Paquette Leo A, Peng Xiaowen, Yang Jiong, Kang Ho-Jung
Evans Chemical Laboratories, The Ohio State University, Columbus, OH 43210-1185, USA.
J Org Chem. 2008 Jun 20;73(12):4548-58. doi: 10.1021/jo8004233. Epub 2008 May 20.
An enantiodivergent strategy for the total chemical synthesis of both naturally occurring (+)-fomannosin (1) and its (-)-antipode (ent-1) from alpha-D-glucose has been developed and successfully implemented. The key steps in the overall pathway include the following: (i) application of the zirconocene-mediated ring contraction of vinyl furanosides for the construction of highly substituted cyclobutanols; (ii) the use of ring-closing metathesis to form the pendant five-membered ring; (iii) making recourse to a monothio malonic ester to allow for chemoselective reduction to sensitive lactone intermediate 45; (iv) hydroxyl-directed dihydroxylation with OsO(4) to generate 48; and (v) sequential elimination via a cyclic sulfite and a cyclobutyl triflate. The bridge between the enantiomeric series consisted of a six-step linkup involving the structural modification of 22 so as to generate ent-30b. Optical activity was fully preserved throughout.
已开发并成功实施了一种从α-D-葡萄糖全化学合成天然存在的(+)-福曼诺辛(1)及其(-)-对映体(ent-1)的对映发散策略。整个途径中的关键步骤如下：(i)应用锆茂介导的乙烯基呋喃糖苷的环收缩来构建高度取代的环丁醇；(ii)使用闭环复分解反应形成侧链五元环；(iii)借助单硫代丙二酸酯实现对敏感内酯中间体45的化学选择性还原；(iv)用OsO(4)进行羟基导向的二羟基化反应生成48；以及(v)通过环状亚硫酸盐和环丁基三氟甲磺酸酯进行顺序消除反应。对映体系列之间的桥梁由一个六步连接组成，涉及对22进行结构修饰以生成ent-30b。整个过程中光学活性得以完全保留。
