Synthesis of 3-Substituted-clavams: Antifungal Properties, DD-Peptidase and beta-Lactamase Inhibition.
The [2+2]cycloaddition of chlorosulfonyl isocyanate to vinyl and (Z)-propenyl ethers derived from the 2-O-sulfonylated (R)- and (S)-1-(furyl-2')-1,2-ethanediols furnished the 4-alkoxy-azetidin-2-ones with a good to moderate stereoselectivity. The intramolecular alkylation of the beta-lactam nitrogen atom led to the corresponding 3-(furyl-2')- and 6-methyl-3-(furyl-2')-clavams. The transformation of the furyl residue into an alkoxycarbonyl group led to clavams related to the natural compounds. The synthesized clavams exhibited moderate inhibitory activities against DD-peptidase 64-575 and beta-lactamase (penase) as well as antifungal activities.
Cierpucha
Maciej
M
Institute of Organic Chemistry of the Polish Academy of Sciences, Warsaw, Poland.
Panfil
Irma
I
Danh
Tong Thanh
TT
Chmielewski
Marek
M
Kurzatkowski
Wieslaw
W
Rajnisz
Aleksandra
A
Solecka
Jolanta
J
D000478:Alkylation; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D002855:Chromatography, Thin Layer; D002969:Clavulanic Acids / Q000737:chemistry*; D003500:Cyclization; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D065093:beta-Lactamase Inhibitors
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D002969:Clavulanic Acids; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D011480:Protease Inhibitors; D065093:beta-Lactamase Inhibitors; C483963:clavam; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase