Asymmetric Synthesis and Antimicrobial Activity of Some New Mono and Bicyclic β-Lactams

Abstract

Abstract:Reaction of the amino acid D-phenylalanine ethyl ester (4) with cinnamaldehyde gave chiral Schiff base 5, which underwent an asymmetric Staudinger [2+2] cycloaddition reaction with phthalimidoacetyl chloride to give the monocyclic β-lactam 6 as a single stereoisomer. Ozonolysis of 6 followed by reduction with lithium aluminum tri(tert-butoxy) hydride afforded the hydroxymethyl β-lactam 8. Treatment of 8 with methansulfonyl chloride gave the mesylated monocyclic β-lactam 9, which was converted to the bicyclic β-lactam 10 upon treatment with 1,8-diazabicyclo[5,4.0] undec-7-ene (DBU). Deprotection of the phthalimido group in β-lactams 6 and 10 by methylhydrazine and subsequent acylation of the free amino β-lactams with different acyl chlorides in the presence of pyridine afforded mono and bicyclic β-lactams 14a-d and 15a-d respectively. The compounds prepared were tested against Escherichia coli, Staphilococcus citrus, Klebsiella pneumanie and Bacillus subtillis. Some of these compounds showed potential antimicrobial activities.

Novel and Recent Synthesis and Applications of β-Lactams

“…Monocyclic b-lactams with R = PhtN, PhCH 2 COHN, PhOCH 2 COHN were highly active against Bacillus subtilis and moderately active against Staphylococcus citrus. Other compounds were all inactive against these four pathogenic microorganisms [92].…”

“…Reaction of D-phenylalanine ethyl ester with cinnamaldehyde has been reported to give a chiral Schiff base, that underwent an asymmetric Staudinger [2+2] cycloaddition reaction with phthalimidoacetyl chloride to give the monocyclic b-lactam as a single stereoisomer. Ozonolysis of this latter followed by reduction with lithium aluminum tri(tert-butoxy)hydride has produced the hydroxymethyl-blactam, that was converted to the bicyclic b-lactam upon treatment with metansulfonyl chloride and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), (Scheme 29), [92]. a-Amino-b-lactams have been reported to be prepared via Staudinger-like [2+2] cycloaddition of N,N-dialkylhydrazones to a-aminoketenes [93].…”

“…The same group of Jarrahpour has also synthesized a few mono and bicyclic b-lactams (Fig. 33) and tested their antimicrobial activity [92].…”

Synthesis, biological screening and molecular modeling studies of novel 3-chloro-4-substituted-1-(2-(1H-benzimidazol-2-yl)phenyl))-azetidin-2-ones

“…This irreversible inhibition of the PBPs prevents the final cross linking (transpeptidation) of the nascent peptidoglycan layer, disrupting cell wall synthesis 3 . Benzimidazoles and their analogs are well known biologically active N-containing heterocycles 4 . Specifically, the 2-substituted analogs of benzimidazoles are known to be potent biologically active compounds 5 .…”

Synthesis of Novel N-Sulfonyl Monocyclic β-Lactams as Potential Antibacterial Agents

“…The discovery of the nocardicins, 1, and monobactams, 2, demonstrated for the first time that β-lactams do not require a conformationally constrained bicyclic structure to have antibacterial properties [9], suggesting that the biological activity was strictly correlated to the presence of a suitably functionalized 2-azetidinone ring [10]. In addition to the monobactams and nocardicins, some other monocyclic β-lactams such as compounds 3 [11], 4 [12], and 5 [13] have also shown good antibacterial activity. Cyclic sulfonamides have been shown to be highly useful heterocycles in medicinal chemistry [13].…”