A Formal Total Synthesis of Xanthorrhizol Based on Nucleophilic Openig of Vinyloxirane by Arylcopper Reagent

Abstract

A formal total synthesis of xanthorrhizol was achieved in short step sequence involving the nucleophilic opening of methyl 4,5-epoxy-(2E)-pentenoate (1) by arylcopper reagent.The phenolic bisabolane sesquiterpene, xanthorrhizol, was isolated from rhizomes of Curcwna xanrhorrhiza Roxb.and used as a popular remedy in gall and liver dis0rders.lIn the synthesis of this type bisabolane sesquiterpenes, the key step is the construction of desired connection bctween ammatic ring and side chain moiety.The fust synthesis of xanthorrhuol requires eleven steps begining with aromatic ketone having desired functionality.2Meanwhile, we reported the novel syntheses of several bisabolane sesquiterpenes such as curcudiol from key intermediates (A), which was obtained by our developed nucleophilic opening of methyl 4,5-epo~y-(iE)-~entenoate (1) with polymethoxytoluene in the presence of B F ~. E ~~O .~In this synthesis, the key reaction proceeded in high yield and showed the generality by arenes.However, the reaction coud not be applied to the synthesis of xanthorrhizol because it was hard to achieve the C-C bond formation at m-position of electron-releasing function such as methoxyl or hydroxyl group (Scheme 1).