Total synthesis of kendomycin: a macro-C-glycosidation approach.
Total synthesis of kendomycin: a macro-C-glycosidation approach.
复制标题
DOI：
10.1021/ja0447154
复制
发表时间：
2004-10
影响因子：
15
通讯作者：
Yu Yuan;H. Men;Chulbom Lee
中科院分区：
文献类型：
--
作者：
Yu Yuan;H. Men;Chulbom Lee
肯德霉素，也称为（-）-TAN 2162，是从链霉菌属分离的一种新型聚酮衍生安莎霉素，其分别对内皮素和降钙素受体表现出有效的拮抗剂和激动剂活性。这种细菌代谢物还具有针对一系列革兰氏阳性和阴性细菌的强抗生素活性，以及对人类癌细胞系生长的细胞抑制作用。以一种新的大糖苷化反应为关键步骤，首次实现了对映选择性全合成肯多霉素。含有四氢吡喃和苯并呋喃部分的无环前体的Friedel-Crafts型闭环以良好的产率产生作为单一立体异构体的大环，从而建立柄核的芳基C-糖苷键。该反应需要酚糖基受体，并且似乎通过快速O-糖苷化随后缓慢重排为芳基C-糖苷来进行。所需的开环大环通过两个亚基的Pd（0）催化的B-烷基Suzuki-Miyaura交叉偶联制备，所述亚基进而可以以模块化方式从容易获得的结构单元快速组装。
Kendomycin, also known as (-)-TAN 2162, is a novel polyketide-derived ansamycin isolated from Streptomyces sp., which exhibits potent antagonist and agonist activities at the endothelin and calcitonin receptors, respectively. This bacterial metabolite also possesses a strong antibiotic activity against a range of gram-positive and -negative bacteria and cytostatic effects on the growth of human cancer cell lines. When a novel macroglycosidation reaction is employed as the key step, the first enantioselective total synthesis of kendomycin has been accomplished. A Friedel-Crafts-type ring closure of the acyclic precursor containing tetrahydropyran and benzofuran moieties produces the macrocycle as a single stereoisomer in good yield, thus establishing the aryl C-glycosidic linkage of the ansa core. This reaction requires a phenolic glycosyl acceptor and appears to proceed through a rapid O-glycosidation followed by a slow rearrangement to an aryl C-glycoside. The requisite secomacrocycle is prepared by the Pd(0)-catalyzed B-alkyl Suzuki-Miyaura cross-coupling of two subunits, which in turn can be expeditiously assembled from readily available building blocks in a modular fashion.