Stereoselective total synthesis of the antiplasmodial resorcylic acid lactone paecilomycin F

Abstract

A facile and convergent approach for the total synthesis of 14-membered resorcylic acid lactone paecilomycin F is described. The synthesis emanates from the readily available inexpensive (+)-diethyl L-tartrate. Mitsunobu etherification, Stille coupling and ring-closing metathesis are key steps in the synthesis.

Total Syntheses of the Resorcylic Acid Lactones Paecilomycin F and Cochliomycin C Using an Intramolecular Loh-Type α-Allylation Reaction for Macrolide Formation

“…The conversion of macrolide 18 into the title natural products 4 and 3 was effected using the straightforward procedures shown in Scheme . Specifically, both the SEM and acetonide protecting groups associated with compound 18 could be cleaved on treatment with HCl in aqueous methanol and paecilomycin F ( 4 ) thus obtained in 91% yield. All of the NMR spectral data acquired on compound 4 matched those reported for the natural product (see Table S1 for some relevant comparisons) as did the specific rotation [[α] D 20 −103.3 ( c 0.6, methanol) vs lit .…”

“…[α] D 24 −106.4 ( c 0.28, methanol)]. The regioselective aromatic monochlorination of RAL 4 was readily effected using sulfuryl chloride in dichloromethane and cochliomycin C ( 3 ) obtained in 90% yield.…”