Epimerization-free block synthesis of peptides from thioacids and amines with the Sanger and Mukaiyama reagents

Angew Chem Int Ed Engl. 2009;48(13):2355-8. doi: 10.1002/anie.200805782.

Abstract

Highly activated thioesters formed by the rapid reaction of C-terminal thioacids derived from protected amino acids and peptides with the Sanger reagent and other electron-deficient aryl halides in the presence of a free amine immediately form a peptide bond with the amine. This essentially epimerization-free method was used for the 4+4 block synthesis of a hindered octapeptide (see scheme; Boc, Pbf, and Trt are protecting groups).

MeSH terms

  • Amines / chemistry*
  • Amino Acid Sequence
  • Amino Acids / chemistry
  • Peptides / chemical synthesis*
  • Peptides / chemistry
  • Sulfhydryl Compounds / chemistry*
  • Sulfur Compounds / chemistry

Substances

  • Amines
  • Amino Acids
  • Peptides
  • Sulfhydryl Compounds
  • Sulfur Compounds
  • thioacetic acid