Harold Monro Moody

Penicillin acylase-catalyzed synthesis of ampicillin in "aqueous solution-precipitate" systems. High substrate concentration and supersaturation effect

Abstract Penicillin acylase-catalyzed ampicillin synthesis via acyl group transfer in aqueous solution is highly dependent on the initial substrate concentration. The solubility of one substrate, 6-aminopenicillanic acid (6-APA), can be advantageously enhanced by the presence of acyl donor, the second substrate. Furthermore, a comparison of enzymatic synthesis in homogeneous solution with synthesis in a heterogeneous system having partially undissolved reactants, reveals major advantages for the latter approach. In this “aqueous solution–precipitate” system, accumulation of both products, ampicillin and d -(−)-phenylglycine, proceeds through the formation of their supersaturated solutions. Subsequent precipitation of the product ampicillin positively influences the efficiency of the biocatalytic process. As a result, ampicillin synthesis proceeds in 93% conversion on 6-APA and in 60% conversion on d -(−)-phenylglycine methyl ester.

Resolution of (RS)-phenylglycinonitrile by penicillin acylase-catalyzed acylation in aqueous medium

A new strategy for the biocatalytic resolution of (R,S)-phenylglycinonitrile, a crucial intermediate in the antibiotic industry, has been developed. While former techniques exploit nitrilases or combinations of nitrile hydratases and amidases, manipulating with nitrile functionality, the current approach is based on a highly efficient and enantioselective acylation of the α-amino group with phenylacetic acid catalyzed by a well known enzyme, penicillin acylase from E. coli, in slightly acidic aqueous medium. It is shown that since the condensation product is poorly soluble, removal of (S)-phenylglycinonitrile from the reaction sphere is almost complete and irreversible, favoring kinetics of the process and making high conversion possible. The proposed approach is characterized by high space-time yield and extends the scope of enzymatic synthesis in aqueous medium.

Synthesis of enantiomerically pure 2,2-disubstituted-2-amino-ethanols by dissolving metal reduction of a,a-disubstituted amino acid amides

Abstract Enantiomerically pure 2,2-disubstituted 2-amino-ethanols are prepared in 65 – 99% yield by reduction of a , a -disubstituted amino acid amides using liquid sodium metal in refluxing 1-propanol.

Chemo-enzymatic synthesis of (S)-(+)-cericlamine and related enantiomerically pure 2,2-disubstituted-2-aminoethanols

The synthesis of (S)-(+)-cericlamine (S)-1 and related disubstituted amino alcohols is described as an example of the stereoselective synthesis of amino alcohols from disubstituted amino acids and their corresponding amides. Thus, the amino alcohols (S)-1, (R)-6 and (S)-7 are prepared from enantiomerically pure α-methyl-3,4-dichlorophenylalanine (amide), (R)-4 and (S)-5, respectively, by application of the recently developed sodium–propan-1-ol or NaBH4–H2SO4 reduction method followed by reductive alkylation. (R)-4 and (S)-5 were prepared by phase transfer catalysis and subsequent enzymatic hydrolysis of racemic 4 using an amidase from Ochrobactrum anthropi.