Asymmetric total syntheses of two 3-acyl-5,6-dihydro-2H-pyrones: (R)-podoblastin-S and (R)-lachnelluloic acid with verification of the absolute configuration of (-)-lachnelluloic acid

Abstract

Expedient asymmetric total syntheses of both (R)-podoblastin-S and (R)-lachnelluloic acid, representative of natural 3-acyl-5,6-dihydro-2H-pyran-2-ones, were performed. Compared with the reported total synthesis of (R)-podoblastin-S (14 steps, overall 5% yield), the present study was achieved in only five steps in an overall 40% yield and with 98% ee (HPLC analysis). In a similar strategy, the first asymmetric total synthesis of the relevant (R)-lachnelluloic acid was achieved in an overall 40% yield with 98% ee (HPLC analysis). The crucial step utilized readily accessible and reliable Soriente and Scettri's Ti(OiPr)4/(S)-BINOL-catalyzed asymmetric Mukaiyama aldol addition of 1,3-bis(trimethylsiloxy)diene, derived from ethyl acetoacetate with n-butanal for (R)-podoblastin-S and n-pentanal for (R)-lachnelluloic acid. With the comparison of the specific rotation values between the natural product and the synthetic specimen, the hitherto unknown absolute configuration at the C(6) position of (-)-lachnelluloic acid was unambiguously elucidated as 6R.