Synthesis, biological, and chiroptical activity of 3-phenyl-clavams.
The [2+2]cycloaddition of chlorosulfonyl isocyanate to simple vinyl ethers derived from the 2-O-sulfonylated (R) and (S) 1-phenyl-1,2-ethanediol leads to 4-alkoxy-azetidin-2-ones with a moderate stereoselectivity. The cycloaddition to analogous (Z)-propenyl ethers proceeds stereospecifically with the retention of the olefin configuration. The intramolecular alkylation of beta-lactam nitrogen atom furnished all possible stereoisomers of 3-phenyl- and 6-methyl-3-phenyl-clavams. The biological and chiroptical activity of synthesized clavams was investigated. The (3R,5R)-diastereomer 30 showed higher inhibition of bacterial enzymes than other related compounds.
Cierpucha
Maciej
M
Institute of Organic Chemistry of the Polish Academy of Sciences, 01-224 Warsaw, Poland. chmiel@icho.edu.pl
Solecka
Jolanta
J
Frelek
Jadwiga
J
Szczukiewicz
Patrycja
P
Chmielewski
Marek
M
D001419:Bacteria / Q000201:enzymology; D001671:Biochemistry / Q000379:methods*; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors; D002969:Clavulanic Acids / Q000737:chemistry* / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D065093:beta-Lactamase Inhibitors
C492853:(3R,5R) 3-phenyl-clavam; D002969:Clavulanic Acids; D004791:Enzyme Inhibitors; D065093:beta-Lactamase Inhibitors; C483963:clavam; D002268:Carboxypeptidases; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase