Studies on Amino Acids and Peptides, 13 Improved Synthesis of 5‐Thioxo‐L‐proline and of Some N‐Acyl and S‐Alkyl Derivatives as Building Blocks in Peptide Synthesis

We herein report an improved synthetic pathway to 5-thioxo-L-proline (2) (using R,S nomenclature, the L form here possesses the S configuration). Compound 2 is synthesized from naturally occurring 5-oxo-L-proline (1) at room temperature with 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide (3) (Lawesson′s reagent, LR). The synthesis is an improved version of our previously published method. The optical purity of 2 has been proven by thin-layer chromatography based on chiral ligand exchange. The synthesis of N-acyl and S-alkyl derivatives of 5-thioxo-L-proline (Top-OH), 5-thioxo-L-proline methyl ester (Top-OCH3), and the pseudodipeptide Boc-L-Phe-Top-OCH3 is also described.