O-methyl hydroxamates

P,y-Diamino analogues 49 of statine are prepared stereoselectively starting from the O-methyl hydroxamate derivative of N-protected statine. The reaction sequence involves the formation of a p-lactam intermediate obtained by internal cyclization under Mitsunobu conditions.184 Alternatively, direct amination of either a p-oxo ester 31 followed by reduction of the resulting enamine 50, 85 or by reduction of the corresponding ,p-unsaturated ester, 88 gives an enantiomeric mixture of the corresponding unprotected p-amine, which is protected by a carbamate prior to chromatographic separation (Scheme 20). 

Scheme 19.41 C(sp )-H alkylation with boronic acids directed by O-methyl hydroxamic acids.

C(sp ]-H Alkylation with Boronic Acids Directed by O-Methyl Hydroxamic Acids... 

As a follow-up work, Yu et al. succeeded to develop O-methyl hydroxamic acids-directed P-C(sp )-H arylation with aryl boronic acids imder mild reaction conditions in 2008 (Scheme 1.6) [23]. Remarkably, they identified that air could be employed as a sustainable external oxidant to replace silver salts (Scheme 1.6b). Since the O-methyl hydroxamic acids are readily to undergo a series of organic transformations, this protocol provides a facile access to a class of bioactive target molecules. 

SCHEME 3.79 Metal-free amiulation reactions between O-methyl hydroxamates and internal aUcynes [83]. 

Benzoic acids are convenient entry points for this chemistry as they can be converted in a one-pot reaction into an O-methyl hydroxamates [81] This reaction has been developed using rhodium complexes as catalysts and O-methyl hydroxamates as the substrates along with an internal alkyne [81]... 

The gas-phase acidities of hydroxamic acid and its N- and O-methyl derivatives have been measured using FT ion cyclotron resonance (Table 15)160. The acidity order is the same as that found in DMSO although, in this solvent, the O-methylation of acetohydroxamic acid decreases the acidity by 1 pK unit and the IV-methylation by 3.6 pK units, respectively. 

Other useful dehydrating agents are dimethylaminosulfur trifluoride (DAST), methyl A -(triethylammoniosulfonyl)carbamate (Burgess salt), acetic anhydride, oxalyl chloride, and phosphorous oxychloride, each one in combination with triethylamine (89). Dehydration of O-sUylated hydroxamic acids using trifluoro-methanesulfonic anhydride and triethylamine under mild conditions also gave nitrile oxides, which in the presence of olefins led to the formation of 2-isoxazolines in moderate to good yields (90). In view of the less readily available starting materials, this method probably will be of limited use. 

S Additional information <9, 15, 17, 18, 21, 24, 30, 33, 35> (<18> activity is regulated by light [28] <30> D-aspartate, L-glutamate and -alanine are inactive as substitutes for L-aspartate in the forward reaction, in the reverse reaction ADP cannot be replaced by AMP, UDP, GDP or IDP [1] <17> aspartokinase III, o-isomers of the derivatives of aspartic acid, including D-aspartate cr-benzyl ester and o-aspartate /)-hydroxamate are not substrates regardless of whether the a- or the -carboxyl group is derivatized, L-cysteine sulfinate and 2-methyl-DL-aspartate are no substrates... 

APCI has become a popular ionization source for applications of coupled HPLC-MS. Figure 1.33 shows an example of an application of HPLC-APCI coupling [79]. It shows the analysis obtained from extracts of maize plants. Six compounds are identified by mass spectrometry. These compounds have been identified as glucoconjugated DIMBOA (2,4-dihydroxy-7-methoxy-l,4-benzoxazin-3-one) and similar molecules that differ by the number of methoxy groups in the benzene ring and/or by the N-O methylation of the hydroxamate function. This example clearly shows the influence of the analyte on the type of observed molecular species. Indeed, the presence of an acidic group in the compound from peak 1 allows mainly the detection of deprotonated molecular ions, whereas the compound from peak 4 does not contain an acid group and thus leads only to the formation of adduct ions. 

The reaction of oxalylfo sisatin with O-methyl hydroxylamine hydrochloride yields the hydroxamic acid, with no further cyclization to a quinazoline occuring to yield quinazolines... 

Cyclic hydroxamic acids and N-hydroxyimides are sufficiently acidic to be O-methylated with diazomethane, although caution is necessary because complex secondary reactions may occur. N-Hydroxyisatin (105) reacted with diazomethane in acetone to give117 the products of ring expansion and further methylation (131, R = H or CH3). The benzalphthalimidine system (132) could not be methylated satisfactorily with diazomethane, but the A-methoxy compound was readily obtained118 by alkylation with methyl iodide and potassium carbonate in acetone. In the pyridine series, 1-benzyl-oxy and l-allyloxy-2-pyridones were formed hy thermal isomerization119 of the corresponding 2-alkyloxypyridine A-oxides at 100°. 

Other alkylation processes include the O-methylation of oximes, A-oxides, hydroxylamines, and hydroxamic acids. The preparation of oxime ethers using dimethyl sulfate has proven an effective methodology for the construction of sidechains designed for new cephalosporin antibiotics. Treatment of a-oxime esters with dimethyl sulfate afforded the a-methoximino esters, which were subsequently hydrolyzed to the acid and used as sidechains via acylation chemistry (eq 8). ... 

Qui L, Kelso MJ, Hansen C, West ML, Fairlie DP, Parson PG (1999) Antitumor activity in vitro and in vivo of selective differentiating agents containing hydroxamate. Br J Cancer 80 1252—1258 Rea S, Eisenhaber F, O Carroll D, Strahl BD, Sun ZW, Schmid M, Opravil S, Mechtler K, Ponting CP, AlUs CD, Jenuwein T (2000) Regulation of chromatin structure by site-specific histone H3 methyl-... 

From Nocardia strains several closely related compounds (nocobactins, formo-bactin, amamistatins) were isolated that contain three typically Fe " binding sites, two hydroxamate units, and ahydroxyphenyloxazole stmcture (cf. Sect. 3.2 below). The C-terminus is A-hydroxy-cyc/o-Lys bound to a long chain 3-hydroxy fatty acid, whose hydroxy group is esterified by A -acyl-A -hydroxy-Lys, the a-amino group of which is bound to 2-o-hydroxyphenyl-5-methyl-oxazole-4-carboxylic acid (Table 4). For the amamistatins the configuration of the cyclic lysine was determined as L, the open one as d, and that of C-3 of the fatty acid as (S). The involvement in the iron metabolism was not investigated. 

Pratasine. The utilisation of the cyclic hydroxamic acid 230 as a late precursor of pratosine has also been described [62] (Scheme 38). The preparation of 230 was achieved in excellent yield by photocyclisation of the borate ester 231 itself obtained from hydroxamic acid 232. Aqueous hydrolysis of the cyclic borate furnished 230, which underwent a smooth Michael addition to methyl propiolate to form the O-vinyl ester 233. The latter, on thermolysis in wet dimethylsulfoxide provided, via a 3,3-sigmatropic rearrangement, pratosine (204, 17% yield) and methyl pratosine-4-carboxylate (234,35% yield). 

The lactim/lactam tautomerism of hydroxamic acids and their O-alkyl and O-acyl derivatives has also been studied [146], Hydroxamic acids exist in the solid state and in polar solvents as the lactam tautomer only, whereas in nonpolar solvents the hydroximic tautomer is also present. Further analogous solvent-dependent lactim/lactam equilibria have been observed for certain Schiff bases (prepared from anilines and 2(4)-hydroxybenzaldehyde [256] or 2-hydroxynaphthaldehyde [257]), for 3-hydroxypyrazole [258], and for 3-methyl-l-phenylpyrazolin-5-one [259]. 

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