Hydroxamic acid esters cyclic

Lactones, which may be regarded as cyclic or inner esters, react similarly. Anhydrides of carboxylic acids also react with hydroxylamine to form hydroxamic acids ... 

Perhaps the most reliable method for the reductive cyclization of a nitro ester to a hydroxamic acid is that which involves treatment with sodium horohydride in the presence of palladium on charcoal. Although under these conditions aromatic nitro compounds are reduced to amines, o-nitro esters such as 53, in which the ester group is suitably oriented with respect to the nitro group, give good yields of cyclic hydroxamic acids (54). Coutts and his co-... 

Hydroxamic acids constitute an important class of siderophores, which play a major role in iron solubilization and transport. Some of them are important as therapeutic agents. The Michael addition of nitroacetyl proline esters to allyl acrylate followed by Pd(0)-catalyzed intramolecular allyl transfer and subsequent reduction of the nitro group yields a novel class of cyclic hydroxamic acids related to pyroglutamic acid (Scheme 5.9).85... 

Pratasine. The utilisation of the cyclic hydroxamic acid 230 as a late precursor of pratosine has also been described [62] (Scheme 38). The preparation of 230 was achieved in excellent yield by photocyclisation of the borate ester 231 itself obtained from hydroxamic acid 232. Aqueous hydrolysis of the cyclic borate furnished 230, which underwent a smooth Michael addition to methyl propiolate to form the O-vinyl ester 233. The latter, on thermolysis in wet dimethylsulfoxide provided, via a 3,3-sigmatropic rearrangement, pratosine (204, 17% yield) and methyl pratosine-4-carboxylate (234,35% yield). 

By retro synthetic analysis collagenase inhibitor RO0319790 (1) can be assembled from two chiral building blocks, (R) -succinate 2 and (S)-tert-leucine N-methyla-mide 13. As the latter can be prepared from commercially available (S)-tert-leucine 8 our work concentrated in particular on the construction of the first building block 2. In order to assemble the carbon skeleton of 2 in the most efficient way, extremely cheap maleic anhydride 4 was converted in a known ene reaction with isobutylene to provide the cyclic anhydride 6. Hydrogenation of the double bond followed by the addition of EtOH/p-TsOH yielded the racemic diethyl ester substrate 9 for the enzyme reaction. The enzymatic monohydrolysis of 9 afforded the monoacid (R)-2a. (R)-2 a was coupled via its acid chloride with leucine amide 13 to ester 14, which finally was converted into the hydroxamic acid 1. 

Cyclic hydroxamic acids are formed by partial reduction of A -(nitrophenyl)gly-cine in an acidic medium at 60 C. The glycine ester (72.6) may be heated with a base to give the dione. 

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.). 

Methoxy-4-nitropyridazines react with alkyl iodides at about 100°C to give esters of cyclic hydroxamic acids [Eq. (23)] resulting from methylation, demethylation, and nitro group displacement. A 6-methyl group is transformed into a cyano group by the nitrous acid produced.432... 

Peptide antibiotics. Antibiotics with linear or cyclic oligopeptide structures containing not only L- amino acids but often also unusual, non-proteinogenic amino acids. Homopeptides are built up exclusively of amino acids (e.g., gramicidins), the so-called heteropeptides also contain other structural elements, e.g., hydroxamic acids. Macrocyclic Ra. containing one or more ester bonds in the ring are known as peptide lactones (e.g., hormaomycin) or depsipeptides (e.g., valinomycin). 

Cyclic hydroxamic acids from nitrocarboxylic acid esters O... 

Figure 1 Representative siderophores of the hydroxamate and catecholate classes. The hydroxamates are synthesized from the amino acid ornithine that has been modified through hydroxylation and acetylation. Ferrichrome (a) is a prototypical example of the tri-hydroxamate class. Structurally, ferrichrome is a cyclic hexapeptide that consists of three modified ornithine residues (each of which has a hydroxamate side chain) and three glycines. Ferrichrome coordinates ferric iron through its three bidentate hydroxamate side chains. Triacetylfusarinine C (b) is also a cyclic tri-hydroxamate, but the three modified ornithine residues are joined by ester linkages rather than by peptide linkages. Ferrioxamine B (c) is a linear tri-hydroxamate consisting of three peptide-huked modified ornithine residues. Enterobactin (d) is a prototypical example of a catecholate siderophore. It consists of a tri-ester ring from which extend three side chains of chhydroxybenzoyl serine. Each of these siderophores binds ferric iron in a hexadentate manner, which results in full saturation of d orbitals and a very stable complex. Ferric forms are shown in (a) and (b). Desferri-forms are shown in (c) and (d)...

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