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

• Published in: Organic letters Vol. 11; no. 5; pp. 1099 - 1102
• Main Authors: Smith, Amos B, Dong, Shuzhi
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 05-03-2009
• Subjects: Aminoglycosides - chemical synthesis; Aminoglycosides - chemistry; Catalysis; Molecular Structure; Myxococcales - chemistry; Polyenes - chemical synthesis; Polyenes - chemistry; Stereoisomerism
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/ol802942j

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.