Synlett 2012; 23(18): 2647-2652
DOI: 10.1055/s-0032-1317415
letter
© Georg Thieme Verlag Stuttgart · New York

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

Xifu Liang*
a  Chemical Research, LEO Pharma A/S, Industriparken 55, 2750 Ballerup, Denmark
,
Gunnar Grue-Sørensen
a  Chemical Research, LEO Pharma A/S, Industriparken 55, 2750 Ballerup, Denmark
,
Anders Klarskov Petersen
b  API Development, LEO Pharma A/S, Industriparken 55, 2750 Ballerup, Denmark   Fax: +4572263320   Email: xifu.liang@leo-pharma.com
,
Thomas Högberg
a  Chemical Research, LEO Pharma A/S, Industriparken 55, 2750 Ballerup, Denmark
› Author Affiliations
Further Information

Publication History

Received: 20 August 2012

Accepted: 17 September 2012

Publication Date:
18 October 2012 (eFirst)

Dedicated to the memory of Professor Horst Prinzbach

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 (Z-form) to the corresponding tiglate (E-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.

Supporting Information

 
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