Efficient synthesis of (R)-ochratoxin alpha, the key precursor to the mycotoxin ochratoxin A

Abstract

Two new routes for the synthesis of enantiomerically pure ochratoxin alpha ((3R)-OTα) are presented, which is the key intermediate for the synthesis of ochratoxin A (OTA) by coupling reaction with the amino acid l-phenylalanine. The key step of both routes is the one pot directed ortho-metalation/alkylation/lactonization of unprotected and suitably functionalized aromatic carboxylic acids, using lithium tetramethylpiperidide (LTMP) and (R)-propylene oxide.