J. C. Kapur

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.

Non-hazardous synthesis of isocephosphorin intermediates via α-vinylamino-β-lactams☆

Abstract The reaction of a Schiff Base derived from veratrylamine and cinnamaldehyde with (α-methyl-β-alkoxycarbonyl)-vinylamino acetic acid (from glycine and an acetoacetate ester) in presence of a chloroformate ester and triethylamine constitutes a safe synthesis of α-vinylamino β-lactams that can be converted by literature methods to known intermediates for the synthesis of isocephalosporins and analogs.

Studies on lactams—XXVII : Synthesis and reactions of 4-carboxy-β-lactam☆

Abstract Reaction of phenoxyacetyl chloride with α-carbomethoxybenzylidine- p -anisidine 1 in presence of triethylamine gave a mixture of E and Z 1-( p -anisyl)-4-carbomethoxy-3-phenoxy-4-phenyl-2-azetidinones 2 which upon hydrolysis with lithium iodide in refluxing pyridine produced the corresponding acids in the ratio of 3:1. A series of substituted β-lactams were prepared by transforming the carboxy group of the E-isomer into the acid chloride, amide, cyano, acid azide, isocyanate, urethane, urea, hydroxymethyl, aldehyde, acetoxy and methoxy groups.

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.