Garware Research Centre, Department of Chemistry, University of Pune, Pune 411007, India.
Bioorg Med Chem. 2010 Nov 15;18(22):7799-803. doi: 10.1016/j.bmc.2010.09.055. Epub 2010 Oct 21.
The first stereoselective synthesis of (2S,3R,6S)-6-methyl-3-hydroxy-piperidine-2-carboxylic acid (-)-6 and (2R,3R,6S)-6-methyl-(2-hydroxymethyl)-piperidine-3-ol (+)-7 was achieved starting from readily available d-glucose in 14 steps with 17% overall yield for both the compounds. The key feature of the present strategy includes the Wittig-olefination for the preparation of required conjugated keto-azide 9 and construction of 2,3,6-trisubstituted piperidine skeleton 11 by applying intramolecular reductive cyclization of conjugated keto-azide intermediate. The glycosidase inhibitory activity of compounds 6 and 7 towards several glycosidases has been evaluated.
（2S，3R，6S）-6-甲基-3-羟基-2-哌啶羧酸（-）-6 和（2R，3R，6S）-6-甲基-（2-羟甲基）-3-哌啶醇（+）-7 的首次立体选择性合成是从易得的 d-葡萄糖出发，经过 14 步反应，以 17%的总收率得到这两个化合物。本策略的关键特点包括 Wittig-烯烃化反应，用于制备所需的共轭酮基叠氮化物 9，以及通过应用共轭酮基叠氮化物中间体的分子内还原环化反应，构建 2,3,6-三取代哌啶骨架 11。已评估了化合物 6 和 7 对几种糖苷酶的糖苷酶抑制活性。
