An efficient, high yield and one pot synthesis of phenyl cyclopropyl methanones on reaction of different aryl alcohols with 4'-fluoro-4-chloro-butyrophenone in THF/DMF in presence of NaH /TBAB is reported. All the compounds were evaluated for their antitubercular activities against M. tuberculosis H37 Rv in vitro displaying MICs ranging from 25-3.125 mcg/ml. The most active compounds showed activity against MDR strains and one of them showed marginal enhancement MST in mice. An increase in the global burden of tuberculosis with the worldwide mortality rate at 23% is major cause of concern in the socioeconomic and health sectors. 1,2 Tuberculosis in HIV infected and immuno-compromised individuals and the increasing trend of MDR TB poses a threatening challenge particularily in the developing world. 3 Although a number of lead molecules are in the pipeline of new drugs to combat the above challenge yet no new chemical entity has emerged in clinic for the last more than 40 years. 4,5 Hence there is an emergent need to develop new drugs, acting through a novel mechanism, in cost effective manner The incredible thickness mycobaterial cell wall being absent in human hosts owes a lot for the required long treatment of the disease and development of resistance against the known first line anti-TB drugs. 6-8 Therefore, it is a selective target and many crucial enzymes required in the biosynthesis of cell wall macromolecules and their inhibitors are being looked as future hope in the treatment of this disease. One of such enzyme system is FAS-II required in the initial steps of mycolic acid biosynthesis. 9 Many inhibitors of FAS-II are known and among them phenethyl alcohol 10 and Triclosan 10 are important for lead optimization. Further, during our work on this series of molecules antimycobacterial activity has been reported in simple acetophenones. 11 We also have identified a glycosylated phenyl cyclopropyl methanone (1) as very good antitubercular against MDR strains and in vivo too. 12
