Total synthesis of (−)-2-oxo epimesembranol and (+)-dihydromaritidine via a key Johnson–Claisen rearrangement

Abstract

A general approach to Sceletium alkaloids of the family Aizoaceace following a key Johnson (orthoester)–Claisen rearrangement of an enantioenriched allylic alcohol has been disclosed. The tricyclic core (1c) of cis-3a-octahydroindoline skeleton was achieved via an ester-aminolysis followed by an intramolecular aza-Michael reaction with amine under elevated temperature. Utilizing aforementioned strategy, a collective total syntheses of Sceletium alkaloids, such as (−)-2-oxo-epimesembranol (1d) [the first total synthesis], (−)-6-epimesembranol (1b), and (−)-mesembrine (1a) were shown. Further this strategy was applied for total synthesis of (+)-dihydromaritidine (2c) sharing [5,11b]-ethanophenanthridine skeleton.