Synthesis and antibacterial activity of new 1,2,3-triazolylmethyl-2H-1,4-benzothiazin-3(4H)-one derivatives

A novel series of 1,2,3-triazole derivatives containing 1,4-benzothiazin-3-one ring (7a-9a, 7b-9b), (10a-12a, 10b-12b) and (13-15) were synthesized by 1,3-dipolar cycloaddition reactions of azides α-D-galactopyranoside azide F, 2,3,4,6-tetra-O-acetyl-(D)-glucopyranosyl azide G and methyl-N-benzoyl-α-azidoglycinate H with compounds 4-6.

Initially, the reactions were conducted under thermal conditions in ethanol. The reaction leads, each time, to the formation of two regioisomers: (Schemes 2, 3) with yields of 17 to 21% for 1,5-disubstituted 1,2,3-triazole-regioisomers (7b-12b) and yields ranging from 61 to 65% for the 1,4-disubstituted regioisomers (7a-12a). In order to report an unequivocal synthesis of the 1,4-regioisomers and confirm the structures of the two regioisomers obtained in thermal conditions (Huisgen reactions), the method click chemistry (Copper-Catalyzed Azide-Alkyne Cycloaddition) has been used.

The newly synthesized compounds using cycloaddition reactions were evaluated in vitro for their antibacterial activities against some Gram positive and Gram negative microbial strains. Among the compounds tested, the compound 8a showed excellent antibacterial activities against PA ATCC and Acin ESBL (MIC = 31.2 μg/ml).