Improved synthesis of rupintrivir

DaiZong Lin; WangKe Qian; Rolf Hilgenfeld; HuaLiang Jiang; KaiXian Chen; Hong Liu

doi:10.1007/s11426-011-4478-5

Improved synthesis of rupintrivir

Sci China Chem. 2012;55(6):1101-1107. doi: 10.1007/s11426-011-4478-5. Epub 2012 Jan 4.

Authors

DaiZong Lin¹, WangKe Qian², Rolf Hilgenfeld^{1

3}, HuaLiang Jiang¹, KaiXian Chen¹, Hong Liu¹

Affiliations

¹ 1State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 201203 China.
² 2School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, 110016 China.
³ 3Institute of Biochemistry, Center for Structural and Cell Biology in Medicine, University of Luebeck, 23538 Luebeck, Germany.

Abstract

An improved synthesis of rupintrivir (AG7088) was accomplished using three amino acids (l-glutamic acid, d-4-fluorophenylalanine, and l-valine) as the building blocks. The key fragment ketomethylene dipeptide isostere was constructed with the valine derivative and phenylpropionic acid derivative, followed by coupling with a lactam derivative and an isoxazole acid chloride to provide AG7088 totally in eight steps.

Keywords: AG7088; rupintrivir; synthesis.