Synthesis of lacto-N-neotetraose and lacto-N-tetraose using the dimethylmaleoyl group as amino protective group
Synthesis of lacto-N-neotetraose and lacto-N-tetraose using the dimethylmaleoyl group as amino protective group
复制标题
DOI：
10.1016/s0008-6215(99)00051-8
复制
发表时间：
1999-03-31
影响因子：
3.1
通讯作者：
Schmidt, RR
中科院分区：
文献类型：
--
作者：
Aly, MRE;Ibrahim, ESI;Schmidt, RR
二糖供体O-[2，3，4，6-四-O-乙酰基-β-D-吡喃半乳糖基）-（1-→ 4）-3，6-二-O-苄基-2-脱氧-2-二甲基马来酰亚胺基-α，β-D-吡喃葡萄糖基]三氯乙酰亚氨酸酯（7）通过使O-（2，3，4，6-四-O-乙酰基-α-D-吡喃半乳糖基）三氯乙酰亚胺酯与叔丁基二甲基甲硅烷基3，6-二-O-苄基-2-脱氧-2-二甲基马来酰氨基-吡喃葡萄糖苷，得到相应的二糖5。将异头中心脱保护，然后与三氯乙腈反应，得到7。7与3 '-O-未保护的苄基的反应作为受体的（2，4，6-三-O-苄基-β-D-半乳糖基）-（1->4 4）-2，3，6-三-O-苄基-β-D-葡萄糖吡喃苷（8）得到所需的四糖苄基（2，3，4，6-tetra-O-acetyl-beta-D-galactopyranosyl）-（1->4）-（3，6-二-O-苄基-2-脱氧-2-二甲基马来酰亚胺-β-D-吡喃葡萄糖基）-（1->3）-（2，4，6-三-O-苄基-β-D-吡喃半乳糖基）-（1->4）-2，3，6-三-O-苄基-β-D-吡喃葡萄糖苷。N-二甲基马来酰基被乙酰基取代，O-脱苄基，最后O-脱乙酰基得到乳糖-N-新四糖。同样，O-[（2，3，4，6-四-O-乙酰基-β-D-吡喃半乳糖基）-（1-→ 3）-4，6-O-亚苄基-2-脱氧-2-二甲基马来酰亚胺基-α，β-D-吡喃葡萄糖基]三氯乙酰亚胺酯作为供体，8作为受体，得到所需的四糖苄基（2，3，4，6-tetra-O-acetyl-beta-D-galactopyranosyl）-（1-->3）-（4，6-亚苄基-2-脱氧-2-二甲基马来酰亚胺-β-D-吡喃葡萄糖基）-（1->3）-（2，4，6-三-O-苄基-β-D-吡喃半乳糖基）-（1->4）-2，3，6-三-O-苄基-β-D-吡喃葡萄糖苷。除去亚苄基，用乙酰基取代N-二甲基马来酰基，然后O-乙酰化，得到四糖中间体15，其仅携带O-苄基和O-乙酰基保护基。O-脱苄基和O-脱乙酰基得到乳糖-N-四糖（1）。另外，已知的叔丁基二甲基甲硅烷基将（2，3，4，6-四-O-乙酰基-β-D-吡喃半乳糖基）-（1->3）-4，6-O-亚苄基-2-脱氧-2-二甲基马来酰亚胺基-β-D-吡喃半乳糖苷转化为O-[2，3，4，6-四-O-乙酰基-β-D-吡喃半乳糖基）-（1->3）-4，6-二-O-乙酰基-2-脱氧-2-二甲基马来酰亚胺基-α，β-D-吡喃葡萄糖基]三氯乙酰亚氨酸酯作为糖基供体，以8作为受体，得到相应的四糖22，将其转化为15，从而得到1的替代方法。(C)1999爱思唯尔科技有限公司。保留所有权利。
The disaccharide donor O-[2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-(1-->4)-3,6-di-O-benzyl-2-deoxy-2-dimethylmaleimido-alpha,beta-D-glucopyranosyl] trichloroacetimidate (7) was prepared by reacting O-(2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl) trichloroacetimidate with tert-butyldimethylsilyl 3,6-di-O-benzyl-2-deoxy-2-dimethylmaleoylamido-glucopyranoside to give the corresponding disaccharide 5. Deprotection of the anomeric center and then reaction with trichloroacetonitrile afforded 7. Reaction of 7 with 3'-O-unprotected benzyl (2,4,6-tri-O-benzyl-beta-D-galactopyranosyl)-(1-->4 4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside (8) as acceptor afforded the desired tetrasaccharide benzyl (2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-(1-->4)-(3,6-di-O-benzyl-2-deoxy-2-dimethylmaleimido-beta-D-glucopyranosyl)-(1-->3)-(2,4,6-tri-O-benzyl-beta-D-galactopyranosyl)-(1-->4)-2,3,6-tri-O-benzyl-beta-D-glucopyranosid. Replacement of the N-dimethylmaleoyl group by the acetyl group, O-debenzylation and finally O-deacetylation gave lacto-N-neotetraose. Similarly, reaction of O-[(2,3,4,6-tetra-O-acetyl-beta-D-galactopyraonsyl)-(1-->3)-4,6-O-benzylidene-2-deoxy-2-dimethylmaleimido-alpha,beta-D-glycopyranosyl] trichloroacetimidate as donor with 8 as acceptor afforded the desired tetrasaccharide benzyl (2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-(1-->3)-(4,6-benzylidene-2-deoxy-2-dimethylmaleimido-beta-D-glucopyranosyl)-(1-->3)-(2,4,6-tri-O-benzyl-beta-D-galactopyranosyl)-(1-->4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside. Removal of the benzylidene group, replacement of the N-dimethylmaleoyl group by the acetyl group and then O-acetylation afforded tetrasaccharide intermediate 15, which carries only O-benzyl and O-acetyl protective groups. O-Debenzylation and O-deacetylation gave lacto-N-tetraose (1). Additionally, known tert-butyldimethylsilyl (2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-(1-->3)-4,6-O-benzylidene-2-deoxy-2-dimethylmaleimido-beta-D-galactopyranoside was transformed into O-[2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-(1-->3)-4,6-di-O-acetyl-2-deoxy-2-dimethylmaleimido-alpha,beta-D-glucopyranosyl] trichloroacetimidate as glycosyl donor, to afford with 8 as acceptor the corresponding tetrasaccharide 22, which is transformed into 15, thus giving an alternative approach to 1. (C) 1999 Elsevier Science Ltd. All rights reserved.