Stereoselective Organocatalyzed Synthesis of α-Fluorinated β-Amino Thioesters and Their Application in Peptide Synthesis

Angew Chem Int Ed Engl. 2016 Oct 10;55(42):13127-13131. doi: 10.1002/anie.201607146.

Abstract

α-Fluorinated β-amino thioesters were obtained in high yields and stereoselectivities by organocatalyzed addition reactions of α-fluorinated monothiomalonates (F-MTMs) to N-Cbz- and N-Boc-protected imines. The transformation requires catalyst loadings of only 1 mol % and proceeds under mild reaction conditions. The obtained addition products were readily used for coupling-reagent-free peptide synthesis in solution and on solid phase. The α-fluoro-β-(carb)amido moiety showed distinct conformational preferences, as determined by crystal structure and NMR spectroscopic analysis.

Keywords: cinchona alkaloids; fluorine; organocatalysis; thioesters; β-amino acids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry*
  • Catalysis
  • Crystallography, X-Ray
  • Esters / chemical synthesis*
  • Esters / chemistry
  • Halogenation
  • Models, Molecular
  • Molecular Conformation
  • Peptides / chemical synthesis*
  • Peptides / chemistry
  • Quinidine / analogs & derivatives
  • Quinidine / chemistry*
  • Stereoisomerism
  • Sulfhydryl Compounds / chemical synthesis*
  • Sulfhydryl Compounds / chemistry

Substances

  • Amides
  • Esters
  • Peptides
  • Sulfhydryl Compounds
  • Quinidine