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 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.
This silencing can become permanent if the unprotected lysines are then methylated.
HDAC performs the reverse process of histone acetyl co A to the lysines on the histone, inducing a state known as hyper acetylation.
The ester 23 on reduction with Li BH4 gave the alcohol.
Oxidation of alcohol 24 under Swern condition 47 gave aldehyde 25 which was treated with an aryl Grignard reagent to produce alcohol 26.