An improved asymmetric synthetic route to a novel triple uptake inhibitor antidepressant (2 S,4 R,5 R)-2-benzhydryl-5-((4-methoxybenzyl)amino)tetrahydro-2 H-pyran-4-ol (D-142)

Abstract

Triple monoamine reuptake inhibitors have been implicated in the development of a new generation of antidepressants with higher efficacy than the currently existing therapies. In this paper, we have developed an alternative efficient synthetic route for triple monoamine reuptake inhibitor D-142 in 18.5% overall yield in 11 steps starting from diphenylmethane. D-142 was developed by us recently. The key step of the present synthetic strategy is the preferential formation of a bromohydrin from olefin via a cis-bromonium intermediate, which introduced significant efficiency in the overall synthesis. Furthermore, we have developed an efficient way to recycle the optically active intermediate diol back to the desired chiral epoxide.