J. M. Van Der Veen

Enantiospecific synthesis of β-lactams via cycloaddition

Enantiospecific synthesis of variously substituted cis-β-lactams can be achieved by the annelation of Schiff bases from optically active ketal aldehydes derived from D-threonine. Similar annelation of Schiff bases from the triphenylsilyl ether of D-threonine ester and cinnamaldehyde leads to cis-β-lactams with high diastereofacial selectivity.

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.