A Convergent Approach for Protected (+)-Paecilomycin F

Abstract

Background: A stereoselective synthetic strategy towards (+)-paecilomycin F is reported. The approach utilizes readily available commercial 2,4,6-trihydroxybenzoic acid and easily accessible chiral R(+)-propylene oxide as starting materials. Methods: The synthesis involves regioselective Grignard reaction, Wittig reaction, Sharpless asymmetric dihydroxylation, Barbier-type allylation, Stille coupling and ring closing metathesis as key reactions. Results: The target molecule is produced in a 7-step linear sequence with an overall yield of 20% starting from 2,4,6-trihydroxy benzoic acid or 12-step sequence with an overall yield of 12.95% starting from R(+)-propylene oxide. Conclusion: The aromatic fragment synthesis was achieved using earlier known protocols starting from 2,4,6-trihydroxybenzoic acid (vide infra).