Efficient chemoenzymatic synthesis of (S)- and (R)-5-(1-aminoethyl)-2-(cyclohexylmethoxy)benzamide: key intermediate for Src-SH2 inhibitor

Bioorg Med Chem Lett. 2002 Jul 8;12(13):1735-8. doi: 10.1016/s0960-894x(02)00256-1.

Abstract

A facile chemoenzymatic synthesis of both the S and R forms of 5-(1-aminoethyl)-2-(cyclohexylmethoxy)benzamide a key intermediate of non-peptidic Src SH2 inhibitors is described. Both the enantiomers were synthesized in high optical purity (>99% ee) by reduction followed by lipase-mediated acylation of the precursor 6 in one-pot. Immobilized Pseudomonas cepacia lipase offered high degree of enantioselectivity with spontaneity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation
  • Benzamides / chemical synthesis*
  • Benzamides / chemistry*
  • Benzamides / metabolism
  • Benzoates / chemistry
  • Burkholderia cepacia / enzymology
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry*
  • Enzymes, Immobilized / drug effects
  • Lipase / chemistry
  • Lipase / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship
  • src Homology Domains
  • src-Family Kinases / antagonists & inhibitors*

Substances

  • Benzamides
  • Benzoates
  • Enzyme Inhibitors
  • Enzymes, Immobilized
  • src-Family Kinases
  • Lipase