99(P-32) 光学活性インゲノールの合成(ポスター発表の部)

概要

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Ingenol is a diterpenoid isolated from Euphorbia ingens, possessing a bicyclo[4.4.1]undecane skeleton with a highly strained inside, outside-intrabridgehead stereochemistry. Several strategies for construction of the unique skeleton have been reported, however, direct cyclization to the inside, ousidet-bicyclo[4.4.1]undecane system has not been reported. Recently, two total syntheses in a racemic form using the aforementioned strategies were reported by Winkler and Tanino-Kuwajima. We would like to report the construction of strained carbon skeletons of ingenol by direct cyclization with ring-closing olefin metathesis (RCM). With well-designed diene compounds 4, 23, and 24, RCM was found to be applicable to the formation of a highly strained skeleton of ingenol, and formal total synthesis of optically active ingenol (1) was achieved. The key features of this synthesis are construction of an A-ring by spirocyclization of ketone 21 with an allylic chloride unit and ring closure of a B-ring by olefin metathesis. Starting from Funk's keto ester 17, the key intermediate aldehyde 27 in Winkler's total synthesis was synthesized in eight steps in 12.5% overall yield. This strategy of direct cyclization of a strained inside-outside skeleton provided the first easy access to optically active ingenol.
天然有機化合物討論会の論文
2004-10-01