Synthesis of sulfonopeptides

Abstract

Sulfonopeptides as the sulfur analogues of natural peptides have been widely used as enzyme inhibitors due to their tetrahedral sulfonamide moiety, which can mimic the transition-state analogues of hydrolysis of the ester and amide bonds. Synthetic methods of sulfonopeptides are reviewed. The synthetic methods of sulfonopeptides include the condensation of N-protected amino acid/peptide acids and 2-aminoalkanesulfonic acids, coupling of N-protected 2-aminoalkanesulfonyl chlorides and amino acid esters/peptide esters, sulfinylation of amino acid esters/peptide esters with N-protected 2-aminoalkanesulfinyl chlorides and subsequent oxidation, the alkylation of taurine-containing peptides, and the displacement of N-aminoacyl/peptidyl 2-aminoalkyl halides/methanesulfonates with sulfites. Hybrid sulfonophosphinopeptides are prepared through the Mannich-type reaction of N-protected 2-aminoalkanesulfonamides/peptidylsulfonamides, aldehydes, and aryldichlorophosphines/phosphorus trichloride followed by the aminolysis with amino acid/peptide esters or hydrolysis. The developed synthetic methods provide diverse synthetic routes for biologically important sulfonopeptides as the candidates of medicinal agents.

Keywords: aminoalkanesulfonic acid; sulfinopeptide; sulfonopeptide; α-sulfonopeptide; β-sulfonopeptide.