Benzotriazole-mediated synthesis of aza-peptides: en route to an aza-leuenkephalin analogue

J Org Chem. 2013 Apr 19;78(8):3541-52. doi: 10.1021/jo302251e. Epub 2013 Apr 10.

Abstract

Novel N-(N-Pg-azadipeptidoyl)benzotriazoles 20a-e couple efficiently with α-amino acids 21a-e, dipeptides 22a-c, aminoxyacetic acid 23a, depsidipeptide 23b, and α-hydroxy-β-phenylpropionic acid 27 yielding, respectively, azatripeptides 24a-g, azatetrapeptides 25a,b, a hybrid azatripeptide with an oxyamide bond 26a, a hybrid azatetrapeptide with an ester bond 26b, and a hybrid azatripeptide with an ester bond 28. A new protocol for the synthesis of N-Pg-azatripeptides 33a,b and 35a,b, each containing a natural amino acid at the N-terminus, avoids the low coupling rates of the aza-amino acid residue and enables the solution-phase synthesis of an azaphenylalanine analogue of Leu-enkephalin 40.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acids / chemical synthesis*
  • Amino Acids / chemistry*
  • Aza Compounds / chemical synthesis*
  • Aza Compounds / chemistry
  • Dipeptides / chemical synthesis*
  • Dipeptides / chemistry
  • Enkephalin, Leucine / chemical synthesis*
  • Enkephalin, Leucine / chemistry*
  • Molecular Structure
  • Peptides / chemical synthesis*
  • Peptides / chemistry*
  • Propionates / chemical synthesis*
  • Propionates / chemistry
  • Triazoles / chemistry*

Substances

  • Amino Acids
  • Aza Compounds
  • Dipeptides
  • Peptides
  • Propionates
  • Triazoles
  • alpha-hydroxy-beta-phenylpropionic acid
  • Enkephalin, Leucine
  • benzotriazole