Bian Jianwei, Van Wingerden Matthew, Ready Joseph M
Department of Biochemistry, The University of Texas Southwestern Medical Center at Dallas, Texas 75390-9038, USA.
J Am Chem Soc. 2006 Jun 14;128(23):7428-9. doi: 10.1021/ja061559n.
The nigellamine alkaloids are dolabellane diterpenes displaying potent lipid metabolism-promoting activity. Total synthesis of (+)- and (-)-nigellamine A2 has been accomplished. Absolute stereochemistry of synthetic nigellamine A2 was established through an intramolecular asymmetric allylic alkylation using a Pd(phosphinooxazoline) catalyst. Other notable transformations include a radical alkynylation, a diastereoselective Nozaki-Hiyama-Kishi cyclization, and a regio- and stereoselective catalytic epoxidation. On the basis of X-ray crystallographic analysis of an optically active intermediate, we have confirmed the assigned absolute stereochemistry of the natural product. Minor modifications of the synthetic sequence outlined here should provide access to the other nigellamine alkaloids.
黑种草胺生物碱是具有显著促进脂质代谢活性的多拉贝拉烷二萜类化合物。（+）-和（-）-黑种草胺A2的全合成已完成。通过使用钯（膦恶唑啉）催化剂的分子内不对称烯丙基烷基化反应确定了合成黑种草胺A2的绝对立体化学结构。其他值得注意的转化反应包括自由基炔基化反应、非对映选择性的野依-日向-岸环化反应以及区域和立体选择性催化环氧化反应。基于对一种旋光性中间体的X射线晶体学分析，我们已确认了天然产物所确定的绝对立体化学结构。对本文所述合成路线进行微小修改应能实现其他黑种草胺生物碱的合成。
