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Cα-methyl phenylglycine-based semi-synthetic ampicillin and cephalexin analogues

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Summary

Reaction of the N-carboxyanhydride from Cα-methyld-phenylglycine with either 6-aminopenicillanic acid or 7-amino-3-desacetoxy-cephalosporanic acid furnishes the corresponding ampicillin and cephalexin analogues. Neither the biological activity nor the chemical stability of these new semi-synthetic antibiotics are superior to those of their unmethylated counterparts.

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Abbreviations

Phg:

phenylglycine

(αMe)Phg:

Cα-methyl phenylglycine

NCA:

N-carboxy anhydride (Leuchs' anhydride or 1,3-oxazolidine-2,5-dione)

6-APA:

6-amino-penicillanic acid

7-ADCA:

7-amino-3-desacetoxycephalosporanic acid

AMPI:

ampicillin

CEX:

cephalexin

OMe:

methoxy

MeOH:

methanol

EtOH:

ethanol

ButOH:

butanol

AcOH:

acetic acid

EtOAc:

ethyl acetate

MeCN:

acetonitrile

UV:

ultraviolet

IR:

infrared

NMR:

nuclear magnetic resonance

HPLC:

high-pressure liquid chromatography

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Authors and Affiliations

  1. Biopolymer Research Centre, C.N.R., Department of Organic Chemistry, University of Padova, I-35131, Padova, Italy

    Eric Mossel, Fernando Formaggio, Marco Crisma & Claudio Toniolo

  2. DSM Research, Organic Chemistry and Biotechnology Section, P.O. Box 18, 6160 MD, Geleen, The Netherlands

    Theo Sonke, Eric C. Roos & Quirinus B. Broxterman

  3. DSM Fine Chemicals, 6401 JH, Heerlen, The Netherlands

    Johan Kamphuis

Authors
  1. Eric Mossel
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  2. Fernando Formaggio
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  3. Marco Crisma
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  4. Claudio Toniolo
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  5. Theo Sonke
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  6. Eric C. Roos
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  7. Quirinus B. Broxterman
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  8. Johan Kamphuis
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Mossel, E., Formaggio, F., Crisma, M. et al. Cα-methyl phenylglycine-based semi-synthetic ampicillin and cephalexin analogues. Lett Pept Sci 5, 43–48 (1998). https://doi.org/10.1007/BF02443539

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  • DOI: https://doi.org/10.1007/BF02443539

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