Lactams oxidation

Although the mechanism(s) of p-lactam-induced nephrotoxicity is not fully elucidated, there is growing evidence that for some of the p-lactams, oxidative stress plays a pivotal role in the chain of events leading to nephrotoxicity and cell death [10, 34, 40]. 

Also, lactams could be hydroxylated [223] or alkoxylated [224,225] in the a-position. In the case of five- and six-membered A-alkyl lactams oxidation occurs regioselectively at the endocyclic carbon in a-position to nitrogen and at the exocyclic a-carbon with seven-... 

Murahashi reported a similar oxidation using Fe203 catalyst on a number of simple substrates in 56-98% yield and on a very important carbapenam intermediate 54.31 Keto-lactam oxidation of 53 provided 54 in 93% yield with retention of... 

Cyclic compounds capable of undergoing ring opening (alkylene oxides, lactones, lactams, anhydrides, etc.). 

In some cases where there is a neighboring group participation effect, aldehydes are formed. The a-vinyl group in the / -lactam 29 is mainly oxidized to aldehyde 30[83],... 

Oxidative cleavage of P-aminoacyl complexes can yield P-amino acid derivatives (320,321). The rhodium(I)-catalyzed carbonylation of substituted aziridines leads to P-lactams, presumably also via a P-aminoacyl—metal acycHc compound as intermediate. The substituent in the aziridine must have 7T or electrons for coordination with the rhodium (322,323). 

Lead sesquioxide is used as an oxidation catalyst for carbon monoxide ia exhaust gases (44,45) (see Exhaust control), as a catalyst for the preparation of lactams (46) (see Antibiotics, P-lactams), ia the manufacture of high purity diamonds (47) (see Carbon, diamond-natural), ia fireproofing compositions for poly(ethylene terephthalate) plastics (48), ia radiation detectors for x-rays and nuclear particles (49), and ia vulcanization accelerators for neoprene mbber (50). 

Bromine can oxidize certain tertiary amines to lactams (33). 

Cephalosporin 5-oxides and penicillin 5-oxides (221) can be converted into isothiazol-3-ones (222) by the action of bases. These reactions proceed via an intermediate azetidinonesulfenic acid (223 Scheme 37) (77SST(4)339). Attempts to prepare /3-lactam compounds from isothiazoles have, as yet, been unsuccessful (81X2181). 

Other interactions of /3-lactams with electrophiles include the oxidative decarboxylation of the azetidin-2-one-4-carboxylic acid (85) on treatment with LTA and pyridine (81M867), and the reaction of the azetidin-2-one-4-sulfinic acid (86) with positive halogen reagents. This affords a mixture of cis- and trans-4-halogeno-/3-lactams (87), the latter undergoing cyclization to give the bicyclic /3-lactam (88) (8UOC3568). 

There appear to be few examples of the formation of azetidin-2-ones by closure of the C(2) —C(3) bond. One reaction which fits into this category involves reaction of the iron carbonyl lactone complexes (144) with an amine to give the allyl complexes (145) which on oxidation are converted in high yield to 3-vinyl-/3-lactams (146) (80CC297). 

Oxidative ring expansion occurs when the hydrazine (175) is treated with manganese dioxide (73TL4091). Diphenylcyclopropenone (176) reacts with ammonia and methylamine to give /3-lactams (69BCJ1777). Initial attack could occur at either C-1 or C-2 of the cyclopropenone. 

A variety of mono- and bi-cyclic /3-lactams have also been prepared by oxidative ring contraction of pyrrolidine-2,3-diones (180) (75JOC2356), and by the photolysis of pyrazolidin-3-ones (181) (78T1731, 75JOC3510, 75JOC3502, 75CC725). 

At Smith Kline French a general approach to cephalosporin and penicillin nuclear analogs was developed that utilizes a monocyclic /3-lactam (59) with the correct cis stereochemistry as a key intermediate. This is prepared by reaction of the mixed anhydride of azidoacetic acid and trifluoroacetic acid with imine (58) followed by oxidative removal of the dimethoxybenzyl group. This product could be further elaborated to intermediate (60) which, on reaction with a -bromoketones, provides isocephalosporins (61). These nuclear analogs displayed antibacterial properties similar to cephalosporins (b-79MI51000). 

The TBDMS derivative of a /3-lactam nitrogen is reported to be stable to lithium diisopropylamide, citric acid, Jones oxidation, and BH3-diisopropylamine, but not to Pb(OAc)4 oxidation. 

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