Concise Total Synthesis of the Bisnorditerpene (+)-rel-(5b,8a,10a)-8-hydroxy-13-methylpodocarpa-9(11),13-diene-3,12-dione

Abstract： The bisnorditerpene rel-(5b,8a,10a)-8-hydroxy-13-methylpodocarpa-9(11),13-diene-3,12-dione (1) was isolated from Croton regelianus var. matosii, popularly known as 'velame de cheiro', which is used as traditional medicine in 'Caatinga', Northeast region of Brazil, in 2010 by Pessoa et al. Bisnorditerpene 1 has larvicidal, nematicidal, in vitro and in vivo antitumor properties. It has a 6-6-6 ring pattern, three chiral carbons, and two partial structures, including a 1,4-quinoid moiety with a chiral hydroxy and a decalin-type system containing a carbonyl group and three angular methyl groups. The first asymmetric concise total synthesis of the bisnorditerpene(+) (1) has been accomplished in 7 steps with 18.5% yield. The key steps of the synthesis include a cationic domino cyclization to construct the core skeleton and an oxidative dearomatization to form the 1,4-quinoid moiety of this natural product.