Enantioselective synthesis of (2-pyridyl)alanines via catalytic hydrogenation and application to the synthesis of L-azatyrosine

Org Lett. 2001 Oct 4;3(20):3157-9. doi: 10.1021/ol016455q.

Abstract

[reaction: see text] A novel method for the synthesis of (2-pyridyl)alanines 2a-b was developed by converting (2-pyridyl)dehydroamino acid derivatives 1a-b to the corresponding N-oxides 3a-b followed by asymmetric hydrogenation using (R,R)-[Rh(Et-DUPHOS)(COD)]BF(4) [(R,R)-6] catalyst and subsequent N-oxide reduction in 80-83% ee. This methodology was applied to the total synthesis of L-azatyrosine [(+)-12], an antitumor antibiotic, starting from (5-benzyloxy)-2-pyridylmethanol (7), in >96% enantiomeric purity.

MeSH terms

  • Alanine / analogs & derivatives
  • Alanine / chemical synthesis*
  • Antibiotics, Antineoplastic / chemical synthesis*
  • Catalysis
  • Hydrogen / chemistry
  • Pyridines / chemical synthesis*
  • Stereoisomerism

Substances

  • 2-pyridyl alanine
  • Antibiotics, Antineoplastic
  • Pyridines
  • beta-(5-hydroxy-2-pyridyl)alanine
  • Hydrogen
  • Alanine