23F型肺炎链球菌荚膜多糖含间隔区重复单元的合成

Synthesis of a spacer-containing repeating unit of the capsular polysaccharide of Streptococcus pneumoniae type 23F.

作者信息

van Steijn A M, Kamerling J P, Vliegenthart J F

机构信息

Department of Bio-Organic Chemistry, Utrecht University, The Netherlands.

出版信息

Carbohydr Res. 1991 Apr 24;211(2):261-77. doi: 10.1016/0008-6215(91)80096-6.

DOI:10.1016/0008-6215(91)80096-6

PMID:1769015

Abstract

The synthesis is reported of 3-aminopropyl 4-O-(4-O-beta-D-glucopyranosyl-2-O-alpha-L-rhamnopyranosyl-beta-D- galactopyranosyl)-beta-L-rhamnopyranoside 3'-(glycer-2-yl sodium phosphate) (25 beta), which represents the repeating unit of the capsular polysaccharide of Streptococcus pneumoniae type 23F (American type 23) [(----4)-beta-D-Glcp-(1----4)-[Glycerol-(2-P----3)] [alpha-L- Rhap-(1----2)]-beta-D-Galp-(1----4)-beta-L-Rhap-(1----)n). 2,4,6-Tri-O-acetyl-3-O-allyl-alpha-D-galactopyranosyl trichloroacetimidate (5) was coupled with ethyl 2,3-di-O-benzyl-1-thio-alpha-L-rhamnopyranoside (6). Deacetylation of the resulting disaccharide derivative, followed by benzylidenation, and condensation with 2,3,4-trio-O-acetyl-alpha-L-rhamnopyranosyl trichloroacetimidate (10) afforded ethyl 4-O-[3-O-allyl-4,6-O-benzylidene-2-O-(2,3,4-trio-O-acetyl- alpha-L-rhamnopyranosyl)-beta-D-galactopyranosyl]-2,3-di-O-benzyl-1-thio - alpha-L-rhamnopyranoside (11). Deacetylation of 11, followed by benzylation, selective benzylidene ring-opening, and coupling with 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl trichloroacetimidate (15) gave ethyl 4-O-[3-O-allyl-6-O-benzyl-4-O-(2,3,4,6- tetra-O-acetyl-beta-D-glucopyranosyl)-2-O-(2,3,4-tri-O-benzyl-alpha-L- rhamnopyranosyl)-beta-D-galactopyranosyl]-2,3-di-O-benzyl-1-thio-alpha-L - rhamnopyranoside (16). Deacetylation of 16 followed by benzylation, deallylation, and acetylation yielded ethyl 4-O-[3-O-acetyl-6-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-beta-D-glucopy ran osyl)- 2-O-(2,3,4-tri-O-benzyl-alpha-L-rhamnopyranosyl)-beta-D-galactopyranosyl ]-2,3- di-O-benzyl-1-thio-alpha-L-rhamnopyranoside (20). The glycosyl bromide derived from 20, when coupled with 3-benzyloxycarbonylamino-1-propanol, gave the beta-glycoside (21 beta) as the major product. Deacetylation of 21 beta followed by condensation with 1,3-di-O-benzylglycerol 2-(triethylammonium phosphonate) (27), oxidation, and deprotection, afforded 25 beta.

摘要

报道了3-氨基丙基4-O-(4-O-β-D-吡喃葡萄糖基-2-O-α-L-吡喃鼠李糖基-β-D-吡喃半乳糖基)-β-L-吡喃鼠李糖苷3'-(甘油-2-基磷酸钠)(25β)的合成，它代表肺炎链球菌23F型(美国23型)荚膜多糖的重复单元[(----4)-β-D-葡萄糖-(1----4)-[甘油-(2-P----3)][α-L-鼠李糖-(1----2)]-β-D-半乳糖-(1----4)-β-L-鼠李糖-(1----)n]。2,4,6-三-O-乙酰基-3-O-烯丙基-α-D-吡喃半乳糖基三氯乙酰亚胺酯(5)与2,3-二-O-苄基-1-硫代-α-L-吡喃鼠李糖苷(6)偶联。所得二糖衍生物脱乙酰化，接着进行亚苄基化，并与2,3,4-三-O-乙酰基-α-L-吡喃鼠李糖基三氯乙酰亚胺酯(10)缩合，得到乙基4-O-[3-O-烯丙基-4,6-O-亚苄基-2-O-(2,3,4-三-O-乙酰基-α-L-吡喃鼠李糖基)-β-D-吡喃半乳糖基]-2,3-二-O-苄基-1-硫代-α-L-吡喃鼠李糖苷(11)。11脱乙酰化，接着进行苄基化、选择性亚苄基环开裂，并与2,3,4,6-四-O-乙酰基-α-D-吡喃葡萄糖基三氯乙酰亚胺酯(15)偶联，得到乙基4-O-[3-O-烯丙基-6-O-苄基-4-O-(2,3,4,6-四-O-乙酰基-β-D-吡喃葡萄糖基)-2-O-(2,3,4-三-O-苄基-α-L-吡喃鼠李糖基)-β-D-吡喃半乳糖基]-2,3-二-O-苄基-1-硫代-α-L-吡喃鼠李糖苷(16)。16脱乙酰化，接着进行苄基化、脱烯丙基化和乙酰化，得到乙基4-O-[3-O-乙酰基-6-O-苄基-4-O-(2,3,4,6-四-O-苄基-β-D-吡喃葡萄糖基)-2-O-(2,3,4-三-O-苄基-α-L-吡喃鼠李糖基)-β-D-吡喃半乳糖基]-2,3-二-O-苄基-1-硫代-α-L-吡喃鼠李糖苷(20)。由20衍生的糖基溴与3-苄氧羰基氨基-1-丙醇偶联时，得到β-糖苷(21β)作为主要产物。21β脱乙酰化，接着与1,3-二-O-苄基甘油2-(三乙铵膦酸酯)(27)缩合、氧化和脱保护，得到25β。