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White et al 38 reported the synthesis of hydroxamates using Deoxo-fluor; Katritzky et al 39 reported the synthesis of N-alkyl, O-alkyl and O, N-dialkyl hydroxamic acids via acyl benzotriazole intermediates; Gissot et al 40 reported high yielding one step synthesis of hydoxamates from various un-activated esters including enolizable esters and chrial α-amino acid esters and peptides ; Woo et al 41 reported the conversion of sterically hindered carboxylic acids to N-methoxy-N-methyl amides using 1.1eq of methanesulphonyl chloride; Martinelli et al 42 reported the palladium catalysed amino carbonylation of anyl bromides into the corresponding Weinreb amides; Nemoto et al 43 also reported a one pot synthesis of α-siloxy weinreb amides from aldelydes using N, O-dimethly amine and a masked acyl cyamide reagent bearing a tert-butyl dimethyl silyl group. Synthesis of Anticancer Hydroxamates Most hydroxamates used in cancer chemotherapy acts as histone deacetylase HDAC inhibitors. Histone deacetylase are a group of enzymes that removes acetyl groups from the lysine residues on a histone. HDAC performs the reverse process of histone acetyl co A to the lysines on the histone, inducing a state known as hyper acetylation. Hyper acetylation causes a decreased binding of the histones to DNA and leads to chromatin expansion, allowing transcription to take place. Protection of the commercially available hydro ester 22 with tertiary-butyldimethylsilyl chloride TBDMS-Cl gave silyl ester 23. The ester 23 on reduction with Li BH4 gave the alcohol.
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 method has been success fully applied to enantiomerically pure esters without loss of stereochemical integrity. 1-Propanephosphonic Acid Cyclic Anhydride T3P Promoted Synthesis of Hydroxamic Acid1-Propanephosphonic acid cyclic anhydride T3P promotes the synthesis of hydroxamic acids from carboxylic acids.
34 Application of ultra-sonication was showed to accelerate this conversion.
17, 18 These class of compounds are used in the design of therapeutics targeting cancer 19, 20 e.g.
histone deacetylases HDACs inhibitors like vorinostat, belinostat, panobinostat and trichostatin A, 21 cardiovascular diseases 22 e.g. hydroxyurea, 24 Alzheimer s, 25 malaria 26, 27 e.g.