N- hydroxylamine

Recently, one of the evolved MAO-N variants has been shown to catalyze the enantioselective oxidation of O-methyl-N-hydroxylamines (e.g. 16) yielding the corresponding -oxime (17) and recovered (R)-hydroxylamine (16) in enantiomeri-cally pure form (Figure 5.11) [21]. 

NMR has been used in conjunction with NMR in studies on reactions of [ N] hydroxylamine with fulvic and humic substances (Thom et al. 1992). 

Pseudopeptidic Hydroxamic Acids and N-formyl-N-hydroxylamines Non-peptidic Templates... 

More recently, screening efforts at Novartis have identified a hydroxamic acid containing a benzothiazinone ring system (32) [108]. This inhibitor is very potent versus S. aureus Ni -PDF (<5nM) and displays good selectivity versus matrix metalloprotease-2 (MMP-2) and MMP-13. Unfortunately (32), and all other analogues prepared, such as carbon isosteres (33), sulfones (34), N-substituted analogues (35) and N-formyl-N-hydroxylamines (36), lacked appreciable antibacterial activity in spite of their potent enzyme inhibitory activity. Further studies performed by Novartis suggest that these molecules are unable to penetrate the outer cell membrane of E. coli, and may bind to the cell membrane of S. aureus [108]. 

Transformation of chiral nitrones into enantiomer enriched a-chiral N -hydroxylamines and their derivatives, has been successfully employed in the enantioselective synthesis of (+ )-(R)- and (—)-(S)-zileuton (216). An expeditious synthesis of thymine polyoxin C (347), based on the stereocontrolled addition of 2-lithiofuran (a masked carboxylate group) to the A-benzyl nitrone derived from methyl 2,3-O-isopropylidene-dialdo-D-ribofuranoside, is described (Scheme 2.151) (194). 

The reaction of nitrones with indoles in the presence of HC1 gives indolyl N-hydroxylamines. In the presence of Me SiCl symmetrical diindolylalkanes are formed (Scheme 2.193) (679, 680). 

Many N-hydroxylamine derivatives are known. They appear to be non-explosive, stable compounds eg CH,HNOH (Ref 1) or HOOCCH2-NHOH (Ref 2)... 

Nitro-Derivatives of Aryl-N-hydroxylamine 6-Nitro-2,4-Dihydroxy lamino-phloroglucinol (called -phloroglucin in Ger). (H0)3C6(N02) (NHOH)2 mw 233.14, N 18.03%, OB -58.5% yellowish needles, mp 166° (decomp) has similar props and same meth of prep as the dinitro derivative described below... 

Di(f-butyl) tartrate has been used as an auxiliary to give asymmetric addition of alkynylzincs to nitrones, yielding optically active a-substituted propargylic N-hydroxylamines.43 Addition of product-like iV-hydroxylamine boosted ees up to 95%. 

To a solution of one drop (30 mg) of the unknown in 0.5 mL of 0.5 N hydroxylamine hydrochloride in ethanol add two drops of 20% sodium hydroxide solution. Heat the solution to boiling, cool slightly, and add 1 mL of 1 N hydrochloric acid. If cloudiness develops add up to 1 mL of ethanol. Add 10% iron(III) chloride solution dropwise with thorough mixing. A red-blue color is a positive test. Compare your unknown with a known ester. 

Gallagher, B. M., Pearson, W. H. Thermal cyclization of N-hydroxylamines with alkenes the reverse Cope elimination. Chemtracts Org. Chem. 1996, 9, 126-130. 

In the synthesis of hydroxamic acid 19a, having a free quaternary amino group (see Scheme 4.4), the intermediate sulfone 21 was synthesized by Pd-catalyzed reaction of phenol with p-bromo derivative 20 [24], Lithiation of 20, followed by nucleophilic addition to the A-Cbz imine of trifluoropyruvate 22 [25] afforded the a-CF3 a-amino acid derivative 23 in fair yields. Basic hydrolysis of the ester function gave the carboxylic acid 24, which was submitted to condensation with ()-15 n-hydroxylamine, affording hydroxamate 25. The subsequent hydrogenolysis of 25 afforded the target molecule 19a. 

Interestingly, this D5 variant is also able to catalyze the enantioselective oxidation of racemic O methyl N hydroxylamines 70 yielding the unreacted (H) substrate (ee = 99%) and the E oxime 71 product (Figure 14.37) [50]. 

Aminobiphenyl isomer Carcinogenicity Mutagenicity of parent compound Mutagenicity of N -hydroxylamine Planarity index (area/depth )... 

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