Acta Pharm. 51 (2001) 35-44

Syntheses and potential antibacterial activities of some new penicillins and desacetoxycephalosporins containing aspartic acid, asparagine and phenylalanine residues

VALERIU SUNEL,^1* CRISTINA BASU,² DOINA MAFTEI-SÎRBU,³ MARCEL POPA,⁴
EUGEN DIACONU² and  CAMELIA SOLDEA⁴

¹The „Al. I. Cuza" University, Iasi, Romania
²S. C. Antibiotice S. A., Iasi, Romania
³The University of Oslo, Blindern, Norway
⁴The „Ghe. Asachi" Technical University, Iasi, Romania

The aim of the present paper is the synthesis of new semisynthetic penicillins and desacetoxycephalosporins starting from oxazolinones known as highly reactive compounds towards nucleophilic reagents. By acylation of the 6-aminopenicillanic and 7-aminodesacetoxycephalosporanic acids with 2-nitrophenyl-4-beta-carboxymethyl-delta²-oxazolin-5-one, 2-nitrophenyl- 4-beta-amidomethyl-delta²-oxazolin-5-one and nitrophenyl-4-benzyl-delta²-oxazolin-5-one in aqueous and in non-aqueous media at low temperatures the corresponding antibiotics have been obtained. UV, IR and ¹H NMR spectral measurements and elemental analyses elucidated the structures of the newly synthesized compounds.
The compounds prepared exerted high antibiotic activity, although their activity spectra depend on the type of substituent. Derivatives with substituents containing a carboxylic group are less efficient against Gram-positive but highly advantageous against Gram-negative organisms.

Keywords: acylation, aminoacid derivatives, penicillins, cephalosporins, antibacterial activity, oxazolones