ABSTRACT
The novel bicyclic and tricyclic systems dimethyl (4aS*,6S*)-6-methoxy-7-oxo-4a,5,6,7,8,9-hexahydro-2H-benzocycloheptene-3,4-dicarboxylate, C(16)H(20)O(6), (I), dimethyl (4aS*,6R*)-6-methoxy-7-oxo-4a,5,6,7,8,9-hexahydro-2H-benzocycloheptene-3,4-dicarboxylate, C(16)H(20)O(6), (II), (3aS*,9R*,10aS*,10bR*)-9-methoxy-2-oxa-1,3a,4,6,7,8,9,10,10a,10b-decahydro-3H-cyclohepta[e]indene-1,3,8-trione, C(14)H(16)O(5), (III), and (1S*,2R*,9S*,10aR*)-9-methoxy-8-oxo-1,2,3,5,6,7,8,9,10,10a-decahydrobenzocyclooctene-1,2-dicarboxylic acid, C(15)H(20)O(6), (IV), have been crystallographically characterized, allowing the determination of the relative configuration of the stereogenic centres. The poor quality of the dicarboxylic acid crystals necessitated the use of synchrotron radiation.
ABSTRACT
Syntheses are described for penicillins (4b approximately 4i, 5a and 5b) which possess a 6 beta-(2-heteroaryl-3-substituted)-propenamido side-chain of fixed geometry. In vitro results for these compounds against a range of Gram-positive and Gram-negative bacteria showed in most cases good stability against both penicillinase and TEM-1 beta-lactamase; analogues (4b approximately 4i) bearing a 2-(2-aminothiazol-4-yl) unit showed the best intrinsic activity, the cyclohexyl compound (4b) being the most promising. The 1-acetoxyethyl ester (6) of 4b was also prepared; in experimental animal studies the in vivo properties of this compound compared favourably with cefuroxime axetil and are reported together with selected in vivo data for the other compounds.
