A convenient synthesis of α-amino-β-lactams

Ajay K. Bose, M. S. Manhas, J. M. van der Veen, S. G. Amin, I. F. Fernandez, K. Gala, R. Gruska, J. C. Kapur, M. S. Khajavi, J. Kreder, L. Mukkavilli, B. Ram, M. Sugiura, J. E. Vincent

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Abstract

A safe and convenient method is described for the synthesis of α-amido-β-lactams starting with glycine and an azomethine. The amino group of glycine is protected by reaction with a β-dicarbonyl compound following the method of Dane et al. and the carboxyl group is activated through the formation of a mixed anhydride or an active ester. Condensation between these glycine derivatives and acyclic or cyclic imino compounds (including thioimidates) in presence of triethylamine leads to stereospecific synthesis of 3-(β-carbonyl-vinylamino)-2-azetidinones in 40-60% yield. The vinylamino side chain can be hydrolyzed under mild acid conditions to form 3-amino-2-azetidinones which can be acylated to α-amido-β-lactams. Alternatively, the vinylamino side chain can be converted to an amido side chain by ozonolysis. The molecular parameters of a 3-(β-carbonyl-vinylamino)-2-azetidinone were determined by X-ray crystallography. Usefulness of this α-amido-β-lactam synthesis is illustrated by the preparation of isotopelabeled β-lactams and intermediates for some β-lactam antibiotics.

Original languageEnglish (US)
Pages (from-to)2321-2334
Number of pages14
JournalTetrahedron
Volume37
Issue number13
DOIs
Publication statusPublished - 1981

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Cite this

Bose, A. K., Manhas, M. S., van der Veen, J. M., Amin, S. G., Fernandez, I. F., Gala, K., ... Vincent, J. E. (1981). A convenient synthesis of α-amino-β-lactams. Tetrahedron, 37(13), 2321-2334. https://doi.org/10.1016/S0040-4020(01)88885-2