6-O-(2-乙酰氨基-2-脱氧-β-D-吡喃葡萄糖基)-N-乙酰胞壁酰-L-丙氨酰-D-异谷氨酰胺酯的O-乙酰化苄基α-糖苷的合成与反应：肽聚糖相关结构中碱催化的异谷氨酰胺在平衡谷氨酰胺重排中的作用

Synthesis and reactions of O-acetylated benzyl alpha-glycosides of 6-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-N-acetylmuramoyl-L- alanyl-D-isoglutamine esters: the base-catalysed isoglutamine in equilibrium glutamine rearrangement in peptidoglycan-related structures.

作者信息

Keglević D, Derome A E

机构信息

Tracer Laboratory, Department of Organic Chemistry and Biochemistry, Ruder Bosković Institute, Zagreb, Yugoslavia.

出版信息

Carbohydr Res. 1989 Feb 15;186(1):63-75. doi: 10.1016/0008-6215(89)84005-4.

DOI:10.1016/0008-6215(89)84005-4

PMID:2720705

Abstract

Condensation of benzyl 2-acetamido-6-O-(2-acetamido-3,4,6-tri-O-acetyl-2- deoxy-3-O-[(R)-1-carboxyethyl]-alpha-D-glucopyranoside (2) and its 4-acetate (4) with L-alanyl-D-isoglutamine benzyl ester via the mixed anhydride method yielded N-(2-O-[benzyl 2-acetamido-6-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D- glucopyranosyl)-2,3-dideoxy-alpha-D-glucopyranosid-3-yl]-(R)-lacto yl)-L- alanyl-D-isoglutamine benzyl ester (5) and its 4-acetate (6), respectively. Condensation by the dicyclohexylcarbodi-imide-N-hydroxysuccinimide method converted 2 into benzyl 2-acetamido-6-O-(2-acetamido-3,4,6-tri-O-acetyl- 2-deoxy-beta-D-glucopyranosyl)-3-O-[(R)-1-carboxyethyl]-2-deoxy-alpha-D- glucopyranoside 1',4-lactone (7). In the presence of activating agents, 7 underwent aminolysis with the dipeptide ester to give 5. Zemplén O-deacetylation of 5 and 6 led to transesterification and alpha----gamma transamidation of the isoglutaminyl residue to give N-(2-O-[benzyl 2-acetamido-6-O-(2- acetamido-2-deoxy-beta-D-glucopyranosyl)-2,3-dideoxy-alpha-D-glucopyr anosid-3- yl]-(R)-lactoyl)-L-alanyl-D-isoglutamine methyl ester (8) and -glutamine methyl ester (9). Treatment of 6 with MgO-methanol caused deacetylation at the GlcNAc residue to give a mixture of N-(2-O-[benzyl 2-acetamido-6-O-(2-acetamido-2- deoxy-beta-D-glucopyranosyl)-4-O-acetyl-2,3-dideoxy-alpha-D-glucopyra nosid-3- yl]-(R)-lactoyl)-L-alanyl-D-isoglutamine methyl ester (11) and -glutamine methyl ester (12). Benzyl or methyl ester-protection of peptidoglycan-related structures is not compatible with any of the reactions requiring alkaline media. Condensation of 2 with L-alanyl-D-isoglutamine tert-butyl ester gave N-(2-O-[benzyl 2-acetamido- 6-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-glucopyranosyl)-2,3-d ideoxy- alpha-D-glucopyranosid-3-yl]-(R)-lactoyl-L-alanyl-D-isoglutamine tert-butyl ester (16), deacetylation of which, under Zemplén conditions, proceeded without side-reactions to afford N-(2-O-[benzyl 2-acetamido-6-O-(2-acetamido-2-deoxy-beta-D- glucopyranosyl)-2,3-dideoxy-alpha-D-glucopyranosid-3-yl]-(R)-la cotyl)-L- alanyl-D-isoglutamine tert-butyl ester (17).

摘要

通过混合酸酐法使2-乙酰氨基-6-O-(2-乙酰氨基-3,4,6-三-O-乙酰基-2-脱氧-3-O-[(R)-1-羧乙基]-α-D-吡喃葡萄糖苷(2)及其4-乙酸酯(4)与L-丙氨酰-D-异谷氨酰胺苄酯缩合，分别得到N-(2-O-[苄基2-乙酰氨基-6-O-(2-乙酰氨基-3,4,6-三-O-乙酰基-2-脱氧-β-D-吡喃葡萄糖基)-2,3-二脱氧-α-D-吡喃葡萄糖苷-3-基]-(R)-乳酰基)-L-丙氨酰-D-异谷氨酰胺苄酯(5)及其4-乙酸酯(6)。通过二环己基碳二亚胺-N-羟基琥珀酰亚胺法缩合将2转化为苄基2-乙酰氨基-6-O-(2-乙酰氨基-3,4,6-三-O-乙酰基-2-脱氧-β-D-吡喃葡萄糖基)-3-O-[(R)-1-羧乙基]-2-脱氧-α-D-吡喃葡萄糖苷1',4-内酯(7)。在活化剂存在下，7与二肽酯进行氨解反应得到5。5和6的泽普伦O-脱乙酰化导致异谷氨酰胺残基的酯交换和α----γ转酰胺化，得到N-(2-O-[苄基2-乙酰氨基-6-O-(2-乙酰氨基-2-脱氧-β-D-吡喃葡萄糖基)-2,3-二脱氧-α-D-吡喃葡萄糖苷-3-基]-(R)-乳酰基)-L-丙氨酰-D-异谷氨酰胺甲酯(8)和-谷氨酰胺甲酯(9)。用MgO-甲醇处理6导致GlcNAc残基脱乙酰化，得到N-(2-O-[苄基2-乙酰氨基-6-O-(2-乙酰氨基-2-脱氧-β-D-吡喃葡萄糖基)-4-O-乙酰基-2,3-二脱氧-α-D-吡喃葡萄糖苷-3-基]-(R)-乳酰基)-L-丙氨酰-D-异谷氨酰胺甲酯(11)和-谷氨酰胺甲酯(12)的混合物。肽聚糖相关结构的苄基或甲酯保护与任何需要碱性介质的反应都不兼容。2与L-丙氨酰-D-异谷氨酰胺叔丁酯缩合得到N-(2-O-[苄基2-乙酰氨基-6-O-(2-乙酰氨基-3,4,6-三-O-乙酰基-2-脱氧-β-D-吡喃葡萄糖基)-2,3-二脱氧-α-D-吡喃葡萄糖苷-3-基]-(R)-乳酰基-L-丙氨酰-D-异谷氨酰胺叔丁酯(16)，在泽普伦条件下对其进行脱乙酰化反应，未发生副反应，得到N-(2-O-[苄基2-乙酰氨基-6-O-(2-乙酰氨基-2-脱氧-β-D-吡喃葡萄糖基)-2,3-二脱氧-α-D-吡喃葡萄糖苷-3-基]-(R)-乳酰基)-L-丙氨酰-D-异谷氨酰胺叔丁酯(17)。