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Oxidation of alcohol 24 under Swern condition 47 gave aldehyde 25 which was treated with an aryl Grignard reagent to produce alcohol 26. Alcohol 26 was treated with 2-methoxy propene and pyridinium p-toluenesulfonate PPTS to generate protected diol 27. 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. 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. Further, T3P has also been employed to activate the hydroxamtes leading to isocyanates via Lossen rearrangement 34. NHC–catalyzed Synthesis of Hydroxamic Acids N-Heterocyclic carbene NHC catalyzed amidation of a variety of aryl, alkyl, alkenyl and heterocyclic aldehydes with nitroso compounds is a powerful method for the synthesis of N-aryl hydroxamic acids in excellent yields. Chemoselective Esterificaiton Using Imidazole Carbamates Imidazole carbamates and ureas are used as chemoselective esterification and amidation reagents. A simple synthetic procedure allows the conversion of a wide variety of carboxylic acid to hydroxamates. Synthesis of Weinreb Amides Using Triazime Intermediates De Luca et al 37 reported the successful large scale synthesis of weinreb amide through a convenient and simple one-flask method via 2-chloro-4,6-dimethoxy-1,3,5-triazine intermediate 20.

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The ester 23 on reduction with Li BH4 gave the alcohol.

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.



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