Total synthesis of cystothiazoles A and C.
Total synthesis of cystothiazoles A and C.
复制标题
囊噻唑A和C的全合成。
DOI：
10.1021/jo0106905
复制
发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Clark,MP
中科院分区：
文献类型：
--
作者：
Williams,DR;Patnaik,S;Clark,MP
本文描述了一条以对映体控制制备胱噻唑A和C的有效途径。这些半胱噻唑具有很强的抗真菌活性，并在细胞色素bc1复合体的特定位置作为线粒体氧化的新型抑制剂发挥作用。这些研究勾勒出一个通用和灵活的计划，可以很容易地适应于各种相关的五元杂环系统的合成和结构−活性关系的生物学研究。核心的[2，4‘]双噻唑成分8分六步合成，并使用Horner−Emmons烯化反应生成α，β-不饱和酯10，为不对称Evans Aldol过程奠定了基础，该过程建立了所需的C4/C5立体化学。最后，通过对前体β-酮酯22a和22b进行立体控制的O-烷基化反应，合成了胱噻唑类化合物A和C。
An efficient pathway culminating in the enantiocontrolled preparation of cystothiazoles A and C has been described. The cystothiazoles demonstrate potent antifungal activity and function as novel inhibitors of mitochondrial oxidation at a specific site on the cytochrome bc1complex. These studies outline a general and flexible plan that can be readily adapted for the synthesis of a variety of related five-membered heterocyclic systems and for biological investigations of structure−activity relationships. The core [2,4‘]bisthiazole component8was prepared in six steps, and the use of the Horner−Emmons olefination to yield theα,β-unsaturated ester10set the stage for an asymmetric Evans aldol process, which established the required C4/C5stereochemistry. Finally the cystothiazoles A and C were prepared via a stereocontrolled O-alkylation of the precursorβ-keto esters22aand22b.