Total Syntheses of (—)-Acutumine and (—)-Dechloroacutumine

摘要

(-)-Acutumine (1) is a tetracyclic alkaloid that was first obtained from the roots of Sinomenium acutum by Goto and Sudzuki in 1929 (Scheme 1 a). The related metabolite (—)-dechloroacutumine (2) was isolated from a chlorine-deficient culture of Menispermum dauricum in 1998. The acutumines share some structural homology to the hasubanan alkaloids (e.g., (-)-hasubanonine (3)), which are produced by plants of the genus Stephania. The stereogenic, heavily oxidized spirocyclopentenone rings of 1 and 2, dense array of heteroatom-containing functional groups, and secondary alkyl chloride functional group of 1 define these metabolites as challenging targets for synthesis. Additionally, (—)-acutu-mine (1) inhibits human T-cell proliferation and improves object and social recognition in the Wistar rat model, yet the mechanisms underlying these phenotypes have not been elucidated. Although many groups have initiated studies toward the synthesis of (—)-acutumine (1), only a single complete route has been reported, in a landmark publication by Castle and co-workers. Studies toward the synthesis of (—)-dechloroacutumine (2) have not been described, to our knowledge.