N-hydroxy group

N-Amino and N-nitro groups N-Hydroxy groups and N-oxides N-Hatogeno groups... 

N-Hydroxy arylamines readily form glucuronide conjugates, but in contrast to the N-hydroxy arylamides, these are N-glucuronides which are unreactive and stable at neutral pH. The N-glucuronides are readily transported to the lumens of the urinary bladder and intestine where they can be hydrolyzed to the free N-hydroxy arylamines by mildly acidic urine or by intestinal bacterial 3-glucuronidases (13,14). Non-enzymatic activation of N-hydroxy arylamines can occur in an acidic environment by protonation (15,16) of the N-hydroxy group (VIII) as well as by air oxidation (reviewed in 17) to a nitrosoarene (IX). 

The importance of protonated N-hydroxy arylamines as ultimate carcinogens has been suggested for some time (28,40,139). From studies on their reactivity with nucleic acids at different pH s (2,15,16,63,130,131), the pK for protonation of the N-hydroxy group appears to be between pH 5a and 6 thus, a significant proportion (1-10%) of the N-hydroxy derivative exists as the protonated form even under neutral conditions. This would account for the significant levels of covalent modification of DNA observed in vitro by reaction with N-hydroxy arylamines at neutral pH. Consequently, it has been proposed that in vivo formation of non-acetylated aryl... 

N-Hydroxyindols (11) have been prepared in two ways,65 [Eqs. (24) and (25)]. Equation (25) is a variation in which the hydroxylamino group is oxidized to a nitroso group, which then adds to a C=C bond. In acidic solution the N-hydroxy group can be reductively removed. 

Irradiation of the steroidal nitroxide (56) in toluene solution afforded 39% of (57) and 57% of the unstable iV-hydroxy-derivative (58). This shows the N-hydroxy-group to be a potential tool for remote functionalization in appropriate molecules. These results, along with similar ones obtained in other series,... 

N -Hydroxy groups can be acetylated (AC2O) and O-alkylated in basic media by methyl iodide. 1-Hydroxypyrazole 2-oxides are quite strong acids. 

N-Hydroxy peptides, peptides with N -hydroxy moieties. The hydroxamate groups in such pseudopeptides may act as metal coordination sites in order to preorganize peptide structures. The N -hydroxy group confers different hydrogen bonding capabilities compared to native peptides, thus modifying the conformation and potentially also molecular recognition [J. Lawrence et al., Org. Biomol. Chem. 2006, 4, 3125]. 

Zileuton reportedly undergoes stereoselective glucuronidation at a N-hydroxy group. Sweeny et al. [131] showed that the human microsomal glucuronidation rates for the S enantiomer were 3.6 to 4.3 times greater than for antipode. The consequence of stereoselective metabolism is apparent in vivo with 49 to 76% faster clearance of S-zileuton after single oral doses of 200 to 800 mg in normal healthy subjects [130]. Furthermore, it has been demonstrated that each enantiomer of zileuton competitively inhibits the phase II metabolism of respective antipode [131]. 

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