Semisynthesis of Ingenol 3-Angelate (PEP005): Efficient Stereoconservative Angeloylation of Alcohols

Abstract

A high-yielding method was developed for the preparation of ingenol 3-angelate (PEP005, ingenol mebutate) via the corresponding 5,20-acetonide without concomitant isomerization of the angelate (<i>Z</i>-form) to the corresponding tiglate (<i>E</i>-form). The general scope of the stereoconservative esterification method was further evaluated on several different alcohols, giving the angelates in up to quantitative yield without isomerization to the tiglate.