S. G. Amin

α-Substituted β-Lactams via a Convenient Annelation of Imines

Abstract In 1966 Bose and co-workers2 introduced azidoacetyl chloride as a valuable reagent for β-lactam synthesis by the “acid chloride-imine method.”3 The azido group serves as a crypto amino function for further elaboration of the penicillin and cephalosporin side chain. The use of this reagent in β-lactam chemistry has proved very fruitful; the synthesis of trans penicillin V methyl ester,4 cephalosporins,5 penicillin,5 4-mercapto-2-azetidinones,6 and other β-lactams have been achieved in various laboratories through the intermediacy of this reagent. Azidoacetyl chloride, like other azido compounds, however, tends to decompose with explosive violence if rigorous precautions are not observed. We have been engaged, therefore, in exploring alternative synthetic approaches to β-lactams which would make the use of azidoacetyl chloride unnecessary. In the present communication we wish to report a facile method for the preparation of α-azido-β-lactams and other 3-substituted-2- azetidinones without employing...

A CONVENIENT SYNTHESIS OF α-AMINO-β-LACTAMS

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.

Studies on lactams. Part 45. Some carbocyclic analogues of cephalosporin

Several polycyclic β-lactams have been synthesized by the reactions of cyclic imines with acid chlorides in the presence of triethylamine. The azido-functions in these β-lactams were reduced to amino-groups, which were then acylated with phenylacetyl chloride to introduce the penicillin G side chain. Some carbocyclic analogues of cephalosporin were found to possess antibacterial activity.