相似文献
13.
Akihiko Kameyama Hideharu Ishida Makoto Kiso Akira Hasegawa 《Journal of carbohydrate chemistry》2013,32(5):641-654
Abstract The first total synthesis of tumor-associated glycolipid antigen, sialyl Lea, is described. Methylsulfenyl bromide-silver triflate-promoted coupling of 2-(trimethylsilyl)ethyl O-(2-acetamido-6-O-benzyl-2-deoxy-β-d-glucopyranosyl)-(1→3)-O-(2,4,6-tri-O-benzyl-β-d-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-β-d-glucopyranoside (2) with methyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-d-glycero-α-d-galacto-2-nonulopyranosylonate)-(2→3)-2,4,6-tri-O-benzoyl-1-thio-β-d-galactopyranoside (3) afforded the pentasaccharide 4a and 5a in good yields. Glycosylation of 4a with methyl 2,3,4-tri-O-benzyl-1-thio-β-l-fucopyranoside (6) by use of N-iodosuccinimide (NIS) — trifluoromethanesulfonic acid (TfOH) as a promoter, gave the desired hexasaccharide 7. Compound 7 was converted into the α-trichloroacetimidate 10, via reductive removal of benzyl groups, O-acetylation, removal of the 2-(trimethylsilyl)ethyl group, and treatment with trichloroacetonitrile, which, on coupling with (2S, 3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1, 3-diol (11), gave the β-glycoside 12. Finally, 12 was transformed, via selective reduction of the azide group, coupling with octadecanoic acid, O-deacylation, and hydrolysis of the methyl ester group, into the title ganglioside 15 in good yield. 相似文献
14.
Kenji Hotta Hideharu Ishida Makoto Kiso Akira Hasegawa 《Journal of carbohydrate chemistry》2013,32(2):175-191
Abstract A stereocontrolled synthesis of I-active ganglioside analog is described. Glycosylation of 2-(trimethylsilyl)ethyl O-(2-O-benzyl-4,6-O-benzylidene-β-d-galactopyranosyl)-(1 → 4)-2,3,6-tri-O-benzyl-β-d-glucopyranoside (5) with methyl 4-O-acetyl-1,6-di-O-benzyl-2-deoxy-2-phthalimido-1-thio-β-d-glucopyranoside (10) by use of N-iodosuccinimide (NIS)-trifluoromethanesulfonic acid (TfOH) gave the desired trisaccharide 11, which was transformed into trisaccharide acceptor 14 via removal of the phthaloyl group followed by N-acetylation, and debenzylidenation. Glycosylation of 14 with methyl 3-O-benzyl-4,6-O-benzylidene-2-deoxy-2-phthalimido-1-thio-β-d-glucopyranoside (8) gave the biantennary compound 15, which was transformed into the acceptor 16. Dimethyl(methylthio)sulfonium triflate (DMTST)-promoted coupling of 16 with methyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-d-glycero-α-d-galacto-2-nonulopyranosylonate)-(2→3)-2,4,6-tri-O-benzoyl-1-thio-β-d-galactopyranoside (17) afforded the desired hexasaccharide 19. Coupling of the hexasaccharide acceptor 20, prepared from 19 by reductive ring-opening of benzylidene acetal, with 17 gave octasaccharide derivative 21. Compound 21 was transformed, via removal of the benzyl group followed by O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group and subsequent imidate formation, into the final glycosyl donor 24. Condensation of 24 with (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (18) gave the β-glycoside 25, which on channeling through selective reduction of azido group, coupling of the amino group with octadecanoic acid, O-deacylation and saponification of the methyl ester group, gave the title compound 28. 相似文献
15.
Yukihiro Isogai Tomoko Kawase Hideharu Ishida Makoto Kiso Akira Hasegawa 《Journal of carbohydrate chemistry》2013,32(8):1001-1023
ABSTRACT 3-O-Sulfo glucuronyl paragloboside derivatives (pentasaccharides) have been synthesized. The important intermediate designed for a facile sulfation in the last step and effective, stereocontrolled glycosidation, methyl (4-O-acetyl-2-O-benzoyl-3-O-levulinoyl-α-D-glucopyranosyl trichloroacetimidate)uronate (8) was prepared from methyl [2-(trimethylsilyl)ethyl β-D-glucopyranosid]uronate (3) via selective 4-O-acetylation, 2-O-benzoylation, 3-O-levulinoylation, removal of the 2-(trimethylsilyl)ethyl group and imidate formation. The glycosylation of 8 with 2-(trimethylsilyl)ethyl 2,4,6-tri-O-benzyl-β-D-galactopyranoside (9) using trimethylsilyl trifluoromethanesulfonate gave 2-(trimethylsilyl)ethyl O-(methyl 4-O-acetyl-2-O-benzoyl-3-O-levulinoyl-β-D-glucopyranosyluronate)-(1→3)-2,4,6-tri-O-benzyl-β-D-galactopyranoside (10), which was transformed via removal of the benzyl group, benzoylation, removal of the 2-(trimethylsilyl)ethyl group and imidate formation into the disaccharide donor 13. On the other hand, 2-(trimethylsilyl)ethyl O-(2-acetamido-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranosyl)-(1→3)-O-(2,4,6-tri-O-benzyl-β-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-β-D-glucopyranoside (20) as the acceptor was prepared from 2-(trimethylsilyl)ethyl 3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranoside (14) via O-acetylation, removal of the 2-(trimethylsilyl)ethyl group, imidate formation, coupling with 2-(trimethylsilyl)ethyl O-(2,4,6-tri-O-benzyl-β-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-β-D-glucopyranoside (18), removal of the O-acetyl and N-phthaloyl group followed by N-acetylation. Condensation of 13 with 20 using trimethylsilyl trifluoromethanesulfonate afforded the desired pentasaccharide 21, which was transformed by removal of the benzyl group, O-acetylation, removal of the 2-(trimethylsilyl)ethyl group and imidate formation into the pentasaccharide donor 24. Glycosylation of (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (25) with 24 gave the desired β-glycoside 26, which was transformed into the four target compounds, via reduction of the azido group, coupling with octadecanoic acid or tetracosanoic acid, selective removal of the levulinoyl group, O-sulfation, hydrolysis of the methyl ester group and O-deacylation. 相似文献
16.
Akira Hasegawa Yukiyasu Ito Minoru Morita Hideharu Ishida Makoto Kiso 《Journal of carbohydrate chemistry》2013,32(1):135-144
Abstract 5-Acetamido-3.5-dideoxy-D-galacto-2-octulosonic acid derivatives and the α-2-thioanalog (14) were synthesized. Methyl [2-(trimethylsilyl)ethyl 5-acetamido-3,5-dideoxy-α-D-galacto-2-octulopyranosid]onate (8), prepared from methyl [2-(trimethylsilyl)ethyl 5-acetamido-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosid]onate (1) via 8,9-O-isopropylidenation, O-acetylation, O-deisopropylidenation, metaperiodate oxidation, and sodium borohydride reduction, was converted, by selective bromination, into the 8-bromo derivatives (9). Compound 12, derived from 8 via O-acetylation and boron trifluoride etherate treatment, was converted to the 2-chloro derivative (13), which underwent displacement with potassium thioacetate, to yield methyl 5-acetamido-4,7,8-tri-O-acetyl-2-S-acetyl-2-thio-α-D-galacto-2-octulopyranosonate (14). 相似文献
17.
《Journal of carbohydrate chemistry》2013,32(6):431-440
An unexpected epimerization resulting from the reaction of α-D-glucopyranosyl derivatives with DAST is described. The reaction of 3,4-di-O-acetyl-1,6-di-O-trityl-β-D-fructofuranosyl 2,3,6-tri-O-acetyl-α-D-glucopyranoside (1), methyl 2,3-di-O-acetyl-6-O-trityl-α-D-glucopyranoside (6), 2,3-di-O-acetyl-6-O-trityl-α-D-glucopyranosyl 2,3-di-O-acetyl-6-O-trityl-α-D-glucopyranoside (13), and 2,3-di-O-acetyl-6-O-tert-butyldiphenylsilyl-α-D-glucopyranosyl 2,3,4,6-tetra-O-acetyl-α-D-glucopyranoside (14) with DAST at 0°C did not give the expected C-4 fluorodeoxy galacto derivatives, but instead, the corresponding 4-O-acetyl-3-hydroxy-α-D-galactopyranosides in yields of 52–78%. When the treatment of 6 was carried out at ?25°C for ~5 min the corresponding diastereomeric 4-O-diethylaminosulfinates (9a,b) were isolated as the major products (40%). Evidence suggests that the epimerization reaction most probably resulted from an intramolecular displacement of the intermediate diethylaminosulfur difluoride ester or diethylaminosulfinyl ester by the neighbouring acetoxy groups. 相似文献
18.
Hideki Ishida Hideharu Ishida Makoto Kiso Akira Hasegawa 《Journal of carbohydrate chemistry》2013,32(5):655-664
Abstract α-Stereocontrolled, glycoside synthesis of trimeric sialic acid is described toward a systematic approach to the synthesis of sialoglycoconjugates containing an α-sialyl-(2→8)-α-sialyl-(2→8)-sialic acid unit α-glycosidically linked to O-3 of a galactose residue in their oligosaccharide chains. Glycosylation of 2-(trimethylsilyl)ethyl 6-O-benzoyl-β-d-galactopyranoside (4) or 2-(trimethylsilyl)ethyl 2,3,6,2′,6′-penta-O-benzyl-β-lactoside (5), with methyl [phenyl 5-acetamido-8-O-[5-acetamido-8-O-(5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-d-glycero-α-d-galacto-2-nonulopyranosylono-1”, 9′-lactone)-4,7-di-O-acetyl-3,5-dideoxy-d-glycero-α-d-galacto-2-nonulopyranosylono-1′, 9-lactone]-4,7-di-O-acetyl-3,5-dideoxy-2-thio-d-glycero-d-galacto-2-nonulopyranosid]onate (3), using N-iodosuccinimide-trifluoromethanesulfonic acid as a promoter, gave the corresponding α-glycosides 6 and 8, respectively. The glycosyl donor 3 was prepared from trimeric sialic acid by treatment with Amberlite IR-120 (H+) resin in methanol, O-acetylation, and subsequent replacement of the anomeric acetoxy group with phenylthio. Compounds 6 and 8 were converted into the per-O-acyl derivatives 7 and 9, respectively. 相似文献
19.
Akira Hasegawa Takao Nagahama Hitoshi Ohki Makoto Kiso 《Journal of carbohydrate chemistry》2013,32(6):699-714
Abstract A stereocontrolled, facile total synthesis of ganglioside GM2 is described. Coupling of 2- (trimethylsilyl)ethyl O-(2,6-di-O-benzyl-(β-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-β-D-glucopyranoside (2), prepared from 2-(trimethylsilyl)ethyl β-lactoside (1) by selective 3′,4′-O-isopropylidenation, O-benzylation, and subsequent removal of the isopropylidene group, with methyl (methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy -2-thio-D-glycero-D-galacto -2-nonulopyranosid)onate (4) using N-iodosuccini-midc (NIS), gave the trisaccharide (5), which on condensation with methyl 6-O-benzoyl -2-dcoxy-3,4-O-isopropylidene-2-phthalimido-l-thio-β-D-galactopyranoside (11), gave the protected ganglioside GM2 oligosaccharide 12. Compound 12 was transformed, via O-deisopropylidenation, O-acetylation, removal of the phthaloyl group, N-acetylation, removal of the benzyl groups followed by (O-acetylation, selective removal of the 2-(rximethylsilyl)ethyl group, and subsequent imidate formation, into the final glycosyl donor 19. Glycosylation of (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-l,3-diol (20) with the α-trichloroacetimidate 19 gave the β-glycoside 21, which on channeling through selective reduction of the azide group, coupling of the amino group with octadecanoic acid, O-deacylation and saponification of the methyl ester group, gave the title ganglioside. 相似文献
20.
The phosphonic acids 3 and 4 were prepared to compare their inhibitory activity on Vibrio cholerae sialidase with the one of the corresponding N-acetyl-2-deoxyneuraminic acids 5 and 6 . Thus, hydrogenation and benzylation of methyl N-acetyl-2,3-didehydro-2-deoxyneuraminate (1MeNeu2en5Ac; 7) gave a mixture of the fully O-benzylated benzyl and methyl esters 9 and 10 , the partially O-benzylated benzyl and methyl esters 11 and 12 , and the fully O-and N-benzylated benzyl and methyl esters 13 and 14 (Scheme 1). Transesterification of 9 to 10 and hydrolysis of 10 gave the acid 15 . Oxidative decarboxylation of 15 with Pb(OAc)4 gave a 1:9 mixture of the α-and β-D-glycero-D-galacto-acetates 16 and 17 . Phosphonoylation of 17 with P(OMe)3 and Me3SiOTf gave a 1.3:1 mixture of the phosphonates 18 and 19 , which were deprotected to give the (4-acetamido-2,4-dideoxy-D-glycero-α-and β-D-galacto-octopyranosyl)phosphonic acids 3 and 4 , respectively. The acid 6 was obtained by epimerization of the tert-butyl ester 23 with lithium N-cyclohexylisoproylamide and deprotection. The phosphonic acids 3 (Ki 5.5 10-5 M) and 4 (Ki 2.3.10?4 M ) are stronger inhibitors of Vibrio cholerae sialidase than the anomeric N-acetyl-2-deoxyneuraminic acids 5 (Ki 2.3 10?3 M ) and 6 . Both 3 and 4 inhibit the Vibrio cholerae sialidase, while only the carboxylic acid 5 , possessing an equatorial COOH group is an inhibitor. 相似文献