Studies on Angiotensin Converting Enzyme Inhibitors. V. The Diastereoselective Syntheis of 2-Oxomidazolidine Derivatives

• KUBOTA Hitoshi

  Reserch Laboratory of Applied Biochemistry Tanabe Seiyaku Co., Ltd.

• NUNAMI Ken-ichi

  Reserch Laboratory of Applied Biochemistry Tanabe Seiyaku Co., Ltd.

• YAMAGISHI Masafumi

  Pharmaceutical Technics Division Tanabe Seiyaku Co., Ltd.

• NISIMOTO Sigeru

  Pharmaceutical Technics Division Tanabe Seiyaku Co., Ltd

• HAYASHI Kimiaki

  Reserch Laboratory of Applied Biochemistry Tanabe Seiyaku Co., Ltd.

Abstract

A diastereoselective syntesis of imidapril (1), which is under clinical study as an antihypertensive drug based on its angiotensin converting enzyme (ACE)-inhibitory activity, was established. N-Alkylation of (2S)-2-amino-4-phenylbutyric acid ester (12) with 3-((2R)-2-methane or toluenesulfonyloxypropionyl)-2-oxoimidazolidine derivative (11) diastereoselectively proceeded in an SN2 fashion to afford tert-butyl (4S)-3-[(2S)-2-[N-[(1S)-1-ethoxycarbonyl)-3-phenylpropyl]amino]propionyl]-1-methyl-2-oxoimidazolidine-4-carboxylate (13), a precursor of 1. Alternatively, benzyl (2S)-2-[N-(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]amino]propionate (15), which is the key building block of 13,was synthesized by teh same strategy. This procedure was also applied to the synthesis of enalapril.

Journal

• Chemical & pharmaceutical bulletin

  Chemical & pharmaceutical bulletin 39 (6), 1374-1377, 1991-06-25

  The Pharmaceutical Society of Japan

Keywords

• ACE inhibitor
• imidapril
• enalapril
• recemization
• diastereoselective synthesis

Details

• CRID: 1570009752554819200
• NII Article ID: 110003629346
• NII Book ID: AA00602100
• ISSN: 00092363
• Text Lang: en
• Data Source:
  • CiNii Articles