Process for the preparation of ampicillin
AssigneeDSM IP Assests B.V.
InventorsHarold M. Moody, Wilhelmus H. J. Boesten
Life of this patent
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Abstract
Ampicillin is produced in a batch process by enzymatic acylation of 6-aminopenicillanic acid (6-APA) with the aid of phenylglycine derivative such as D-phenylglycine amide. High conversions of phenylglycine derivative may be achieved by having the total concentration in the reaction mixture of 6-APA and ampicillin greater than 250 mM and the molar ration of total quantity of phenylglycine derivative to total quantity of 6-APA less than 2.5. Higher yields of ampicillin may be achieved when the amount of dissolved 6-APA is kept low, e.g. below 300 mM.
Claims10
A process for preparation of ampicillin comprising:
- acylating 6-aminopenicillanic acid (6-APA) with a phenylglycine derivative and an enzyme to form a reaction mixture wherein the process is carried out while
- i) the total concentration in the reaction mixture of 6-APA and ampicillin combined is substantially throughout the reaction, greater than 250 mM;
- ii) metering in partially the 6-APA and/or the phenylglycine derivative in the course of the acylation reaction to thereby maintain the concentration of dissolved 6-APA lower than 300 mM throughout the reaction;
- and
- iii) the molar ratio of the total quantity of phenylglycine derivative to the total quantity of 6-APA is less than 2.5.
A process for the preparation of ampicillin by acylating a quantity of 6-aminopenicillanic acid (6-APA) with a quantity of phenylglycine derivative and an enzyme in an aqueous reaction medium to provide a reaction mixture containing dissolved 6-APA;
- said process comprising
- initially introducing a part of said quantity of the 6-APA and/or a part of the quantity of phenylglycine derivative into the reaction medium under conditions allowing ampicillin to be formed by the acylation reaction and,
- thereafter adding the rest of the quantity of 6-APA and/or phenylglycine derivative, under conditions whereby ampicillin will continue to be formed by the acylation reaction, and
- wherein the concentration of dissolved 6-APA in the reaction mixture is, throughout the acylation reaction, lower than 300 mM and the total combined concentrations in the reaction mixture of 6-APA and formed ampicillin is greater than 250 mM;
- and further
- wherein the molar ratio of the quantity of phenylglycine derivative to the quantity of 6-APA is less than 2.5.
Dependencies are inferred from the claim text.