A Practical Synthesis of Renin Inhibitor MK-1597 (ACT-178882) via Catalytic Enantioselective Hydrogenation and Epimerization of Piperidine Intermediate
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- 作者：Carmela Molinaro ; Scott Shultz ; Ame虂lie Roy ; Stephen Lau ; Thao Trinh ; Re虂my Angelaud ; Paul D. O鈥橲hea ; Stefan Abele ; Mark Cameron ; Ed Corley ; Jacques-Alexis Funel ; Dietrich Steinhuebel ; Mark Weisel ; Shane Krska
- 刊名：Journal of Organic Chemistry
- 出版年：2011
- 出版时间：February 18, 2011
- 年：2011
- 卷：76
- 期：4
- 页码：1062-1071
- 全文大小：969K
- 年卷期：v.76,no.4(February 18, 2011)
- ISSN：1520-6904
文摘
A practical enantioselective synthesis of renin inhibitor MK-1597 (ACT-178882), a potential new treatment for hypertension, is described. The synthetic route provided MK-1597 in nine steps and 29% overall yield from commercially available p-cresol (7). The key features of this sequence include a catalytic asymmetric hydrogenation of a tetrasubstituted ene鈭抏ster, a highly efficient epimerization/saponification sequence of 4 which sets both stereocenters of the molecule, and a short synthesis of amine fragment 2.