The Effect of 2-Mercapto-5-Methyl-1,3,4-Thiadiazole on Enzymatic Synthesis of Cefazolin |
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Authors: | J I Won C G Kim J H Kim J H Lee Y J Jeon |
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Institution: | (1) Cheil Jedang Corp., R & D Center, 522-1 Dokpyongri Majangmyon, Ichonsi, 467- 810 Kyonggido, Korea |
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Abstract: | The effect of unreacted residual 2-mercapto-5-methyl-l,3,4-thiadiazole (MMTD), the reagent for 3-5-methyl-l,3,4-thiadiazole-2-yl]-7-aminocephalosporanic
acid (M-7-ACA) synthesis, on the enzymatic acylation of M-7-ACA by the methyl ester of 1,2,3,4-tetrazol-1-acetic acid (MeTzAA)
to produce cefazolin (CEZ) was studied. In the two-step process of synthesizing CEZ from 7-aminocephalosporanic acid (7-ACA),
one of the key parameters controlling the overall CEZ yield was the ratio of MMTD to 7-ACA in M-7-ACA synthesis. The increase
of the ratio showed opposing effects by increasing the M-7-ACA yield in the first step, while decreasing CEZ yield in the
subsequent enzymatic reaction by the inhibitory effect of the increased content of MMTD as an impurity in the M-7-ACA preparation.
It was revealed that the decrease of CEZ yield in the enzymatic reaction was caused by the selective retardation of the rate
of CEZ synthesis reaction by a typical competitive inhibition, while not affecting the rate of MeTzAA hydrolysis reaction.
The optimum MMTD-to-7-ACA ratio rendering the highest overall CEZ yield over 7-ACA was 1.2:1. |
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Keywords: | Cefazolin enzymatic synthesis kinetics inhibition 2-mercapto-5-methyl-l 3 4-thiadiazole 7-aminocephalosporanic acid |
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