Total synthesis and biological evaluation of (-)-atrop-abyssomicin C
Total synthesis and biological evaluation of (-)-atrop-abyssomicin C
复制标题
DOI：
10.1039/c3ob40692j
复制
发表时间：
2013-09-07
影响因子：
3.2
通讯作者：
Saicic, Radomir N.
中科院分区：
文献类型：
--
作者：
Bihelovic, Filip;Karadzic, Ivanka;Saicic, Radomir N.
海洋抗生素 (-)-atrop-abyssomicin C 的对映选择性合成经过 21 个步骤完成，总产率为 1.8%（4%，基于回收的起始材料）。合成的关键步骤是通过有机催化的Tsuji-Trost反应形成官能化环己烷核心、通过金催化反应序列形成三环螺替膦酸单元以及通过Nozaki-Hiyama-Kishi反应高效十一元环闭合。生物学试验表明，所有阿比索米星衍生物对耐甲氧西林金黄色葡萄球菌菌株均具有较强的抗菌活性；然而，它们也被证明对恶性和正常体细胞都具有细胞毒性。
Enantioselective synthesis of a marine antibiotic (-)-atrop-abyssomicin C was accomplished in 21 steps, in 1.8% overall yield (4%, based on the recovered starting material). The key steps of the synthesis are the formation of the functionalized cyclohexane core by an organocatalyzed Tsuji-Trost reaction, the formation of a tricyclic spirotetronate unit by a gold-catalyzed reaction sequence and the highly efficient eleven-membered ring closure by a Nozaki-Hiyama-Kishi reaction. Biological tests showed all abyssomicin derivatives to possess strong antibacterial activity against methicillin resistant S. aureus strains; however, they also proved to be cytotoxic, both to malignant and to normal somatic cells.