Thio‐α‐amino acids (S‐acids) as a carboxyl component in peptide synthesis catalysed by papain

Abstract

Peptide synthesis catalysed by papain was studied using thio‐α‐amino acids (S‐acids) as a carboxyl component. It was found, for example, that with Z‐AlaSH (pK 2.70) the maximal yield of the peptide Z‐AlaValNH2 was obtained at pH 8–8.5. A two‐fold excess of Z‐AlaSH furnished peptides with yields close to 100%. Thio‐amino acids with bulky side groups, for example, Z‐IleSH, Z‐Asp(OBut)SH, gave peptides with a low yield. Papain interacts with Z‐AlaSH better than do bromelain or ficin.

One-Pot Syntheses of Dissymmetric Diamides Based on the Chemistry of Cyclic Monothioanhydrides. Scope and Limitations and Application to the Synthesis of Glycodipeptides

“…Monothiocarboxylic acids [RC(O)SH] have an interesting and varied chemistry, some of the more fascinating aspects of which pertain to their use in amide bond forming reactions. Such amide bond forming reactions include the direct coupling of thioacids with amines, their condensation with azides, their condensation with electron-deficient sulfonamides, again leading to amides, their use as precursors to thioesters for native chemical ligation, and their application as components of Ugi-type reactions leading to thioamides . Monoselenocarboxylic acids undergo analogous reactions, as do dithioacids albeit with the provision of thioamides in the latter case. ,, Despite the obvious utility of this broad range of chemistry thioacids have found relatively little application in organic synthesis, perhaps due to the very limited range of commercially available thioacids and the consequent need to prepare all but the simplest members of the family.…”

Synthesis of Peptide Thioacids at Neutral pH Using Bis(2-sulfanylethyl)amido Peptide Precursors

“…Using these conditions, thiocarboxylate 6a was isolated in 45% yield (52% corrected, entry 1, Table ). Note that the purification of thiocarboxylates 6a – e was carried out by HPLC using triethylamine–acetate pH 6.5 buffer, which to the contrary of 0.1% TFA water/acetonitrile eluent preserves the peptide thiocarboxylates from partial degradation during the lyophilization step . Figure shows the LC–MS analysis of the crude thiocarboxylate 6e as a typical example.…”

Cyclic Thioanhydrides: Linchpins for Multicomponent Coupling Reactions Based on the Reaction of Thioacids with Electron-Deficient Sulfonamides and Azides

“…Thioacids are useful intermediates in organic synthesis, having found application in peptide synthesis, and as precursors to thioesters for native chemical ligation . Their long-established reaction with azides yields secondary amides and has recently come to the fore as a versatile ligation reaction, while their complementary reaction with 2,4-dinitrobenzenesulfonamides 5 has been much less widely applied.…”