Asymmetric synthesis and antimicrobial activity of some new mono and bicyclic beta-lactams.
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 beta-lactam 6 as a single stereoisomer. Ozonolysis of 6 followed by reduction with lithium aluminum tri(tert-butoxy) hydride afforded the hydroxymethyl beta-lactam 8. Treatment of 8 with methansulfonyl chloride gave the mesylated monocyclic beta-lactam 9, which was converted to the bicyclic beta-lactam 10 upon treatment with 1,8-diazabicyclo[5,4.0] undec-7-ene (DBU). Deprotection of the phthalimido group in beta-lactams 6 and 10 by methylhydrazine and subsequent acylation of the free amino beta-lactams with different acyl chlorides in the presence of pyridine afforded mono and bicyclic beta-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.
Jarrahpour
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Chemistry Department, College of Sciences, Shiraz University, Shiraz 71454, Iran. jarrah@susc.ac.ir
Shekarriz
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Taslimi
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D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D008997:Monobactams / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001643:Bridged Bicyclo Compounds; D008997:Monobactams