抗肿瘤药。550. 由(+)-水仙环素合成10b(s)-表潘克拉他汀

Antineoplastic agents. 550. Synthesis of 10b(s)-epipancratistatin from (+)-narciclasine.

作者信息

Pettit George R, Melody Noeleen, Herald Delbert L, Knight John C, Chapuis Jean-Charles

机构信息

Cancer Research Institute and Department of Chemistry and Biochemistry, Arizona State University, P.O. Box 872404, Tempe, AZ 85287-2404, USA.

出版信息

J Nat Prod. 2007 Mar;70(3):417-22. doi: 10.1021/np068046e. Epub 2007 Mar 9.

DOI:10.1021/np068046e

PMID:17346078

Abstract

By means of a five-step reaction sequence, narciclasine (2a), isolated from Narcissus sp., was converted to 10b(S)-epipancratistatin (3a) in 5.7% overall yield. The key step entailed a radical-initiated 10b,1 C-O cleavage employing tributyltin hydride to yield a B/C cis ring juncture (3b). Biological evaluation of 10b(S)-epipancratistatin (3a) provided evidence that antineoplastic activity was reduced by a factor of 10 when the B/C trans juncture was replaced with a B/C cis ring juncture.

摘要

通过五步反应序列，从水仙属植物中分离得到的水仙环素（2a）被转化为10b(S)-表水仙环素（3a），总产率为5.7%。关键步骤是使用三丁基氢化锡引发自由基引发的10b,1 C-O裂解，以产生B/C顺式环连接（3b）。对10b(S)-表水仙环素（3a）的生物学评价提供了证据，表明当B/C反式连接被B/C顺式环连接取代时，抗肿瘤活性降低了10倍。