Total Synthesis of Apoptolidin: Completion of the Synthesis and Analogue Synthesis and Evaluation
- 21 November 2003
- journal article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 125 (50), 15443-15454
- https://doi.org/10.1021/ja030496v
Abstract
The total synthesis of apoptolidin (1) is reported together with the design, synthesis, and biological evaluation of a number of analogues. The assembly of key fragments 6 and 7 to vinyl iodide 3 via dithiane coupling technology was supplemented by a second generation route to this advanced intermediate involving a Horner−Wadsworth−Emmons coupling of fragments 22 and 25. The final stages of the synthesis featured a Stille coupling between vinyl iodide 3 and vinylstannane 2, a Yamaguchi lactonization, a number of glycosidations, and final deprotection. The developed synthetic technology was applied to the construction of several analogues including 74, 75, and 77 which exhibit significant bioactivity against tumor cells.Keywords
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