Enantioselective total syntheses and determination of absolute configuration of marine toxins, oxazinins

Abstract

The enantioselective total syntheses of natural marine toxins, oxazinin-1, -2, -4, -5, -6 and linear precursor preoxazinin-7 are described. The synthetic highlights include Sharpless asymmetric aminohydroxylation and dihydroxylation, oxa-Michael reaction and intramolecular diastereoselective addition of an appropriate hydroxyl substituent to a 3-methyleneindolenine for the construction of the morpholine ring as key steps. The synthetic route also allowed the synthesis of the epi-preoxazinin and a structurally related secondary metabolite bursatellin isolated in 1980 from sea hare Bursatella leachii pleii and its epimer.