An Efficient, Second-Generation Synthesis of the Signature Dioxabicyclo[3.2.1]octane Core of (+)-Sorangicin A and Elaboration of the (Z,Z,E)-Triene Acid System

An efficient, second-generation synthesis of the signature dioxabicyclo[3.2.1]octane core of (+)-sorangicin A (1), In conjunction with an effective, stereocontrolled protocol to arrive at the requisite (Z,Z,E)-triene acid system has been developed. Highlights of the core construction entail a three-component union, a KHMDS-promoted epoxide ring formation-ring opening cascade, a Takai olefination, and a chemoselective Sharpless dihydroxylation. Assembly of the triene acid system was then achieved via Stille cross-coupling with the ethyl ester of (Z,Z)-5-tributylstannyl-2,4-pentadienoic acid, followed by mild hydrolysis preserving the triene configuration.