Clavulanic acid derivs. - for use as beta-lactamase inhibitors for antibiotics

摘要

Clavulanic acid derivs. of formula (I) and their salts are new. In the formula, R is opt. esterified COOH; R1 is H, opt. etherified or acylated OH or an S contg. nucleophilic gp. Cpds. (I) inhibit beta-lactamases produced by a wide range of Gram-positive and -negative bacteris (including Enterobacter cloacae P99), and are thus useful for protecting penicillins and cephalosporins from beta-lactamase hydrolysis. They are also useful as intermediates for other clavulanic acid derivs. A typical cpd. (I) is 4-nitrobenzyl-2-ethyl-2-clavam-3-carboxylate. In an example, this was prepd. from 4-nitrobenzyl (3R, 5R, Z)-2-ethylidene-clavam-3-carboxylate (5R)-2-ethyl-2-clavam-3-carboxylic acid and its salts are specifically claimed.