Dsm N.v.

Gist-brocades B.v.

Dsm IP Assests B.v.

Wilhelmus H J Boesten

Quirinus B Broxterman

Marcus J M Plaum

Harold Monro Moody

Jacob Van Soolingen

Peter J L M Quaedflieg

Rocus M Dekkers

Wilhelmus J J Van Den Tweel

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.

Process for the preparation of ampicillin

A process is disclosed for preparing an (S)-2-amino-&ohgr;-oxoalkanoic acid derivative in which the corresponding aldehyde is converted into the corresponding acetal-protected aldehyde, the acetal-protected aldehyde is converted into the corresponding aminonitrile, the aminonitrile is converted into the corresponding amino acid amide, the amino acid amide is subjected to an enzymatic, enantioselective hydrolysis in which the (R)-enantiomer of the amino acid amide remains and the (S)-enantiomer is converted into the (S)-amino acid, and the (S)-amino acid is isolated. Preferably, the reaction mixture obtained after the conversion of the aminonitrile into the amino acid amide is treated with a benzaldehyde to form the Schiff base of the amino acid amide. The Schiff base is separated out and is converted into the free amino acid amide.

Process for preparing optically active 2-amino-w-oxoalkanoic acid

The invention relates to a process for the preparation of an antibiotic, in particular cefalexin, ampicillin, amoxicillin, cefaclor, cefradin, cefadroxil, cefotaxim and the like, wherein a beta-lactam core is acylated, the antibiotic is recovered from the reaction mixture, the remaining mother liquor is subjected to a hydrolysis reaction in which the antibiotic present in the mother liquor is decomposed into its initial compounds, in particular the beta-lactam core, and the acylation agent is hydrolized. The beta-lactam core can then be recovered virtually quantitatively or recycled to the acylation reaction. This is because it has been found that the solubility of the beta-lactam core is unexpectedly high at relatively high concentrations of acylation agent and antibiotic.

Process for the preparation of an antibiotic

A process is disclosed for preparing an (S)-2-amino-&ohgr;-oxoalkanoic acid derivative in which the corresponding aldehyde is converted into the corresponding acetal-protected aldehyde, the acetal-protected aldehyde is converted into the corresponding aminonitrile, the aminonitrile is converted into the corresponding amino acid amide, the amino acid amide is subjected to an enzymatic, enantioselective hydrolysis in which the (R)-enantiomer of the amino acid amide remains and the (S)-enantiomer is converted into the (S)-amino acid, and the (S)-amino acid is isolated. Preferably,the reaction mixture obtained after the conversion of the aminonitrile into the amino acid amide is treated with a benzaldehyde to form the Schiff base of the amino acid amide. The Schiff base is separated out and is converted into the free amino acid amide.

Process for preparing optically active 2-amino-&ohgr;-oxoalkanoic acid derivatives

Method for preparing a salt of aspartylphenylalanine methyl ester from N-protected aspartylphenylalanine methyl ester involving cleaving off the protective group by treatment with an acid, in the course of which, first of all, N-protected aspartylphenylalanine methyl ester is caused to react in an aqueous medium and in the presence of methanol at a temperature of from 0 to 80&deg; C. with from 0.8 to 2 equivalents of acesulphamic acid for at least such a time that the conversion to the salt of aspartylphenylalanine methyl ester and acesulphamic acid has been completed to an adequate degree, and then the salt formed in the first step is isolated in precipitated form at a temperature of 30&deg; C. or lower.

Method for preparing salts of aspartame from N-protected aspartame

A process is disclosed for the esterification of an amino acid or peptide in which the amino acid or peptide is converted into the corresponding ester in the presence of a hydrosulphate have the general formula ROSO,H, where R represents an alkyl group, with the hydrosulphate being prepared, in the presence of the amino acid or peptide, from chlorosulphonic acid and an alcohol having the general formula ROH, where R has the same meaning as above. The chlorosulphonic acid to amino acid or peptide molar ratio preferably is between 0.8 and 2.0, in particular between 1.0 and 1.3. A primary alcohol, in particular methanol, is preferably used as alcohol. The amino acid used may be for example an &agr;-amino acid chosen from the group comprising p-hydroxyphenylglycine, phenylglycine, phenylalanine, tyrosine, proline and valine; L-alanyl-L-proline or an ester of L-aspartyl-L-phenylalanine, for example, may be used as peptide.

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Sittard, Netherlands

Wilhelmus H J Boesten