Synthesis, Conformation, and Biological Activity of Teleocidin Mimics, Benzolactams. A Clarification of the Conformational Flexibility Problem in Structure-Activity Studies of Teleocidins

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• 作者：Yasuyuki Endo ; Michihiro Ohno ; Masaaki Hirano ; Akiko Itai ; and Koichi Shudo
• 刊名：Journal of the American Chemical Society
• 出版年：1996
• 出版时间：February 28, 1996
• 年：1996
• 卷：118
• 期：8
• 页码：1841 - 1855
• 全文大小：630K
• 年卷期：v.118,no.8(February 28, 1996)
• ISSN：1520-5126

文摘

Tumor-promoter teleocidins and their active congeners(indolactams) are known to exist in an equilibriumbetween at least two conformational states in solution, the twist andsofa form, due to cis-trans isomerization oftheamide bond and the steric effects of substituents on the nine-memberedlactam ring. Benzolactam-Vs, in which theindole ring of indolactams is replaced with a benzene ring, weredesigned and synthesized in an attempt to reproducethe active conformation of teleocidins. Among these benzolactams,eight-membered lactams (benzolactam-V8) canonly exist in the twist form, and 9- and 10-membered lactams(benzolactam-V9 and -V10) exist exclusively in thesofa form in solution. The stronger biological activity ofbenzolactam-V-8-310 than that of indolactam-V (IL-V)and the inactivity of benzolactam-V-9-310 for differentiation inducingactivity of HL-60 clearly indicated that thetwist form is close to the active conformation ofteleocidins.