o-Phthalyl amidase in the synthesis of loracarbef: Process development using this novel biocatalyst |
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Authors: | Black Thomas D. Briggs Barbara S. Evans Robert Muth William L. Vangala Surya Zmijewski Milton J. |
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Affiliation: | (1) Lilly Research Laboratories, Process Research and Development, 46285 Indianapolis, Indiana, USA |
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Abstract: | Summary A dephthalylation step utilizing a novel enzyme, o-phthalyl amidase, was developed. This step was part of a potentially new large scale synthetic route for a novel beta-lactam antibiotic Loracarbef. The enzyme was isolated from the organism Xanthobacter agilis. Purification of the enzyme to near homogeneity was accomplished by a 3-step procedure. Studies indicated that the phthalimido group can be opened chemically to generate the o-phthalyl derivative. This enzyme then can remove the phthalyl group from o-phthalylated amides. Optimization of the process was achieved by combining these two hydrolysis steps. Conversion yields of 85–97.8% (mol/mol) were obtained from reactions at substrate concentrations of 5–10% (w/v). |
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