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Synthesis of Benzohydroxamic Acid 3 The synthesis of compound 3 was achieved by reacting methyl benzoate 1 and hydroxylamine 2. Synthesis of Hydroxamates Using N, N1, NII–trimethoxy-N, NI, NII-trimethyl Phosphorus Triamides 5 Nui et al 31 reported the conversion of aromatic and aliphatic carboxylic acids, including sterically hindered substrates directly to hydroxamates using N, NI, NII-trimethoxy-N, NI, NII–trimethyl phosphorus triamide 5.

On condensation of aromatic or aliphatic carboxylic acid 4 0.01M and compound 5 0.005M in toluene at 60 for 0.5 to 1 h, the hydroxamate 6 was obtained in excellent yield. Ester Synthesis of Hydroxamate Riva et al 32 reported the transformation of methyl or ethyl carboxylic esters into the corresponding hydroxamic acid.

To achieve this, the ester 0.5 M in methanol and hydroxyl amine 10 eq was reacted in the presence of sodium methoxide 1 eq.

Following an optimization studies, they found that at 70 and 30 min, highest yield of the hydroxamate was obtained with high purity. Microware Activated Hydroxamic Acid Synthesis Massaro et al 33 has shown that the reaction of esters with hydroxylamine in the presence of a base under microwave activation provides hydroxamic acids in good yield and high purity.

Carbodiimides hydrolyze to form ureas, which makes them uncommon in nature. Hydroxyurea are also used for treatment of chronic myelogenal leukemia, myeloproliferative syndromes and sickle cell anemia. 2 Hydroxamates of amino acids are effective inhibitors of amino peptidases.

From the perspective of small molecule activation, carbodiimides are. Hydroxamates such as fosmidomycin and desferrioxamine B are potent antimalarial agent. Ugwuja, Synthesis and Biological Applications of Hydroxamates, American Journal of Organic Chemistry, Vol. 3 Their mode of action results from the formation of bidentate ligand with active site of zinc.

HDAC performs the reverse process of histone acetyl co A to the lysines on the histone, inducing a state known as hyper acetylation.

The broad biological activities of hydroxamates and the need to improve on their synthetic routes informed the review of their synthesis and biological applications. 5, 6 A number of synthetic routes are available for the preparation of hydroxamic acids, 7-12 but some are tedious, time consuming and costly as well. Colombo, An improved synthesis of the HDAC inhibitorn trichostatin A, Master s Theses and Doctoral Dissertations, Eastern Michigan University, 2009, 1-2.

The reaction of carboxylic acid 1eq and 2-chloro-4,6-dimethoxy-1,3,5-triazine 1.2 eq in the presence of N-methyl morpholine 3 eq., THF at room temperature for 1-3 h gave the 4,6-dimethoxy-1,3,5-triazine intermediate 20, compound 20 upon treatment with substituted hydroxylamine 1 eq at room temperature for 8 h gave the target product 21.

There are many more general synthetic routes that have been reported and cannot be described for lack of space but are mentioned in this review.

desferrioxamine B, fosmidomycin, siderophores 28 and allergic diseases.

29 The wide biological application of hydroxamates necessitates the review of its synthesis and biological applications. General Synthesis of Weinreb Amides Hydroxamic acids are prepared usually from esters or acid chlorides or carboxylic acids.2.1.

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