Kinetic resolution of 1-chloro-3-(1-naphthyloxy)-2-propanol, an intermediate in the synthesis of beta-adrenergic receptor blockers

Bioorg Chem. 2003 Jun;31(3):259-69. doi: 10.1016/s0045-2068(03)00050-6.

Abstract

(R)- and (S)-1-chloro-3-(1-naphthyloxy)-2-propanol are intermediates in the synthesis of beta-adrenergic blocking agents and antihypertensive drugs such as propranolol and nadoxolol. Herein, improvement in the preparation of racemic 1-chloro-3-(1-naphthyloxy)-2-propanol generated from 1-naphthol and epichlorohydrin are reported. In addition, kinetic resolution studies have been conducted to obtain both (R) and (S)-1-chloro-3-(1-naphthyloxy)-2-propanol. These compounds were obtained in highly optically pure form by the stereoselective hydrolysis of its acyl derivatives using whole cell preparations containing enzymes from native sources. The results were compared with those obtained using commercial lipases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation
  • Adrenergic Antagonists / chemical synthesis*
  • Adrenergic Antagonists / chemistry*
  • Candida / enzymology
  • Chlorohydrins / chemistry*
  • Hydrolases / metabolism
  • Kinetics
  • Lipase / metabolism
  • Mucor / enzymology
  • Naphthalenes / chemistry*
  • Stereoisomerism

Substances

  • 1-chloro-3-(1-naphthyloxy)-2-propanol
  • Adrenergic Antagonists
  • Chlorohydrins
  • Naphthalenes
  • Hydrolases
  • Lipase