Asymmetric synthesis of N,O-diacetyl-3-epi-xestoaminol C: structure and absolute configuration confirmation of 3-epi-xestoaminol C

Abstract

The asymmetric synthesis of N,O-diacetyl-3-epi-xestoaminol C is reported. The synthesis employs diastereoselective aminohydroxylation of tert-butyl crotonate [conjugate addition of lithium (S)-N-benzyl-N-(α-methylbenzyl)amide, then in situ enolate oxidation with (+)-camphorsulfonyloxaziridine (CSO)] and a diastereoselective reduction protocol as the key stereodefining steps. The synthetic sample of the natural product was isolated as its N,O-diacetyl derivative for ease of purification; this material was prepared in ten steps and 17% overall yield from commercially available tert-butyl crotonate. This synthesis confirms unambiguously both the assigned structure and absolute (S,S)-configuration of the natural product.