Total synthesis of 2‴,5‴-diepisilvestrol and its C1''' epimer: Key structure activity relationships at C1''' and C2'''

Abstract

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 C''' has a large effect on the biological activity. © 2012 The Ameri..