American Chemical Society
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Total Synthesis of 2‴,5‴-Diepisilvestrol and Its C1‴ Epimer: Key Structure Activity Relationships at C1‴ and C2‴

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journal contribution
posted on 2016-02-20, 13:37 authored by Jennifer M. Chambers, David C. S. Huang, Lisa M. Lindqvist, G. Paul Savage, Jonathan M. White, Mark A. Rizzacasa
The first total synthesis of the low-abundance natural product 2‴,5‴-diepisilvestrol (4) is described. The key step involved a Mitsunobu coupling between cyclopenta­[b]­benzofuran phenol 7 and dioxane lactol 6. Deprotection then gave a 1:2.6 ratio of natural product 2‴,5‴-diepisilvestrol (4) and its C1 epimer 1‴,2‴,5‴-triepisilvestrol (15) in 50% overall yield. An in vitro protein translation inhibition assay showed that 2‴,5‴-diepisilvestrol (4) was considerably less active than episilvestrol (2), while the unnatural isomer 1‴,2‴,5‴-triepisilvestrol (15) was essentially inactive, showing that the configuration at C1‴ and C2‴ has a large effect on the biological activity.