Hydroxamic adds

Ester formation. Heat under very efficient reflux 1 ml. of diethyl ether, 4 ml. of glacial acetic acid and i ml. of cone. H2SO4 for ro minutes. Distil off 2 ml. of liquid. Use a few drops of this liquid for the hydroxamic add test for esters (p. 334). Use the remainder for other tests for esters (p. 354). 

Yan, C., Xiu, Z., Li, X., Li, S., Hao, C. and Teng, H. (2008) Comparative molecular dynamics simulations of histone deacetylase-hke protein Binding modes and free energy analysis to hydroxamic add inhibitors. Proteins,... 

Schafer, S., Saunders, L., Schhmme, S., Valkov, V, Wagner, J., Kratz, F. et al. (2009) Pyridylalanine-containing hydroxamic adds as selective HDAC6 inhihitors. ChemMedChem, 4, 283—290. 

The group at Pharmacyclics developed a related phenyl hydroxamic add HDACi, PCI-34051 (27e) and demonstrated this to display greater than 200-fold selectivity for HDAC8 (IC5o = 10nM) over the other HDAC isoforms [40b]. Interestingly, this compound induced caspase-dependent apoptosis in T-cell lymphomas and leukemias at low micromolar concentrations, but not in other hematopoietic or solid tumor cell lines. Furthermore, PCI-34051 does not cause detectable tubulin or histone acetylation. 

Richon, V.M. (2006) Cancer biology mechanism of antitumour action of vorinostat (suberoylanilide hydroxamic add), a novel histone deacetylase inhibitor. British Journal of Cancer, 95. S2—S6. 

Komatsu, Y, Tomizaki, K., Tsukamoto, M., Kato, T, Nishino, N., Sato, S. et al. (2001) Cyclic hydroxamic-add-containing peptide 31, a potent synthetic histone deacetylase inhibitor with antitumor activity. Cancer Research, 61, 4459 466. 

FIGURE 4. Histograms showing distributions of calculated gas phase N—O bond lengths in the hydroxylamines, aldoximes, ketoximes and hydroxamic adds in Table 2. The horizontal axis is the same in each case... 

TABLE 8. Computational determination of acid site and conformation of hydroxamic adds... 

At about the same time, hydroxamic adds and oximes were found to react directly with organophosphorus compounds.85 2-PAM I was found to react In vitro with sarin with marked deviation from first-order kinetics that suggested that the reaction actually consists of (at least) two sequential reactions. Green showed that quatemlzed pyridine aldoximes react with an organophosphorus (OP) compound In three steps ... 

The known complexes, MIVL4 (Table 43), precipitate from aqueous solutions of actinide(IV) compounds on addition of the ligand. Somewhat surprisingly, one hydroxamic add, (PhCO)NHOH, behaves as a neutral ligand, and the complex Th(N03)4-2(PhC0)NH0H... 

The complexing capacity of hydroxamic acids was predicted by Werner in 1908, who also indicated the metals most likely to form stable complexes.288 Since then, the formation of poorly soluble and intensely coloured hydroxamates has been used for analytical determinations for a number of metal ions, such as Fe3+, Mos+, Vs+ etc. A recent general review of transition metal complexes of hydroxamic adds included the few known examples of silver(I) complexes.289... 

The preference of hydroxamic acids to form metal complexes through the hydroxamide functional group (1) and not through the hydroxyoxime structure (2) is confirmed by IR,27,28 UV,29 ESR30 and NMR28 spectral studies. Hydroxamic adds bind metal ions to form complexes with structure (3) rather than structure (4), for which evidence has been claimed31 in one case only. 

Pal and Kapoor74 have studied the reactions of isopropoxides of aluminum, titanium and zirconium with benzo- and phenylaceto-hydroxamic adds in anhydrous benzene. Solid products of the types Al(OPr )3 L and M(OPri)4 L (where M = Ti or Zr and L is the hydroxamic acid) have been isolated all the aluminum and zirconium products are white in colour whereas titanium ones are yellow. The mixed isopropoxide hydroxamates interchange their isopropoxy group with r-but-oxy groups, yielding r-butoxide products. 

Valinomycin metal complexes, 969 Vanadium complexes acetylacetone exchange reactions, 380 1,4-diaza-l,3-butadiene, 209 dioxygen mononuclear, 321 hydrazido(2-), 148 hydroxamic adds, 506 phthalocyanines, 865 polypyrazolylborates, 248 porphyrins, 824 dioxygen adducts, 325... 

Peptide a-oxo acids, a-oxo esters, and a-oxoamides are also potent inhibitors of cysteine and serine proteases. Oxidation of peptide a-substituted carboxylic acid derivatives provides a general route to these compounds (Section 15.1.5). Peptide hydroxamic acids have been shown to be inhibitors of metalloproteinase and some have been reported to have antibiotic, anticarcinogenic, and antiviral activities. Peptide hydroxamic adds may be prepared by solution and solid-phase methods using a variety of resins (Section 15.1.6). a-Aminoboronic acids may be prepared by several routes and are reported to be inhibitors of aminopepti-dases. Procedures have been developed for their incorporation into peptides (Section 15.1.7). 

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