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.
This process increases the amount of RNA present in the cell and their respective encoded proteins. Synthesis of Trichostatin A Trichostatin A was the first naturally occurring HDI to be discovered. It causes an increase in acetylated histones in a variety of mammalian tumor cell line.
45 Trichostatin A was shown to be a selective histone deacetylase inhibitor, reversibly inhibiting classes I, II and IV types of HDAC while not affecting class III. 46 The first portion of the synthesis is shown in scheme 9.
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 second portion of the synthesis is presented in schemes 10. 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. Keywords: Keyword Histone deacetylase inhibitors, Matrix metalloproteinase inhibitors, HIV, Hydroxamaates, Ribonucleoside diphosphate reductase Cite this paper: David I. The reasonable way of producing hydroxamic acid derivative is the reaction of hydroxylamine with acid chlorides or esters. 13 Hydroxamic acids are capable of inhibiting a variety of enzymes, including ureases, 14, 15 peroxidises 16, and matrix metalloproteinases.