Hydroxamic acids oxidation structures

No simple pteridine 1- or 3-oxides are yet known. If the AT-atom of an amide function is formally oxidized, tautomerism favours the cyclic hydroxamic acid structure, as found for 3-hydroxypteridin-4-one (55JA3927), 1-hydroxylumazine (64JOC408) and 2,4-diamino-8-hydroxypteridin-7-ones (75JOC2332). 

Palamidessi and Bernardi have obtained 2-chloropyrazine 1-oxide by mild treatment of pyrazine 1,4-dioxide with phosphoryl chloride. The structure of the 1-oxide was confirmed by hydrolysis to 2-hydroxy-pyrazine 1-oxide, which was also prepared by direct synthesis from glyoxal and glycine hydroxamic acid.398 This synthesis is illustrative of a general method for preparing 2-hydroxypyrazine 1-oxides by condensation of a,/3-dicarbonyl compounds with a-aminohydroxamic acids. An analogous synthesis of 2-aminopyrazine 1-oxides has already... 

Oxidation of deferrialbomycin S2 with performic acid cleaves the hydroxamic acid linkages and converts the bound NS-hydroxyomithine to glutamic acid, the latter still in peptide combination. Partial acid hydrolysis and identification of fragments affords the structure cyclo-(seryl)s-(glutamyl)3 (135). The oxygen of the side chain of the first serine is linked via sulfur to N1 of 3-methylcytosine, which in turn is acylated with an unknown fragment. 

On principle, both the hydroxamic acid and the hemiacetal are partially oxidised structures. Thus, the hydroxamic acid should be accessible both fi-om a nitro precursor by reductive cyclisation and from a lactam by N-oxidation (Fig. (7)). Similarly, access to the hemiacetal should e.g. be possible by oxidation of a 2-methylene group as well as by reduction of a 2-carbonyl group, and also by hydrolysis of a 2-haIogen function. The influence of substituents at the aromatic ring on the synthesis of the 1,4-benzoxazinone ring is hardly foreseeable. However, another circumstance has a very rational basis. Due to the fact that the structural instability arises from the cyclohemiacetal (see Fig. (4)) this tmit is prepared at the very end of most syntheses. 

Oxidation of diene-containing hydroxamic acids has been reported to give acylnitroso species which undergo spontaneous hetero-IMDA reactions to give heterobicyclic ketones. (E,E)-N-Hydroxy-5,7-dodecadienamide, upon treatment with tetrapropylammonium periodate, gave the pyrido[l,2-b][l,2]oxazine structure in high yield88. 

Enantiomerically pure manganese complexes using ligands other than the salen structure have been reported, but so far with lower enantioselectiv-ities. Better results have been achieved using molybdenum complexes bearing hydroxamic acid ligands and TBHP or cumylhydroperoxide as oxidant. This system has been used to effect the epoxidation of a range of olefins with up to 96% ee. 

Shea s group applied this type 2 A-acylnitroso intramolecular Diels-Alder cyclization to the synthesis of tricyclic BCD core of stenine. The C2-tethered cyclic diene 103 was converted to the corresponding hydroxamic acid by treatment with NH20H-HC1, which, upon oxidation with BU4NIO4, was converted to 104 as a 6 1 mixture of diastereomers. Reductive N-0 bond cleavage of 104 yielded the alcohol 105 and its diastereomer (not shown). Further elaboration of 105 provided the tricyclic core structure 106 of stenine (Scheme 4.22) [41],... 

It has been generally demonstrated that pyrazine 1-oxides are biologically active but that the deoxy derivatives are not. The hydroxamic acid moiety of these compounds is probably a major structural requirement for the exhibition of their biological activity, because the compounds containing the hydroxamic acid moiety show an antibiotic effect on microorganisms and a convulsive effect on animals. The naturally occurring fungal pyrazine 1-oxides are shown in Table II. 

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