Total syntheses of (±)-crinane, (±)-crinamine and (±)-6a-epi-crinamine via the regioselective Stille coupling and Diels-Alder reaction of 3,5-dibromo-2-pyrone

Abstract

Belonging to the Amarylidaceae natural product family, the crinane-type alkaloids 1 - 3 elicit continuing interest in the synthetic community due in part to their intriguing physiological activities as exemplified by the recent study unveiling the highly selective apoptosis induction properties of crinamine 2 and haemanthamine 3 against tumor cells at as low as micromolar concentration. We have devised a new synthetic route to (±)-crinine, crinamine as well as 6a-epi-crinamine from 3,5-dibromo-2-pyrone, via the regioselective synthesis and Diels-Alder cycloaddition of 3-(3,4-methylenedioxy-phenyl)-5-bromo-2-pyrone with TBS vinyl ether. Noted is that the vinyl bromide can be used as a handle for further derivatization.