Semisynthetic and Biotransformation Studies of (1S,2E,4S,6R,7E,11E)-2,7,11-Cembratriene-4,6-diol

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• 作者：Khalid A. El Sayed ; Surat Laphookhieo ; Muhammad Yousaf ; Justin A. Prestridge ; Amit B. Shirode ; Vikram B. Wali ; Paul W. Sylvester
• 刊名：Journal of Natural Products
• 出版年：2008
• 出版时间：January 2008
• 年：2008
• 卷：71
• 期：1
• 页码：117 - 122
• 全文大小：265K
• 年卷期：v.71,no.1(January 2008)
• ISSN：1520-6025

文摘

Tobacco-derived (1S,2E,4S,6R,7E,11E)-2,7,11-cembratriene-4,6-diol (1) and (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol (2) were first shown to display potential antitumor-promoting activity in the mid-1980s. However, very little is currently understood regarding the structural activity relationships of tobacco cembranoids. The aim of this present study was to explore antiproliferative activity of various derivatives of (1S,2E,4S,6R,7E,11E)-2,7,11-cembratriene-4,6-diol (1) using semisynthetic and biotransformation approaches. Derivatives of 1 include esterified, oxidized, halogenated, and nitrogen- and sulfur-containing compounds (3–17). Biotransformation of 1 using Mucor ramannianus ATCC 9628 and Cunninghamella elegans ATCC 7929 afforded the known 10S,11S-epoxy analogue of 1 (4) as the main metabolite. Biotransformation of the 6-O-acetyl analogue (3) using the marine symbiotic Bacillus megaterium strain MO31 afforded (1S,2E,4S,6R,7E,11E,10R)-2,7,11-cembratriene-4,6,10-triol (18). (1S,2E,4S,6R,7E,11E,13R)-2,7,11-Cembratriene-4,6,13-triol-6-O-acetate (6), (1S,2E,4S,6R,7E,11E,13S)-2,7,11-cembratriene-4,6,13-triol-6-O-acetate (7), the rearranged α-ketol (1S,2E,4S,7Z,11E)-2,7,11-cembratrien-4-ol-6-one (11), and the secocembranoid 12 showed antiproliferative activity against highly malignant +SA mammary epithelial cells with an IC₅₀ range of 15–30 µM.