Department of Chemistry, Texas A&M University, P.O. Box 30012, College Station, Texas 77842-3012, United States.
Org Lett. 2012 Mar 16;14(6):1394-7. doi: 10.1021/ol300105q. Epub 2012 Feb 24.
Cyclopropanations of alkene-containing natural products that proceed under mild conditions are reported for simultaneous arming and structure-activity relationship studies. An alkynyl diazo ester under Rh(II) catalysis is employed for cyclopropanations of electron-rich olefins while an alkynyl sulfonium ylide is used for electron-poor olefins. This approach enables simultaneous natural product derivatization for SAR studies and arming (i.e., via alkyne attachment) for subsequent conjugation with reporter tags (e.g., biotin, fluorophores, photoaffinity labels) for mechanism of action studies including cellular target identification and proteome profiling experiments.
报道了在温和条件下进行的含烯烃天然产物的环丙烷化反应,用于同时进行的武器化和构效关系研究。在 Rh(II)催化下,使用炔基重氮酯进行富电子烯烃的环丙烷化反应,而使用炔基硫叶立德进行缺电子烯烃的环丙烷化反应。这种方法能够同时对天然产物进行衍生化以进行 SAR 研究,并进行武器化(即通过炔键连接),以便随后与报告标签(如生物素、荧光团、光亲和标记物)缀合,用于作用机制研究,包括细胞靶标鉴定和蛋白质组分析实验。