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.
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.
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.
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.
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.