Enantioselective total synthesis of either enantiomer of the antifungal antibiotic preussin (L-657,398) from (S)-phenylalanine

Article abstract of DOI:10.1021/ja00104a005

Enantioselective total syntheses of the antifungal agent (+)-preussin (1) and its enantiomer (-)-1 from (S)-phenylalanine are described. The central transformations are protic acid-promoted aza-Cope rearrangement - Mannich cyclization reactions (12 → 19 and 13 → 27). Retro-Mannich fragmentation-Mannich cyclization (27 → 28) is key to the formation of (-)-1. This study demonstrates, for the first time, that enantioenriched substituted pyrrolidines can be prepared using the aza-Cope-Mannich rearrangement.