An Efficient and Regioselective Route Towards Novel 1,2,3-Triazole (Isoxazole)-Linked 1,3-Thiazolidine Hybrids via a Copper-Catalyzed Alkyne-Azide Reaction

Abstract

A clean and highly regioselective three-step synthetic procedure to obtain two new series of novel 1,3-thiazolidine/1,2,3-triazole hybrids (3a–r and 5a–f) based on the copper-catalyzed alkyne-azide reaction (CuAAC) was developed. The key intermediaries, the 3-propioloyl-thiazolidine-4-carboxylic acid methyl esters (2a–e) and methyl 3-propargyl-thiazolidine-4-carboxylic acid methyl ester (4) were easily prepared from the corresponding thiazolidine-4-carboxylic acid methyl esters (1a–e), which were previously obtained from L-(+)-cysteine and some aromatic and aliphatic aldehydes with subsequent acylation reaction activated by carbodiimide with propiolic acid or the respective alkylation reaction using propargyl bromide. In addition, one new thiazolidine/isoxazole hybrid (6a) was also obtained through 1,3-dipolar cycloaddition reaction with the same click chemistry approach. All of the molecular hybrids reported here are promising models for future pharmacological studies, particularly for the development of cancer drugs, with a special focus on in vitro prostate cancer models.