1099-0690/asset/2046_left.gif?v=1&s=0ec9ed8843eb5403f667ad940f5a1c68cb5ef011)
1099-0690/asset/2046_right.gif?v=1&s=b2caf576ff74b55a6a4748bd86a910901b664c52)
Full Paper
First Total Synthesis of the Potent Anticancer Natural Product Dideoxypetrosynol A: Preparation of the “Skipped” (Z)-Enediyne Moiety by Oxidative Coupling of Homopropargylphosphonium Ylide
Article first published online: 21 AUG 2008
DOI: 10.1002/ejoc.200800593
Copyright © 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1099-0690/asset/cover.gif?v=1&s=2cc52719b72cfaff52154639cf010f601d160064 "European Journal of Organic Chemistry")
Additional Information
How to Cite
Gung, B. W. and Omollo, A. O. (2008), First Total Synthesis of the Potent Anticancer Natural Product Dideoxypetrosynol A: Preparation of the “Skipped” (Z)-Enediyne Moiety by Oxidative Coupling of Homopropargylphosphonium Ylide. European Journal of Organic Chemistry, 2008: 4790–4795. doi: 10.1002/ejoc.200800593
Publication History
- Issue published online: 16 SEP 2008
- Article first published online: 21 AUG 2008
- Manuscript Received: 19 JUN 2008
Funded by
- National Institutes of Health (NIH). Grant Number: GM069441
Keywords:
- Total synthesis;
- Antitumor agents;
- Natural products;
- (Z)-Enediyne;
- Dideoxypetrosynol A
Graphical Abstract
Dideoxypetrosynol A (1) was found to have potent anticancer activity and exhibited an ED50 of 0.02 μg/mL against human ovarian cancer cells and of 0.01 μg/mL against human skin cancer cells. Dideoxypetrosynol A (1) was also found to inhibit DNA replication at the initiation stage. The first total synthesis of dideoxypetrosynol A is reported.
Abstract
Dideoxypetrosynol A is a C30 polyacetylenic alcohol with C2 symmetry. The first total synthesis of both enantiomers of the potent anti-cancer natural product (+)- and (–)-dideoxypetrosynol A is reported. The key step is an oxidative coupling of a homopropargylphosphonium ylide to prepare the “skipped” (Z)-enediyne moiety. The natural dideoxypetrosynol A was isolated as a racemic mixture as shown in structure 1. The absolute configurations of the chiral centers are established for the (+)- and (–)-enantiomers using Burgess' enzymatic resolution procedure with Pseudomonas AK lipase. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)