Natural Products Chemistry Division, Indian Institute of Chemical Technology , Hyderabad 500007, India.
J Org Chem. 2016 May 20;81(10):4252-61. doi: 10.1021/acs.joc.6b00616. Epub 2016 Apr 28.
The formal total synthesis of both the enantiomers of cyclophellitol and conduritol-B and synthesis of conduramine-B derivative have been achieved from a common intermediate, obtained by regio- and stereoselective vicinal functionalization of a diene utilizing an intramolecular sulfinyl group as a nucleophile, followed by stereoselective preparation of an allylic sulfide by reaction of vinylzinc bromide with an electrophilic α-chloro sulfide, and last by ring-closing metathesis reaction as the key steps. The sulfoxide, sulfilimine, and sulfur ylid prepared from this common intermediate have been transformed into derivatives of conduritol-B, conduramine-B, and (-)-cyclophellitol, respectively. The silyl sulfide was converted via sila-Pummerer rearrangement, hydrolysis, and reduction in an one-pot operation to a hydroxymethyl group. [2,3]-Wittig-Still rearrangement was employed for the synthesis of (+)-cyclophellitol. The potential utility of sulfur intermediates as nucleophilic and electrophilic partners in total synthesis is elegantly demonstrated.
已通过区域和立体选择性的双烯官能化反应，利用分子内亚磺酰基作为亲核试剂，从一个共同的中间体中实现了环磷醇和康杜醇-B 的对映异构体的全合成，以及康杜胺-B 衍生物的合成。随后，通过乙烯基溴化锌与亲电性的α-氯代亚砜的反应，立体选择性地制备了烯丙基硫化物，最后通过闭环复分解反应作为关键步骤。从这个共同的中间体制备的亚砜、亚磺酰亚胺和硫叶立德已分别转化为康杜醇-B、康杜胺-B 和（-）-环磷醇的衍生物。硅基硫化物通过硅-普梅尔（sila-Pummerer）重排、水解和在一锅操作中的还原转化为羟甲基。[2,3]-Wittig-Still 重排用于（+）-环磷醇的合成。硫中间体作为亲核试剂和亲电试剂在全合成中的应用得到了很好的证明。
