Rocaglamide derivatives (flavaglines) from the genus Aglaia which possess highly substituted cyclopenta<b>benzofuran core ring systems have garnered significant synthetic attention due to their complex structures and potent biological activities.  Silvestrol, a novel flavagline with a unique dioxanyloxy side chain, has demonstrated potent cytotoxic activity (low nM IC50 values) in vitro against numerous human cancer cell lines. Importantly, silvestrol has displayed this potent cytotoxicity against acute and chronic lymphoblastic leukemia while exhibiting selectivity. Our goal has been to develop a versatile and modular synthesis of silvestrol that would permit deep-seated structural changes to the natural product, functional group manipulation, and structural simplification. This ongoing effort has facilitated the synthesis of analogues designed to explore the structure-activity relationship, delineate the mechanism of action, and ultimately improve the pharmacological profile of silvestrol.

Flexible synthetic approach to the synthesis of the rocaglamide derivative silvestrol

244th National Meeting (2012)

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