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.