Synthesis and porcine pancreatic elastase inhibitory evaluation of 6α-(sulfonyl)oxy-and 6α-chloropenicillanate sulfone esters and 3α-(acyloxy)methyl-6α-chloropenam sulfones

The synthesis of 6α-chloropenicillanate sulfone esters 4a-c, 9, the acetate and benzoate of 3α-hydroxymethyl-6α-chloropenam sulfones 6a-b and pivaloyloxymethyl and benzyl esters of several 6α-(sulfonyl)oxypenicillanate sulfones 12, 15a1-a3, 15b1-b3 are reported. When tested as inhibitors of porcine pancreatic elastase, the acetate of 3α-hydroxymethylpenam 6a proved to be more active in comparison with the esters of 3α-carboxylic acid counterparts 4a-c and 9. Compounds with diverse 6α-(sulfonyl)oxy substituents showed elastase inhibitory activity improved over the corresponding 6α-chloro derivatives 4a-c and 9; among those, compounds 15a2 and 15b2 were rather unstable, but compounds 15a1, 15a3, 15b1, 15b3 combined fair activity with better stability.