Total Synthesis of (+)-α-Onocerin in Four Steps via Four-Component Coupling and Tetracyclization Steps

• Published in: Journal of the American Chemical Society Vol. 124; no. 38; pp. 11290 - 11291
• Main Authors: Mi, Yuan, Schreiber, Jürg V, Corey, E. J
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 25-09-2002
• Subjects: Alicyclic compounds, terpenoids, prostaglandins, steroids; Chemistry; Cyclization; Exact sciences and technology; Organic chemistry; Preparations and properties; Stereoisomerism; Terpenoids; Triterpenes - chemical synthesis; Terpenoid; Cyclization; Enantioselectivity; Bicyclic compound; Naphthalene derivatives; Total synthesis; Chemical coupling
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja027373f

A remarkably short (four steps, 31% overall yield) enantioselective synthesis of the structurally unique C 2-symmetric tetracyclic triterpene (+)-α-onocerin (1) has been developed. The brevity of this mechanism depends on the assembly of four fragments (two molecules of a chiral epoxy ketone and two molecules of vinyllithium) to generate the chiral bis-epoxide 4 in one step, and on the efficient formation of all four carbocyclic rings in one step by cation−olefin tetracyclization. New and general methodology for the conversion of vinyl tert-butyldimethylsilyl ethers to vinyl triflates with retention of E or Z olefinic geometry also was utilized in the synthesis of 1. A short enantioselective synthesis of a non-C 2-symmetric diastereomer of 1 is also described which uses the new methodology.