Hydroxamic acids release

When Jencks reacted hydroxylamine with p-nitrophenyl acetate, p-nitrophenolate ion was released at a rate faster than that at which acetohydroxamic acid was formed. This burst effect is evidence for a two-step reaction. In this case the intermediate is O-acetylhydroxylamine, which subsequently reacts with hydroxylamine to form the hydroxamic acid. 

More recently, an additional approach to preventing TNF toxicity has been proposed. Several metalloprotease inhibitors (most notably hydroxamic acid) prevent proteolytic processing (i.e. release) of TNF-a from producer cell surfaces. Such inhibitors may also prove useful in preventing TNF-induced illness. The extent to which TNF (and inhibitors of TNF) will serve as future therapeutic agents remains to be determined by future clinical trials. 

In general, C-acyl nitroso compounds-9,10-dimethylanthracene cycloadducts derived from hydroxamic acids (-R = alkyl, aryl, ti/2 = 4.1 h for -R = -Ph at 60°C) decompose more slowly than those derived from N-hydroxycarbamates or N-hydroxyureas [11, 13, 14]. Further addition of alkyl groups to the N atom of N-hydroxyurea-derived cycloadducts produces a further increase in the rate of the retro-Diels-Alder reaction of these cycloadducts [36]. These general trends suggest the possibility of the development of acyl nitroso compound-9, 10-dimethylanthracene cycloadducts as a general class of HNO or NO donors with varied release profiles. 

Acidolytic treatment using DCM hexafluoroisopropanoI (1 1) for 2 h at ambient temperature afforded the hydroxamic acid in only 45% yield. However, it is worth noting that the tethered Fmoc-N(Pr)-<9-2-chIorotrityI polystyrene, on treatment with similar acidolytic cocktail effected quantitative release of Fmoc-N(Pr)-OH. 

Hence, the implication of combinatorial chemistry for high throughput generation of structurally diverse hydroxamic acids is self-evident. Several solid-phase approaches for their syntheses have been reported,1 7-11 the majority of which are based on the anchoring of iV-hydroxyphthalimide onto an appropriate solid support. After hydrazine-mediated /V-dcprotcction, /V-acylation of the resin-bound hydroxylamine would yield the desired O-anchored hydroxamic acid, which is typically released by acidolysis. 

In conclusion, we anticipate that A-Fmoc-aminooxy-2-chlorotrityl polystyrene will prove an indispensable reagent for the solid-phase synthesis of hydroxamic acids by multiple and combinatorial approaches. Not only is its production both efficient and cost effective, but release of the assembled hydroxamic acid derivative is readily accomplished using mild acidolytic reagents. 

Hydroxamates have been observed in the water in the Bay of Quinte, a eutrophic bay of Lake Ontario, and are believed to be produced by blue-green algae (76). Simpson and Neilands (77) have identified schizokinen, a hydroxamic acid derivative of citric acid as an extracellular product of the blue-green algae, Anabaena sp. However, not all Anabaena produce hydroxamates, Walsby (78) has shown that Anabaena cylindrica releases a large pigmented, peptide-containing material which complexes iron. As yet these peptides have not been examined for ability to complex the actinides. 

A patent from Ortho disclosed naphthoylvalerohydroxamic acids which inhibit 5-HETE release from RBL-1 cells (0.1 /rM) and also showed oral activity in RAA [292], The most potent compound (51 % at 50 mg/kg) was the A-isopropyl analogue (115). Although only the hydroxamic acids inhibited 5-LO activity, simple acids and esters showed comparable RAA activity, suggesting that the hydroxamic acids yielded an anti-inflammatory carboxylic acid metabolite. 

In 2002, Couturier and coworkers investigated the possibility of using a dioxazole as an aprotic hydroxamic acid protective group. In this context, the masked hydroxamic acid could be introduced earlier in the synthesis and could perhaps be released in a single operation at the end of the sequence. 

Certain secondary metabolites are released into the environment and affect the growth and development of different species. The mode/s of action of allelochemicals are diverse, and this knowledge is essential to developmental biology. Previous experiments showed an effect on germination and radicle growth of the hydroxamic acid, 2-benzoxazolinone (BOA), a compound released by plants (mainly grasses) into the environment. Alterations of plant energy metabolism were also reported for BOA. Other effects have been noted, but there are still some doubts about the precise mode of action in the affected plants. 

Plants release allelochemicals as volatiles, leaf leachates, and root exudates. In addition, all the constituents of plant residues are eventually released into the environment through microbial decomposition. During this process, most allelochemicals lose their activity but some compounds, for example, benzoxazinoids (cyclic hydroxamic acids), can be activated after hydrolysis.1-3... 

In 75 days old rye plants, a DIBOA concentration of 128 to 423 pg / g dry weight was determined. 35- Day old rye has a potential to release 14.3 kg / ha of DIBOA [169]. Even a release of 16.2 kg DIBOA / ha from 34 day old rye was reported [170]. Fresh rye mulch containing 20 - 50 mmol / ha hydroxamic acid had only half of this concentration after 12 days, and after 121 -168 days the compound was not detectable anymore [62]. Longer lasting phytotoxic effects of the mulch should be due to the more stable decomposition product BOA. It was foimd that fall-killed Balboa rye suppressed weed biomass by 84 % compared to controls [163]. Fall planted spring killed rye mulch was able to inhibit total weed biomass by 68 -95 % [164]. Similar results were reported using rye mulch in no-till cropping systems [174]. 

The THP-based hnker can be modified in such a way as to allow fhe synthesis of hydroxamic acids 49, as outlined in Scheme 24. Linker 48 has played a role in the solid-phase synfhesis of matrix metalloproteinase inhibitors [52], Alternative linkers that yield hydroxamic acids after release have been used in connection with peptide chemistry, as well as for the preparation of combinatorial compounds [53-58]. 

Cyclic hydroxamic acids (11.50) stored in corn and wheat seedlings as their glucosides are released by a glu-... 

Therefore, linker molecules releasing the hydroxamic acid moiety are most valuable tools for the construction of targeted libraries for interactions with MMP s (Tobfe 1.7.4)... 

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