Stereoselective syntheses of 4-hydroxy 4-substituted glutamic acids

J Org Chem. 2005 Jun 10;70(12):4569-77. doi: 10.1021/jo040296h.

Abstract

The 4-hydroxy 4-substituted glutamic acid moiety is a common substructure of biologically important natural products such as monatin [(2S,4S)-2], lycoperdic acid (3), and dysiherbaine (4). To develop methodology for syntheses of these natural products, cycloadditions of nitrone 5 with 2-substituted 2-propen-1-ols 6 and 2-substituted acrylates 8 were investigated. Reactions of nitrone 5 with alcohols 6 in the presence of MgBr2OEt2 gave cycloadducts 7 in a highly stereoselective manner, whereas noncatalyzed reactions of 5 with acrylates 8 afforded adducts 9. Using the former reaction, syntheses of monatin [(2S,4S)-2], monatin derivative 18, and lycoperdic acid (3) were accomplished. The C4-epimer of monatin [(2S,4R)-2)] was also synthesized by employing the latter cycloaddition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / analogs & derivatives*
  • Alanine / chemistry
  • Bridged Bicyclo Compounds, Heterocyclic / chemistry
  • Catalysis
  • Cyclization
  • Glutamic Acid* / analogs & derivatives*
  • Glutamic Acid* / chemical synthesis
  • Glutamic Acid* / chemistry
  • Indicators and Reagents
  • Indoles / chemistry
  • Molecular Structure
  • Stereoisomerism

Substances

  • 4-hydroxy-4-(indol-3-ylmethyl)glutamic acid
  • Bridged Bicyclo Compounds, Heterocyclic
  • Indicators and Reagents
  • Indoles
  • dysiherbaine
  • Glutamic Acid
  • Alanine