An 11-Step Synthesis of (+)-Neopeltolide by the Macrocyclization/Transannular Pyran Cyclization Strategy

Abstract

Total synthesis of (+)-neopeltolide, a potent antiproliferative marine macrolide natural product, was accomplished in 11 steps from a commercially available inexpensive material. The 14-membered macrolactone skeleton embedded with a 2,6-cis-substituted tetrahydropyran ring was synthesized in an expedient fashion by our newly developed macrocyclization/transannular pyran cyclization strategy. A concise synthetic entry to the oxazole-containing side chain was developed by exploiting palladium-catalyzed cross-coupling reactions. Total synthesis of (+)-9-epi-neopeltolide was also achieved in 12 steps by late-stage stereochemical diversification at the C9 position.