Glycine hydroxamic acid

Palamidessi and Bernardi have obtained 2-chloropyrazine 1-oxide by mild treatment of pyrazine 1,4-dioxide with phosphoryl chloride. The structure of the 1-oxide was confirmed by hydrolysis to 2-hydroxy-pyrazine 1-oxide, which was also prepared by direct synthesis from glyoxal and glycine hydroxamic acid.398 This synthesis is illustrative of a general method for preparing 2-hydroxypyrazine 1-oxides by condensation of a,/3-dicarbonyl compounds with a-aminohydroxamic acids. An analogous synthesis of 2-aminopyrazine 1-oxides has already... 

Glycine hydroxamic acid Glyoxal 2-Hydroxy 547a... 

Diamino-l,8-dihydroxyanthraquinone (diaminochrysaz in) Aminoacethydroxamic acid (glycine hydroxamic acid)... 

As second example for the scale-up of solid-phase reactions directly on solid support, we chose an arylsulfonamido-substituted hydroxamic acid derivative stemming from the matrix metalloproteinase inhibitor library (MMP) of our research colleagues (Breitenstein et al. 2001). In this case, there was already a solution-phase synthesis available for comparison (see Scheme 4). The synthesis starts with the inline formation of a benzaldehyde 18 with the glycine methyl ester, which is then reduced to the benzylamine 20 using sodium borohydride in methanol/ THF (2 1). The sulfonamide formation is carried out in dioxane/H20 (2 1) with triethylamine as the base and after neutralisation and evaporation the product 21 can be crystallised from tert. butylmethyl ether. After deprotection with LiOH, the acid is activated by treatment with oxalyl chloride and finally converted into the hyroxamic acid 23 in 33.7% yield overall. 

Unlike certain cycle hydroxamic acids, hadacidin may arise biosyntheti-cally by oxidation at the amino rather than the amide stage. N-hydroxy-glycine, but not the N-formyl derivative of glycine, is a precursor of the molecule in P. aurantia-violaceum (128). 

Cyclic hydroxamic acids are formed by partial reduction of A -(nitrophenyl)gly-cine in an acidic medium at 60 C. The glycine ester (72.6) may be heated with a base to give the dione. 

Measuring Transglutaminase Activity. Enzymic activity of transglutaminase is measured by the hydroxamate procedure with N-carbobenzoxy-L-glutaminyl-glycine (Z-Gln-Gly) (Fig. 2). The enzymic activity unit is defined as the amount causing the formation of 1 /tmole of hydroxamic acid in one minute at 37°C (7). 

Amino acids Amines, methylated amino acids, betaines, cyanogenic glycosides, mustard oils, alkaloids, glycine conjugates, glutamine and ornithine, 5-alkylcysteine derivatives, di-oxopiperazines, peptides (penicillins), hydroxamic acids. 

Many investigators have studied the incorporation of labeled amino acids into proteins. The system involved in mammalian cells seems to be associated with microsomes, but requires factors from the soluble portion of the cell. Both ATP and GTP are required. The function of the ATP may be to form activated amino acids. Several systems have been found with relative specificity for various amino acids that catalyze the exchange of pyrophosphate with ATP in the presence of the amino acid, and presumably form adenyl-amino acid compounds. The activated amino acids react with hydroxylamine to form hydroxamic acids. Several reactions have been considered as models for peptide bond formation. These include the formation of hippuric acid, in which benzoyl CoA condenses with glycine in a reaction similar to the acetylation of... 

If GSH is incubated with hydroxylamine, a hydroxamic acid is enzymatically formed. As is shown in Table IV, this reaction also requires ADP and arsenate. This hydroxamic acid so far has not been identified. However, if the analogy with the glutamine system holds, the reaction should involve the replacement of the glycine of GSH by hydroxylamine. 

In 1998, Dankwardt used for the first time ester linkers for the synthesis of hydroxamates [116]. The synthesis of hydroxamates and hydroxamic acids is a known synthesis on solid supports but former approaches used special hydroxamate linkers that had to be synthesized in previous reactions. The methodology published by Dankwardt is very simple because ArgoGel-OH resins can be used without further derivatization to bind protected amino acids 88 in the presence of coupling reagents. Hydroxamic acids 90 were cleaved by the addition of hydroxylamine in 21% (sterically hindered amino acids) to quantitative yields (glycin. Scheme 12). 

In addition to glycine, the N-hydroxyamino acid analogs of alanine, tyrosine, lysine (e-NOH), ornithine (d-NOH), leucine and isoleucine have all been found in nature in the form of hydroxamic acids (Keller-Schierlein et aL, 1964). The... 

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