Department of Chemistry, Université de Montréal, Canada H3C 3J7.
J Org Chem. 2010 Aug 20;75(16):5601-18. doi: 10.1021/jo100956v.
An enantioselective synthesis of the antifungal natural product (+)-ambruticin S has been accomplished starting with the readily available methyl alpha-d-glucopyranoside, (R)-Roche ester, and (S)-glycidol as chirons, which encompassed seven of the 10 stereogenic centers of the target molecule. The remaining three centers were set by a highly diastereoselective, asymmetric cyclopropanation employing a chiral, nonracemic phosphonamide reagent. Our strategy for the construction of the dihydropyran subunit involved a highly syn-selective Lewis acid catalyzed 6-endo-trig cyclization. Other key steps in the synthesis featured an epoxide opening with a dithiane anion, two efficient phosphonamide-anion based olefinations, and a late-stage C-glycosylation.
一种对映选择性合成抗真菌天然产物 (+)-ambruticin S 的方法已经完成，起始原料为易得的甲基 α-D-吡喃葡萄糖苷、(R)-Roche 酯和 (S)-缩水甘油，它们包含目标分子的 10 个立体中心中的 7 个。其余的三个中心是通过高度非对映选择性、不对称环丙烷化反应采用手性非外消旋膦酰胺试剂来设置的。我们构建二氢吡喃亚基的策略涉及高度 syn-选择性路易斯酸催化的 6-endo-trig 环化。合成中的其他关键步骤包括使用二硫杂环戊烷阴离子开环、两个有效的膦酰胺阴离子基烯烃化以及晚期 C-糖苷化。
