Aminohydroxamic acids

In 1975, SAR studies involving actinonin investigated an analogue in which the orientation of the Pl -P2 amide bond was reversed (13), but the compound was found to lack antibacterial activity. Since then, however, descriptions of some /i-aminohydroxamic acids and /i-amino-A-formyl-A-hydroxylamines as PDF inhibitors have appeared in the patent literature. Patent applications from Senju [97] and De Novo [98] pharmaceuticals cover Pl -P2 amides (14), ureas (15, 16) and sulfonamides (17). 

In aqueous solution, depending on pH, Q-aminohydroxamic acids having no competing donor system in a side chain (like glycinehydroxamic acid or alaninehydroxamic acid, H2L) form different complex species with Ni11 ions. The major complexes are the NiL, and [NiL( 11L)]... 

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... 

HYDROXYPYRAZINE 1-OXIDES FROM a-AMINOHYDROXAMIC ACIDS AND 1,2-DICARBONYL COMPOUNDS OR a,P-UNSATURATED a-BROMOALDEHYDES... 

In an attempt to force the condensation of an a-aminohydroxamic acid and a potential a-keto aldehyde to give 3,6-disubstituted 2-hydroxypyrazine 1-oxides, Dunn and co-workers (545, 546) studied the condensation of a-aminohydroxamic... 

The preparation of 3,6-disubstituted 2-hydroxypyrazine 1-oxides from (11), which were derived from a-aminohydroxamic acids and a,fl-unsaturated a-bromo-... 

Preparations of hydroxypyrazine A-oxides by primary syntheses have been included in Chapter III and are summarized briefly as follows Section 1II.3, 2-hydroxypyrazine 1-oxides from a-aminohydroxamic acids and 1,2-dicarbonyl compounds or a,/l-unsaturated a-bromo aldehydes (545-548) Section III.4, 2-hydroxy-3,6-dimethylpyrazine 1-oxide from the bisulfite derivatives of pyruvo-hydroxamic acid and aminoacetone (548) and Section III.5, ring closure of the C-C-N-C-C-N-0 system (545, 546, 548-553). In addition to these preparations... 

Some interesting transformations were described for N-substituted A-ary I hydroxyl -amines. The a-aminohydroxamic acids 180 rearranged in the presence of amines to give A - acy lo x y ary I am i n es 181 (N O transacylation)273 (equation 71). 

This type of synthesis has been used extensively in the preparation of hydroxamic acids resembling aspergillic acid. a-Aminohydroxamic acids react35 86 with a-dicarbonyl compounds to yield pyrazine hydroxamic acids (18). Glyoxal and diacetyl react readily, but poor... 

The action of nitrous acid on o-aminohydroxamic acids gave products that are believed39 to be triazine hydroxamic acids, e.g., 28. These gave a red color with ferric chloride, and 28 was converted by sodium hydroxide into o-azidobenzoic acid (29). 

A-Oxides are also prepared by primary construction from oximes, as exemplified by the synthesis of 2-aminopyrazine 1-oxides from aminomalononitrile tosylate and a-oximinoketones (Scheme 37). Some other syntheses of A-oxides from a-functionalized oxime derivatives are available . Analogues of aspergillic acid, l-hydroxy-2(li7)-pyrazinones, are prepared by condensation of a-aminohydroxamic acids with 1,2-dicarbonyl compounds <49JCS2707> or alternatively of a-oxohydroxamic acids with a-aminoketones <50JCS3409> (Scheme 47). 

Aminohalides s. Halogenamines N-Amino-N-heterocyclics N-deamination 26, 480 reactions with lead tetraacetate 26,480 o-Amino-N-heterocyclics ring closures with - 13, 535 a-Aminohydroxamic acids... 

Cyclic hydroxamic acids from o-aminohydroxamic acids... 

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