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. 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 TBS group was later recovered with tetra- normal-butylammonium fluoride TBAF in THF to give alcohol 28 in 91 yields. The second portion of the synthesis is presented in schemes 10. 17, 18 These class of compounds are used in the design of therapeutics targeting cancer 19, 20 e.g.
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. 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. Ugwu, Department of Pure and Industrial Chemistry, University of Nigeria, Nsukka, Nigeria. Abstract Hydroxamates are physiologically active compounds. They have found applications as histone deacetylase inhibitors widely applied in cancer treatment such as vorinostat, belinostat, panobinostat and trichostatin A. They are amides where the hydrogen H atom of NH center has been replaced by an OH. Hydroxamates are deprotonated product of hydroxamic acid and acts as excellent ligand. Ugwuja3 1Department of Pure and Industrial Chemistry, University of Nigeria, Nsukka, Nigeria 2National Centre for Energy Research and Development, University of Nigeria, Nsukka, Nigeria 3Department of Chemical Sciences, Federal University, Wukari, Nigeria Correspondence to: David I. Introduction Hydroxamates are class of organic compounds bearing the functional group RICON OH RII as organic residues and CO as a carbonyl group. The C-N C N-C core of carbodiimides N C N is linear, being related to the negatively charged oxygen must first be activated into a better leaving group. Cipemastat, marimastat, periostat, ilomastat and batimastat are all hydroxamate-based inhibitors of matrix metalloproteinase and are by so used in management of cardiovascular diseases. Hydroxamic acids have been the source of much biochemical interest in recent years reflecting the fact that they demonstrate a wide variety of biological activities. Email: Copyright 2014 Scientific Academic Publishing. There are hydroxamates with reported anti-HIV activity such as the hydroxyurea which acts as inhibitors of cellular enzyme ribonucleoside diphosphate reductase. 1 Hydroxamates have high affinity for ferric ions that nature has evolved families of hydroxamic acids to function as no N-binding compounds siderophores in bacteria. 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. 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.