ORGN 672 |
Improved synthesis of the C3-C17 domain of phorboxazole A
| Jiehao Chen, Mathias Christmann, Yingtao Lu, and Craig J. Forsyth. Department of Chemistry, University of Minnesota, 207 Pleasant St. SE, Minneapolis, MN 55455 |
Phorboxazole A and B were originally isolated from the Indian Ocean sponge Phorbas sp by Molinski and have extraordinary levels of anticancer activity. The complex structure, potent biological activity and limited availability of the natural products inspired extensive interests in the total synthesis of phorboxazoles. The first total synthesis of phorboxazole A was achieved by our research group. In the context of in-depth biological evaluation with the need of useful quantities of phorboxazoles, a rapid and flexible synthetic entry into phorboxazole A is designed. We developed an improved synthesis of the C3-C17 domain in 9 steps, which is highlighted by an iterative hetero Diels-Alder strategy for the stereocontrolled synthesis of the two methylene-linked tetrahydropyran and a retro hetero Michael/hetero Michael equilibration. The improved synthesis of C3-C17 fragment of phorboxazole A will be presented. |
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