van der Ven J G, Kerékgyártó J, Kamerling J P, Lipták A, Vliegenthart J F
Bijvoet Center, Department of Bio-Organic Chemistry, Utrecht University, Netherlands.
Carbohydr Res. 1994 Nov 1;264(1):45-62. doi: 10.1016/0008-6215(94)00187-1.
The synthesis is reported of methyl 2-acetamido-4-O-[2-acetamido-2-deoxy-O-(3,6-di-O-alpha-D- mannopyranosyl-2-O-beta-D-xylopyranosyl-beta-D-mannopyranosyl)-beta-D- glucopyranosyl]-2-deoxy-beta-D-glucopyranoside (4) and methyl 2-acetamido-4-O-[2-acetamido-2-deoxy-4-O- (3,6-di-O-alpha-D- mannopyranosyl-2-O-beta-D-xylopyranosyl-beta-D-mannopyranosyl)-beta-D- glucopyranosyl]-2-deoxy-6- O-alpha-L-fucopyranosyl-beta-D-glucopyranoside (5), which represent the invariant hexasaccharide core structure of the xylose-containing glycans of N-glycoproteins and its 6-O- fucosylated derivative. Ethyl 4-O-[3-O-allyl-4-O-benzoyl-6-O-tert-butyldimethylsilyl-2-O- (2,3,4-tri-O-acetyl-beta-D-xylopyranosyl)- beta-D-mannopyranosyl]-3,6-di-O-benzyl-2-deoxy-2-phthalimido-1- thio-beta-D-glucopyranoside (9) was coupled with methyl 3,6-di-O-benzyl-2-deoxy-2-phthalimido-beta-D- glucopyranoside (11). Desilylation of the resulting tetrasaccharide derivative, followed by condensation with 2,3,4,6- tetra-O-acetyl-alpha-D-mannopyranosyl trichloroacetimidate (7), gave methyl 4-O-(4-O-[3-O-allyl-4- O-benzoyl-6-O-(2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl)-2-O-(2,3,4 -tri-O- acetyl-beta-D-xylopyranosyl)- beta-D-mannopyranosyl]-3,6-di-O-benzyl-2-deoxy-2-phthalimido-beta-D- glucopyranosyl)- 3,6-di-O-benzyl-2-deoxy-2-phthalimido-beta-D-glucopyranoside (14). Deallylation of 14, followed by condensation with 7 and deprotection, gave hexasaccharide 4. Ethyl 3,6-di-O- benzyl-2-deoxy-4-O- [4,6-di-O-acetyl-3-O-allyl-2-O-(2,3,4-tri-O-acetyl-beta-D-xylopyranosyl) - beta-D-mannopyranosyl]-2- phthalimido-1-thio-beta-D-glucopyranoside (17) was coupled with methyl 3-O- benzyl-2-deoxy-6-O- (4-methoxybenzyl)-2-phthalimido-beta-D-glucopyranoside. Demethoxybenzylation of the tetrasaccharide derivative thus obtained, followed by fucosylation using ethyl 2,3,4-tri-O- benzyl-1-thio- beta-L-fucopyranoside, gave methyl 3-O-benzyl-2-deoxy-4-O-[3,6-di-O-benzyl-2- deoxy-4-O-[4,6- di-O-acetyl-3-O-allyl-2-O-(2,3,4-tri-O-acetyl-beta-D-xylopyranosyl)-beta -D- mannopyranosyl]-2-phthalimido- beta-D-glucopyranosyl)-2-phthalimido-6-O-(2,3,4-tri-O-benzyl-alpha-L- fucopyranosyl)-beta-D-glucopyranoside (23). O-Deacetylation followed by tert-butyldimethylsilylation, benzoylation, and desilylation gave methyl 4-O-(4-O-[3-O-allyl-4-O-benzoyl-2-O-(2,3,4-tri-O-benzoyl-beta-D- xylopyranosyl)- beta-D-mannopyranosyl]-3,6-di-O-benzyl-2-deoxy-2-phthalimido-beta- D-glucopyranosyl)-3- O-benzyl-2-deoxy-2-phthalimido-6-O-(2,3,4-tri-O-benzyl-alpha-L-fucopy ran osyl)- beta-D-glucopyranoside (24). Mannosylation of 24 using 7, followed by deallylation, further mannosylation with 7, and deprotection, gave the heptasaccharide 5.
报道了2-乙酰氨基-4-O-[2-乙酰氨基-2-脱氧-O-(3,6-二-O-α-D-甘露吡喃糖基-2-O-β-D-木吡喃糖基-β-D-甘露吡喃糖基)-β-D-吡喃葡萄糖基]-2-脱氧-β-D-吡喃葡萄糖苷甲酯(4)和2-乙酰氨基-4-O-[2-乙酰氨基-2-脱氧-4-O-(3,6-二-O-α-D-甘露吡喃糖基-2-O-β-D-木吡喃糖基-β-D-甘露吡喃糖基)-β-D-吡喃葡萄糖基]-2-脱氧-6-O-α-L-岩藻糖基-β-D-吡喃葡萄糖苷甲酯(5)的合成，它们代表N-糖蛋白含木糖聚糖的不变六糖核心结构及其6-O-岩藻糖基化衍生物。4-O-[3-O-烯丙基-4-O-苯甲酰基-6-O-叔丁基二甲基甲硅烷基-2-O-(2,3,4-三-O-乙酰基-β-D-木吡喃糖基)-β-D-甘露吡喃糖基]-3,6-二-O-苄基-2-脱氧-2-邻苯二甲酰亚氨基-1-硫代-β-D-吡喃葡萄糖苷乙酯(9)与3,6-二-O-苄基-2-脱氧-2-邻苯二甲酰亚氨基-β-D-吡喃葡萄糖苷甲酯(11)偶联。所得四糖衍生物脱甲硅烷基化，然后与2,3,4,6-四-O-乙酰基-α-D-甘露吡喃糖基三氯乙酰亚胺酯(7)缩合，得到4-O-(4-O-[3-O-烯丙基-4-O-苯甲酰基-6-O-(2,3,4,6-四-O-乙酰基-α-D-甘露吡喃糖基)-2-O-(2,3,4-三-O-乙酰基-β-D-木吡喃糖基)-β-D-甘露吡喃糖基]-3,6-二-O-苄基-2-脱氧-2-邻苯二甲酰亚氨基-β-D-吡喃葡萄糖基)-3,6-二-O-苄基-2-脱氧-2-邻苯二甲酰亚氨基-β-D-吡喃葡萄糖苷甲酯(14)。14脱烯丙基化，然后与7缩合并脱保护，得到六糖4。3,6-二-O-苄基-2-脱氧-4-O-[4,6-二-O-乙酰基-3-O-烯丙基-2-O-(2,3,4-三-O-乙酰基-β-D-木吡喃糖基)-β-D-甘露吡喃糖基]-2-邻苯二甲酰亚氨基-1-硫代-β-D-吡喃葡萄糖苷乙酯(17)与3-O-苄基-2-脱氧-6-O-(4-甲氧基苄基)-2-邻苯二甲酰亚氨基-β-D-吡喃葡萄糖苷甲酯偶联。如此得到的四糖衍生物脱对甲氧基苄基，然后用2,3,4-三-O-苄基-1-硫代-β-L-岩藻糖基乙酯进行岩藻糖基化，得到3-O-苄基-2-脱氧-4-O-[3,6-二-O-苄基-2-脱氧-4-O-[4,6-二-O-乙酰基-3-O-烯丙基-2-O-(2,3,4-三-O-乙酰基-β-D-木吡喃糖基)-β-D-甘露吡喃糖基]-2-邻苯二甲酰亚氨基-β-D-吡喃葡萄糖基)-2-邻苯二甲酰亚氨基-6-O-(2,3,4-三-O-苄基-α-L-岩藻糖基)-β-D-吡喃葡萄糖苷(23)。O-脱乙酰化，然后进行叔丁基二甲基甲硅烷基化、苯甲酰化和脱甲硅烷基化，得到4-O-(4-O-[3-O-烯丙基-4-O-苯甲酰基-2-O-(2,3,4-三-O-苯甲酰基-β-D-木吡喃糖基)-β-D-甘露吡喃糖基]-3,6-二-O-苄基-2-脱氧-2-邻苯二甲酰亚氨基-β-D-吡喃葡萄糖基)-3-O-苄基-2-脱氧-2-邻苯二甲酰亚氨基-6-O-(2,3,4-三-O-苄基-α-L-岩藻糖基)-β-D-吡喃葡萄糖苷(24)。用7对24进行甘露糖基化，然后脱烯丙基化，再用7进一步进行甘露糖基化，最后脱保护，得到七糖5。
