GABAB agonists are known to exhibit muscle relaxant activity. Interest in these agonists as a useful lead for valuable new therapeutic agents has been rekindled due to reports of possible new applications especially in managing drug and alcohol tolerance. A novel fluorinated β-hydroxy ketone scaffold was developed in our lab to investigate new fluorinated analogues as GABAB agonists. Difluoromethyl halohydrins are important building blocks with potential applications in the pharmaceutical and agrochemical industries. Very few methods are reported for the synthesis of difluoromethyl halohydrins from alpha haloketones. Trifluorocetate release is a method that uses mild conditions to install a difluoromethyl into molecules. The difluoroenlate generated through the release of trifluoroacetate reacts with alpha haloketones to produce difluoromethyl halohydrins. The resultant fluorinated halohydrins can be used as intermediates in the synthesis of fluorinated tertiary alcohols, epoxides and oxazolidines. This method was used to synthesize derivatives of a novel difluoromethyl ketone scaffold which were evaluated as GABAB agonists using the inhibition of forskolin-stimulated accumulation of cAMP. Structure activity relationship studies of this novel scaffold were carried out.

Synthesis of α,α-difluoromethyl halohydrins and their application in the synthesis of γ-aminobutyric acid type B (GABAB) receptor agonists

255th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.