(1→6)-β-D-吡喃半乳糖寡糖的2,3-环氧丙基β-糖苷的合成及其与抗半乳聚糖单克隆IgA J539和IgA X24的结合

Synthesis of 2,3-epoxypropyl beta-glycosides of (1----6)-beta-D-galactopyranooligosaccharides and their binding to monoclonal anti-galactan IgA J539 and IgA X24.

作者信息

Nashed E M, Glaudemans C P

出版信息

Carbohydr Res. 1986 Dec 15;158:125-36. doi: 10.1016/0008-6215(86)84011-3.

Abstract

Reaction of 2,3,4-tri-O-acetyl-6-O-(bromoacetyl)-alpha-D-galactopyranosyl bromide (2) with allyl 2,3,4-tri-O-acetyl-beta-D-galactopyranoside gave allyl O-[2,3,4-tri-O-acetyl-6-O-(bromoacetyl)-alpha- and -beta-D-galactopyranosyl]-(1----6)-2,3,4-tri-O-acetyl-beta-D- galactopyranoside, 4 (4%) and 5 (88%), respectively. Selective removal of the bromoacetyl group from 5 gave allyl O-(2,3,4-tri-O-acetyl-beta-D-galactopyranosyl)-(1----6)-2,3,4-tri-O-a cet yl-beta - D-galactopyranoside (6), which, after condensation with 2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl bromide (1) yielded both allyl O-(2,3,4,6-tetra-O-acetyl-alpha- and -beta-D-galactopyranosyl)-(1----6)-O-(2,3,4-tri-O-acetyl-beta-D- galactopyranosyl)-(1----6)-2,3,4-tri-O-acetyl-beta-D-galactopyranoside, 7 (10%) and 8 (70%), respectively. When 6 was condensed with 2, allyl O-[2,3,4-tri-O-acetyl-6-O-(bromoacetyl)-beta-D-galactopyranosyl]-(1----6 )-O- (2,3,4-tri-O-acetyl-beta-D-galactopyranosyl)-(1----6)-2,3,4-tri-O-acetyl -beta-D - galactopyranoside (75%) was obtained. This was selectively O-de(bromoacetyl)ated to yield the nonaacetate, which was condensed with bromide 1 to give allyl O-(2,3,4,6-tetra-O-acetyl-alpha- and -beta-D-galactopyranosyl)-(1----6)-O-(2,3,4-tri-O-acetyl-beta-D- galactopyranosyl)-(1----6)-O-(2,3,4-tri-O-acetyl-beta-D-galactopyranosyl )- (1----6)-2,3,4-tri-O-acetyl-beta-D-galactopyranoside, 14 (4%) and 15 (70%). Epoxidation of the allyl group of 8 and 15 with m-chloroperoxybenzoic acid, and removal of the acetyl protecting groups with sodium methoxide, gave, respectively, 2,3-epoxypropyl O-beta-D-galactopyranosyl-(1----6)-O-beta-D-galactopyranosyl-(1----6)-be ta-D- galactopyranoside (17) and the corresponding tetrasaccharide 19. Sequential acetylation and O-debenzylation of 6-O-benzyl-D-galactose, followed by coupling of the product with bromide 1, yielded O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-(1----6)-1,2,3,4-tetr a-O- acetyl-beta-D-galactopyranose (12). Conversion of 12 into the bromide by treatment with bromotrimethylsilane, and condensation of the product with nucleophile 6 also gave the beta-linked tetrasaccharide 15 of this series. Epoxidation of the allyl group, followed by removal of acetyl blocking groups in the latter compound, again gave 2,3-epoxypropyl O-beta-D-galactopyranosyl-(1----6)-O-beta-D-galactopyranosyl-(1----6)-O- beta-D- galactopyranosyl-(1----6)-beta-D-galactopyranoside (19).(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

2,3,4-三-O-乙酰基-6-O-(溴乙酰基)-α-D-吡喃半乳糖基溴(2)与烯丙基2,3,4-三-O-乙酰基-β-D-吡喃半乳糖苷反应，分别得到烯丙基O-[2,3,4-三-O-乙酰基-6-O-(溴乙酰基)-α-和-β-D-吡喃半乳糖基]-(1→6)-2,3,4-三-O-乙酰基-β-D-吡喃半乳糖苷，4(4%)和5(88%)。从5中选择性除去溴乙酰基得到烯丙基O-(2,3,4-三-O-乙酰基-β-D-吡喃半乳糖基)-(1→6)-2,3,4-三-O-乙酰基-β-D-吡喃半乳糖苷(6)，其与2,3,4,6-四-O-乙酰基-α-D-吡喃半乳糖基溴(1)缩合后，分别得到烯丙基O-(2,3,4,6-四-O-乙酰基-α-和-β-D-吡喃半乳糖基)-(1→6)-O-(2,3,4-三-O-乙酰基-β-D-吡喃半乳糖基)-(1→6)-2,3,4-三-O-乙酰基-β-D-吡喃半乳糖苷，7(10%)和8(70%)。当6与2缩合时，得到烯丙基O-[2,3,4-三-O-乙酰基-6-O-(溴乙酰基)-β-D-吡喃半乳糖基]-(1→6)-O-(2,3,4-三-O-乙酰基-β-D-吡喃半乳糖基)-(1→6)-2,3,4-三-O-乙酰基-β-D-吡喃半乳糖苷(75%)。将其选择性地进行O-脱(溴乙酰基)化得到九乙酸酯，该九乙酸酯与溴化物1缩合，得到烯丙基O-(2,3,4,6-四-O-乙酰基-α-和-β-D-吡喃半乳糖基)-(1→6)-O-(2,3,4-三-O-乙酰基-β-D-吡喃半乳糖基)-(1→6)-O-(2,3,4-三-O-乙酰基-β-D-吡喃半乳糖基)-(1→6)-2,3,4-三-O-乙酰基-β-D-吡喃半乳糖苷，14(4%)和15(70%)。用间氯过氧苯甲酸将8和15的烯丙基环氧化，并用甲醇钠除去乙酰保护基，分别得到2,3-环氧丙基O-β-D-吡喃半乳糖基-(1→6)-O-β-D-吡喃半乳糖基-(1→6)-β-D-吡喃半乳糖苷(17)和相应的四糖19。6-O-苄基-D-半乳糖依次进行乙酰化和O-脱苄基化，然后将产物与溴化物1偶联，得到O-(2,3,4,6-四-O-乙酰基-β-D-吡喃半乳糖基)-(1→6)-1,2,3,4-四-O-乙酰基-β-D-吡喃半乳糖(12)。用溴化三甲基硅烷处理将12转化为溴化物，产物与亲核试剂6缩合也得到该系列的β-连接的四糖15。烯丙基环氧化，然后除去后一种化合物中的乙酰保护基，再次得到2,3-环氧丙基O-β-D-吡喃半乳糖基-(1→6)-O-β-D-吡喃半乳糖基-(1→6)-O-β-D-吡喃半乳糖基-(1→6)-β-D-吡喃半乳糖苷(19)。(摘要截断于400字)