Total Synthesis and Absolute Stereochemical Assignment of Microgrewiapine A and Its Stereoisomers.

Abstract

Total synthesis of both enantiomers of (-)-(2 S,3 R,6 S)- and (+)-(2 R,3 S,6 R)-microgrewiapine A along with (+)-microcosamine A and (-)-6- epi-microgrewiapine A from chiral 1-(α-methylbenzyl)-aziridine-2-carboxylate was accomplished for the first time. Key steps involved in this synthesis include one-pot reductive ring-opening of aziridine, debenzylation, intramolecular N-alkylation to obtain the key piperidine ring, and Julia-Kociensky olefination. The absolute configuration of natural microgrewiapine A is assigned as (+)-(2 R,3 S,6 R), which is opposite to the originally proposed structure by comparing optical rotation data of both synthetic enantiomers.