Design of an aryne-platform for the synthesis of non-racemic heterocyclic allocolchicinoids

A four-step semisynthetic approach towards a highly versatile allocolchicine-related chiral aryne intermediate starting from naturally occurring colchicine was developed, and some of its synthetic transformations were studied. The in situ generated benzyne intermediate afforded a number of non-racemic heterocyclic allocolchicinoids, which were shown to exhibit potent cytotoxicity towards COLO 357, OSA and Raji cells. The proposed methodology is attractive for the synthesis of libraries of new cytotoxic tubulin inhibitors.

Automated summary

We developed a four-step semisynthetic approach to obtain a highly versatile allocolchicine-related chiral aryne intermediate from natural colchicine. The generated benzyne intermediate produced a range of non-racemic heterocyclic allocolchicinoids, which exhibited potent cytotoxicity against COLO 357, OSA, and Raji cells. This methodology is attractive for the synthesis of new libraries of cytotoxic tubulin inhibitors.