.beta.-Thionolactam analogs of cephalosporins and penicillins

Evidence for an oxyanion hole in serine β-lactamases and dd-peptidases

“….65 (1H, dd, J = 4.3 and 8.6 Hz, H-7), 7.0-7.4 (SH, m, Ar) and 7.27 (1H, d, J = 7.9 Hz, NH)] and i.r. spectrum (absence of 8-lactam C=O and presence of C=S stretching vibrations) agreed with those reported in the literature [23]. Also isolated from the second column were the 7-(phenoxythioacetamido)cephalosporin (30 mg, 0.40 yield) and the dithionated material (0.9 g, 11 O yield).…”

“…2,2,2-Trichloroethyl 7-(phenoxyacetamido)-8-thiono-3'-desacetoxycephalosporanate was prepared by a modification of the procedure of Wojtkowski et al [23]. The 8-oxo analogue, prepared as described above (7.6 g, 15.8 mmol), and 3.8 g of boron sulphide (Alfa) were stirred in 50 ml of dry chloroform at 0°C for 7 h. The solution was then heated under reflux until no starting material remained (approx.…”

“…Finally, 7-(phenoxyacetamido)-8-thiono-3'-desacetoxycephalosporanic acid (1Ib) was obtained as a yellow solid in 65 % yield on deprotection of the 2,2,2-trichloroethyl ester by zinc and acetic acid [23]. Fast-atombombardment m.s.…”

Thionation of bicyclic ß-lactam compounds by Lawesson’s reagent

“…Considering that the best yield reported for the synthesis of a 7-thioxopenicillin was 1%, 6 we decided to test the reaction of a series of penicillins with LR ( Figure 2). Generally speaking, penicillins demonstrated to be less reactive than cephalosporins to LR.…”

.GAMMA.-Lactam analogues of .BETA.-lactam antibiotics.

“…Our work continued with the synthesis and biological evaluation of fused y-lactam azetidines34-35) since molecular modelling studies of these molecules showedsimilar pyramidal distortions of the lactam nitrogen atom to those observed in penicillins. The degree of pyramidal distortion of the lactam nitrogen in /Mactam antibiotics has been associated with antibacterial activity.36) Bromination of glutaric anhydride (13) and transformation to the diester (16) was followed by cyclisation with benzylamine to give the diastereomeric azetidines (17) (Scheme 2). Sodium borohydride reduction provided the alcohols (18) separable by fractional crystallisation.…”