Degradation of beta-lactamase inhibitor, (2S,3R,5S)-3-methyl-7-oxo-3-(1H-1,2,3-triazol-1-yl-methyl)-4-thi a-1- azabicyclo[3.2.0]heptane-2-carboxylic acid 4,4-dioxide (YTR-830H), in aqueous solutions and alkaline methanol solution: pathway and structural elucidation of products.

Abstract

(2S, 3R, 5S)-3-Methyl-7-oxo-3-(1H-1, 2, 3-triazol-1-yl-methyl)-4-thia-l-azabicyclo [3.2.0]-heptane-2-carboxylic acid 4, 4-dioxide (YTR-830H) is a new β-lactamase inhibitor. The degradation of this β-lactamase inhibitor in several buffer solutions, NaOH aqueous solution and NaOH-saturated methanol solution was investigated. In the initial step of degradation in aqueous solutions, YTR-830H was degraded to 2-amino-3-methyl-3-sulfino-4-(1H-1, 2, 3-triazol-1-yl)-butyric acid (YTR-830H-II) and formylacetic acid (YTR-830H-III) through (E)-5-methyl-5-sulfino-6-(1H-1, 2, 3-triazol-l-yl)-3-aza-l-heptene-1, 4-dicarboxylic acid (YTR-830H-I) as an intermediate. The YTR-830H-II in all solutions then proceeded to an unidentified product, YTR-830HIIa. In acidic solution it was converted to 1, 2, 3-triazole and several unidentified products (YTR-830H-IIa, -IIb, -IIc and-IId). Degradation at various pHs showed different patterns and rates. Following degradation in NaOH-saturated methanol solution, 1-methyl hydrogen (E)- and (Z)-5-methyl-5-sulfino-6-(1H-1, 2, 3-triazol-1-yl)-3-aza-1 -heptene-1, 4-dicarboxylic acid (YTR-830H-Ia and Ib) were detected.