Formal Synthesis of Optically Active Ingenol via Ring-Closing Olefin Metathesis

• DOI: 10.1021/jo048833l
• Publication Date: 2004-11-05T05:45:44Z
• Authors: Kazushi Watanabe; Yuto Suzuki; Kenta Aoki; Akira Sakakura; Kiyotake Suenaga; Hideo Kigoshi
• Keywords: Ring-Closing Metathesis; Diene; Salt metathesis reaction

The construction of strained carbon skeletons by ring-closing olefin metathesis (RCM) was investigated. With well-designed diene 4, RCM found to be applicable the formation a highly inside-outside bicyclo[4.4.1]undecane skeleton ingenol, bioactive diterpenoid, and formal total synthesis optically active ingenol (1) achieved. key features this are an A-ring spirocyclization ketone with allylic chloride unit, 26, ring closure B-ring metathesis. Starting from Funk's keto ester 6, intermediate aldehyde 9 in Winkler's synthesized eight steps 12.5% overall yield. This strategy direct cyclization provided first easy access ingenol.