Complementary isonitrile-based multicomponent reactions for the synthesis of diversified cytotoxic hemiasterlin analogues. Issue 48 (15th October 2015) - Lesma, Giordano
Abstract : A multicomponent strategy proved to be suitable for the concise and convergent generation of hemiasterlin derivatives, also including non-peptidic analogues. Abstract : A small family of structural analogues of the antimitotic tripeptides, hemiasterlins, have been designed and synthesized as potential inhibitors of tubulin polymerization. The effectiveness of a multicomponent approach was fully demonstrated by applying complementary versions of the isocyanide-based Ugi reaction. Compounds strictly related to the lead natural products, as well as more extensively modified analogues, have been synthesized in a concise and convergent manner. In some cases, biological evaluation provided evidence for strong cytotoxic activity (six human tumor cell lines) and for potent inhibition of tubulin polymerization.