Hydroxamate s

Folkers J P, Gorman C B, Laibinis P E, Buchholz S and Whitesides G M 1995 Self-assembled monolayers of long-chain hydroxamic acids on the native oxides of metals Langmuir 813-24... 

In 2000, an efficient three-step procedure for the synthesis of 5-substituted 3-isoxazolols (without formation of undesired 5-isoxazolone byproduct) was published. The method uses an activated carboxylic acid derivative to acylate Meldrum s acid, which is treated with A,0-bis(ten-butoxycarbonyl)hydroxylamine to provide the N,0-di-Boc-protected P-keto hydroxamic acids 14. Cyclization to the corresponding 5-substituted 3-isoxazolols 15 occurs upon treatment with hydrochloric acid in 76-99% yield. 

Shaw and McDowellhave prepared imidazolone derivatives by cyclization of a-acylamino amides. In a variation of this reaction the azlactone (30) was gradually converted to the hydroxamic acid (31) by methanolic hydroxylamine. Sodium methoxide and hydroxylamine readily gave the acyclic hydroxamic acid (32) which could be cyclized to 31 by dilute acid. Benzyloxyurea has been used in the sjrnthesis of pyrimidine hydroxamic acids (33) by reaction with /S-diketones followed by catalytic hydrogenation of the benzyl group. Protection... 

The method which has been of most preparative value is that established by Panizzi el and Di Maio and Tardella. Benzene-sulfonhydroxamic acid (74), known as Piloty s acid, reacts with a cyclic ketone (73) in alkaline media at 0 , to produce the ring-expanded hydroxamic acids (75 and 76) in approximately equal yield. 

The reaction is based on an early observation by Angeli and Ahrens that Piloty s acid converted aldehydes to hydroxamic acids, and this has formed the basis of the Angeli-Rimini aldehyde test. Di Maio and Tardella propose the above reaction sequence, consistent with the observed second-order kinetics. The possibility that benzenesulfon-hydroxamic acid would decompose in alkali to give nitroxyl (HNO)... 

Alicyclic hydroxamic acids undergo several specific oxidative cleavage reactions which may be of diagnostic or preparative value. In the pyrrolidine series compounds of type 66 have been oxidized with sodium hypobromite or with periodates to give y-nitroso acids (113). Ozonolysis gives the corresponding y-nitro acids. The related cyclic aldonitrone.s are also oxidized by periodate to nitroso acids, presumably via the hydroxamic acids.This periodate fission was used in the complex degradation of J -nitrones derived from aconitine. 

The tenth volume of this serial publication comprises six chapters, four of which deal with the general chemistry of a specific group of heterocyclic compounds pyridopyrimidines (W. J. Irwin and D. G. VVibberley), benzofuroxans (A. J. Boulton and P. B. Ghosh), isoindoles (J. D. White and M. E. Mann), and pyrylium salts (A. T. Balaban, W. Schroth, and G. Fischer). The remaining chapters are concerned with indole Grignard reagents (R. A. Heacock and S. Kasparek) and with cyclic hydroxamic acids (J. B. Bapat, D. St. C. Black, and R. C. Brown).The international flavor of the publication is preserved our contributors come from six countries in three continents. 

Metal complexes of hydroxamic acid analogues. S. Mizukami and K. Nagato, Coord. Chem. Rev.,... 

Knobler Y, Bittner S, Frankel M (1964) Reaction of N-carboxy-alpha-amino-acid anhydrides with hydrochlorides of hydroxylamine O-alkylhydroxylamines + amines syntheses of amino-hydroxamic acids amido-oxy-peptides + alpha-amino-acid amides. J Chem Soc 3941... 

D. W. Fong and B. S. Shambatta. Hydroxamic acid containing polymers used as corrosion inhibitors. Patent CA 2074535,1993. 

Additional P2 proline-containing PDF inhibitors have been reported in the patent literature by Dainippon and Questcor [95, 96]. The Dainippon examples disclosed contain an A-formyl-A-hydroxylamine group and possess good antibacterial activity against S. aureus, S. pneumoniae, Streptococcus pyogenes. Enterococcus faecium and M. catarrhalis [95]. The Questcor patent application describes various proline-containing hydroxamic acid inhibitors [96]. 

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]. 

Researchers at Combio and Arpida have reported a series of isoxazole-3-hydroxamic acids as PDF inhibitors [109], Molecular modelling studies predict that the aryl substituent of isoxazole (37) binds into the SF pocket and that the oxygen atom of the isoxazole is involved in a H-bonding interaction with Ile-44 in E. coli PDF, similar to the PF carbonyl of actinonin. None of the inhibitors reported has sub-micromolar inhibitory activity against E. coli or S. aureus PDF. Not surprisingly, these moderately active inhibitors also lack antibacterial activity. 

Moy FJ, Chanda PK, Chen JM, Cosmi S, Edris W, Skotnicki JS, Wilhelm J, Powers P. NMR solution structure of the catalytic fragment of human fibroblast collagenase complexed with a sulfonamide derivative of a hydroxamic acid compound. Biochemistry 1999 38 7085-7096. 

Fomsgaard I S, Mortensen AG, Gents M B and Understrup AG (2004), Time-dependent transformation of varying concentration of the hydroxamic acid metabolites MBOA and BOA in soil , 2nd European Allelopathy Symposium, 3-5 June 2004, Poland, Pulawy, 61-63. 

Mogensen B B, Mathiassen S, Krongaard T, Eljarrat E, Villagrasa M, Guillamon M, Tabemer A and Barcelo D (2004), Quantification of hydroxamic acid allelochemicals in wheat varieties grown under varying conditions , 2nd European Allelopathy Symposium, Pulawy, Poland, 50-53. 

Metal alkoxides undergo alkoxide exchange with alcoholic compounds such as alcohols, hydro-xamic acids, and alkyl hydroperoxides. Alkyl hydroperoxides themselves do not epoxidize olefins. However, hydroperoxides coordinated to a metal ion are activated by coordination of the distal oxygen (O2) and undergo epoxidation (Scheme 1). When the olefin is an allylic alcohol, both hydroperoxide and olefin are coordinated to the metal ion and the epoxidation occurs swiftly in an intramolecular manner.22 Thus, the epoxidation of an allylic alcohol proceeds selectively in the presence of an isolated olefin.23,24 In this metal-mediated epoxidation of allylic alcohols, some alkoxide(s) (—OR) do not participate in the epoxidation. Therefore, if such bystander alkoxide(s) are replaced with optically active ones, the epoxidation is expected to be enantioselective. Indeed, Yamada et al.25 and Sharp less et al.26 independently reported the epoxidation of allylic alcohols using Mo02(acac)2 modified with V-methyl-ephedrine and VO (acac)2 modified with an optically active hydroxamic acid as the catalyst, respectively, albeit with modest enantioselectivity. 

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