Concise enantiospecific, stereoselective syntheses of (+)-crispine A and its (-)-antipode

J Org Chem. 2011 Mar 18;76(6):1605-13. doi: 10.1021/jo102112k. Epub 2011 Feb 22.

Abstract

An enantiospecific and stereoselective total synthesis of the natural product (+)-crispine A has been demonstrated employing a Pictet-Spengler bis-cyclization reaction between commercially available (R)-(-)-methyl 2-amino-3-(3,4-dimethoxyphenyl)propanoate and 4-chloro-1,1-dimethoxybutane to preferentially provide the cis tricyclic adduct. Decarboxylation by a convenient two-step protocol provided the enantiopure natural product in three steps with an overall isolated yield of 32% from the amino acid. The unnatural antipode (-)-crispine A was similarly prepared in three steps from the commercially available (S)-(+)-amino acid.

MeSH terms

  • Biological Products / chemical synthesis
  • Biological Products / chemistry
  • Isoquinolines / chemical synthesis*
  • Isoquinolines / chemistry*
  • Stereoisomerism
  • Substrate Specificity
  • Tyrosine / chemistry

Substances

  • Biological Products
  • Isoquinolines
  • crispine A
  • Tyrosine