β-Amino ester route to tussilagine, isotussilagine and (–)-petasinecine

Abstract

Condensation of enantiopure β-amino ester 2a with methyl pyruvate provides two diastereoisomers 3 and 4. Both 3 and 4 are subjected to hydrogenation followed by cyclization producing pyrrolidinones 5 and 8. From 5 and 8 isotussilagine and tussilagine are obtained respectively, by using a Mitsunobu reaction as a key step. In a similar manner, (–)-petasinecine is synthesized from the condensation product of 2b with ethyl glyoxalate.