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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Black, T.D., Briggs, B.S., Evans, R. et al. o-Phthalyl amidase in the synthesis of loracarbef: Process development using this novel biocatalyst. Biotechnol Lett 18, 875–880 (1996). https://doi.org/10.1007/BF00154613
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DOI: https://doi.org/10.1007/BF00154613