Hydroxamic acid esters lactams

As in 10-55 hydrazides and hydroxamic acids can be prepared from carboxylic esters, with hydrazine and hydroxylamine, respectively. Both hydrazine and hydroxylamine react more rapidly than ammonia or primary amines (the alpha effect, p. 445). Imidates, RC(=NH)OR, give amidines, RC(=NH)NH2. Lactones, when treated with ammonia or primary amines, give lactams. Lactams are also produced from y- and 5-amino esters in an internal example of this reaction. 

Using this pulse sequence to estimate the nature of derivatization of Suwannee River fulvic acid with N-enriched hydroxylamine to leam more about the carbonyl functionality of fulvic acid, Thom et al.(76) obtained signals for the primary products as oximes. Additional signals of secondary products arising from Beckmann rearrangements of the initial oxime derivatives were identified as nitriles, secondary amides and lactams. The bands assigned to hydroxamic acid result from a reaction of esters with NH2OH and are evidence for the presence of esters in the fulvic acid. 

Cephalothin can be determined by means of the colored complex formed on the addition of a ferric reagent to the corresponding hy-droxamic acid produced by treatment with hy-droxylamine. The method used is essentially the same.as the procedure described for penicillins. The ferric hydroxamate procedure is not specific for cephalothin or penicillins. For example, many amides, esters, and anhydrides form hydroxamic acids when reacted with hydroxyl-amine. This type of interference is eliminated by the blank determination wherein cephalothin is rendered incapable of forming hydroxamic acid by use of basic hydrolysis or enzymatic hydrolysis with cephalosporinase. Since cephalothin degradation products having an intact (3-lactam ring react as well as the parent compound, the method measures total 3-lactam content. ... 

Photochemical transpositions of steroids into the naphtho[2,1-f]quinoline system include a low-yielding photo-Beckmann (H.Suginome and T. Uchida, Bull, chem Soc. Japan, 1974, f , 687) and the conversion of 17-nitrite esters to the 17-a hydroxamic acids, reduction of which affords the lactam (S.H. Imam and B.A. Marples, Tetrahedron Letters, 1977, 2613). 

Classical reactions involving nucleophiles such as saponification ("OH as the nucleophile), aminolysis (with amines also ammonia in ammonolysis reactions), transesterification (alkoxides, "OR) and others (hydrazinolysis, hydroxamic acid synthesis, etc.) have been adapted to solid phane and used to obtain, for instance, carboxylic acids, amides and esters. Internal or intramolecular nucleophilic attack has been employed to obtain cyclic products such as lactones, lactams (including cyclic peptides) and a great variety of heterocycles (hydantoins, diketopiperazines, benzodiazepinones, etc.). 

The majority of reported solid-phase combinatorial syntheses of the lactam core utilize a [2-i-2] cycloaddition reaction of ketenes with resin-bound imines [33-41]. A further development of the Staudinger reaction was reported by Mata and coworkers using Mukaiyama s reagent [42]. In addition, a stereoselective synthesis of chi-rally pure P-lactams has been performed as a first utilization of polymer-supported oxazolidine aldehydes [43]. Other strategies include an ester enolate-imine condensation [44], an Hg(OCOCF3)2-mediated intramolecular cydization [45], and Miller hydroxamate synthesis [46]. Because of the variability derived from the scaffold synthesis, not many attempts have been made to derivatize the resin-bound lactam template [47]. One of the most detailed descriptions of a versatile (3-lactam synthesis on a resin employed amino acids tethered as esters on Sasrin resin [48]. 

Among the most suitable methods for the synthesis of appropriately substituted monocyclic P-lactams [16], the chlorosulphonylisocyanate-alkene approach, the acid chloride-imine method, the ester enolate-imine condensation and the hydroxamate approach have received considerable attention in P-lactam synthesis. 

The common methods for the S5mthesis of p-lactams are cycloaddition reactions such as the Staudinger s ketene-imine cycloadditions, ester enolate-imine cycloadditions, alkyne-nitrone cycloadditions (Kinugasa reaction), alkene-isocyanate cycloadditions, and Torii s cyclocarbonylation of allyl halides with imines. Several cyclizahon reactions of p-amino esters, p-amino acids, p-hydroxamate esters, and a-diazocarbonyls have been developed for the formation of p-lactam ring. N,N-Disubstituted a-haloamides cyclize by C3-C4 bond formation leading to the formation of P-lactam ring. 

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