Synthesis of enantiomerically pure milnacipran analogs and inhibition of dopamine, serotonin, and norepinephrine transporters

A series of Milnacipran analogs with variation in the aromatic moiety were prepared in high enantiomeric excess. Structure–activity relationships for two parallel enantiomeric series are described. The (−)-(1R,2S)-naphthyl analog (8h) showed the highest potency in the two series and is a triple reuptake inhibitor of the SERT, NET, and DAT.