Cephem 1,1-dioxide

A catalytic amount of palladium on charcoal (5 mol %) has been shown by Stoodley to effect allylic oxidation of cephem dioxides and (81) in yields of about 60% in each case. ... 

A related oxidative rearrangement of cephem dioxides has been reported in which an alkene is oxidized stereospecifically with rearrangement to the allylic alcohol in good yield by simple exposure to a palladium/caibon catalyst, as depicted in equation (12). Adventitious oxygen preadsotbed on the catalyst seems the likely oxida The reaction fails on the parent ccphem or its monoxide, or on the free acid of the dioxide. This reaction would seem to hold some promise for furdier utility in the cephem field and odier related systems. 

Pyrolytic methods involve the use of dithiolane S, S -dioxides as starting materials which, upon heating, afford reactive thioaldehydes, such as trifluorothioacetaldehyde, trapped as the Diels-Alder adduct369,370 (equation 82). In equation 80 an enethiolate was formed, and this feature has been employed also in the cleavage of the oxathiolane 78. The silver vinylthiolate 79 thus obtained was applied in the preparation of new antibacterial cephem derivatives371. 

The synthesis and inhibitory activity toward human leukocyte elastase of new 7a-methoxy and 7a-chloro (2-acyloxymethyl)cephem derivatives have been reported <2001EJM185>. Starting from 4-(/frt-butylcarbonyl)-7/3-amino-3-methyl-A3-cephem 1,1-dioxide 37, a practical and efficient route leading to the synthesis of 4-(/frt-butyl-carbonyl)-7a-methoxy-3-methyl-A3-cephem 1,1-dioxide 38, a key intermediate in the preparation of potent inhibitors of mammalian serine proteinases, has been reported <1998SL322>. The new synthetic pathway has allowed easy access to an array of 7-substituted cephem derivatives such as 39 and 40 (Scheme 6). 

The carbonyl-carbonyl reductive condensation could not be reproduced on simple non-P-lactam models [82b], but worked on other iV-oxaloazetidinones, which were successfully condensed to carbapenem [82a, 162] and cephem-1,1-dioxide products [170]. 

High-pressure hydrogenation of methyl-7-phenoxyacetamido-3-methyl-3-cephem-4-carboxylate 1,1-dioxide (43) leads to compounds 44 and 45. The abnormal C-4 stereochemistry in 45 was evidenced by a five-bond coupling between the a axial C-4 and C-7 protons in the NMR spectrum not observed in 46. Further, strong base treatment of 45 resulted in epimerization at C-4 to give the more stable a-carbonyl configuration in compound 46. On the basis of these experiments, it was concluded that... 

Starting with the same 3-formyl-2-cephem intermediate (244), Peter and co-workers (1975) were also able to make 3-carboxy-3-cephem and its derivatives. Thus, direct oxidation of the 3-formyl group with sodium cyanide and manganese dioxide provided the 3-methoxycarbonyl-2-ce-phem which was isomerized to the 3-cephem-4-carboxylic acid and 3-carboxy-3-cephem-4-carboxylic acid by known methods. 

---