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.
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.
Hakimelahi
Gholam Hossein
GH
Institute of Chemistry, Academia Sinica, TaiGen Biotechnology, Taipei, Taiwan, R. O. C. hosein@taigenbiotech.com.tw
Li
Pai-Chi
PC
Moosavi-Movahedi
Ali A
AA
Chamani
Jamshid
J
Khodarahmi
Ghadam Ali
GA
Ly
Tai Wei
TW
Valiyev
Famil
F
Leong
Max K
MK
Hakimelahi
Shahram
S
Shia
Kak-Shan
KS
Chao
Ito
I
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
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