title: Application of the Barton photochemical reaction in the synthesis of 1-dethia-3-aza-1-carba-2-oxacephem: a novel agent against resistant pathogenic microorganisms.
abstract: Racemic 7-(phenylacetamido)-1-dethia-3-aza-1-carba-2-oxacephem 3 was synthesized and found to possess antibacterial activity against Staphylococcus aureus FDA 209P, Escherichia coli ATCC 39188, Pseudomonas aeruginosa 1101-75 and Klebsiella pneumoniae NCTC 418 as well as the beta-lactamase producing organisms E. coli A9675 and P. aeruginosa 18S-H and the methicillin-resistant organism S. aureus 95. Formation of the carbacephem 3 originated from the Barton photochemical reaction in the conversion of 8 to 10. Intramolecular cyclization of syn-oximino beta-lactam 10 afforded 7-azido-2-oxa-3-azacephem 11, which was reduced and acylated to 12. Enzymatic removal of the methyl group from 12 gave the target molecule 3.
authors.affiliation: Institute of Chemistry, Academia Sinica, TaiGen Biotechnology, Taipei, Taiwan, R. O. C. hosein@taigenbiotech.com.tw
authors.forename: Gholam Hossein
authors.initials: GH
authors.lastname: Hakimelahi
authors.forename: Pai-Chi
authors.initials: PC
authors.lastname: Li
authors.forename: Ali A
authors.initials: AA
authors.lastname: Moosavi-Movahedi
authors.forename: Jamshid
authors.initials: J
authors.lastname: Chamani
authors.forename: Ghadam Ali
authors.initials: GA
authors.lastname: Khodarahmi
authors.forename: Tai Wei
authors.initials: TW
authors.lastname: Ly
authors.forename: Famil
authors.initials: F
authors.lastname: Valiyev
authors.forename: Max K
authors.initials: MK
authors.lastname: Leong
authors.forename: Shahram
authors.initials: S
authors.lastname: Hakimelahi
authors.forename: Kak-Shan
authors.initials: KS
authors.lastname: Shia
authors.forename: Ito
authors.initials: I
authors.lastname: Chao
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000737:chemistry; D024881:Drug Resistance, Bacterial; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D007536:Isomerism; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000235:genetics; D008712:Methicillin / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams / Q000737:chemistry / Q000494:pharmacology
chemical_list: C479361:1-dethia-3-aza-1-carba-2-oxacephem; D000890:Anti-Infective Agents; D002511:Cephalosporins; D004791:Enzyme Inhibitors; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D008712:Methicillin