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.