Facile, efficient, and enantiospecific syntheses of 1,1′-N-linked pseudodisaccharides as a new class of glycosidase inhibitors
Facile, efficient, and enantiospecific syntheses of 1,1′-N-linked pseudodisaccharides as a new class of glycosidase inhibitors
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DOI：
10.1021/ja0470158
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发表时间：
2004-12-15
影响因子：
15
通讯作者：
Cheng, CHK
中科院分区：
文献类型：
--
作者：
Shing, TKM;Kwong, CSK;Cheng, CHK
本文报道了一种有效的海藻糖酶抑制剂1，1‘-N-连接的假二糖1，1’-N-连接的假二糖1，1‘-N-连接的假二糖1，总收率为12%。以(-)奎尼酸为原料，经15步首次合成2，2-环戊二胺，总收率为24%。合成的关键步骤是烯丙基胺和烯丙基氯之间的立体定向钯催化偶联反应。丙酮封闭基是最好的羟基保护基团，与钯催化的烯丙胺化反应相容，该反应以最少的消除二烯副产物获得了高产率的1，1‘-N-连接的假二糖。
This article describes an efficient synthesis of a potent trehalase inhibitor, 1,1'-N-linked pseudodisaccharide 1 (consisting of two valienamines), in 14 steps with an overall yield of 12% and a first synthesis of 2 (consisting of two 2-epi-valienamines) in 15 steps with an overall yield of 24% from (-)quinic acid. The synthesis involves a stereospecific palladium-catalyzed coupling reaction between an allylic amine and an allylic chloride as the crucial step. The acetonide blocking groups were shown to be the best hydroxyl protecting groups, compatible with the palladium-catalyzed allylic amination reaction that afforded high yields of the 1,1'-N-linked pseudodisaccharides with a minimum amount of an elimination diene side product.