(S)-Duloxetine hydrochloride 1 is a medication used to treat major depressive disorder, generalized anxiety disorder, fibromyalgia and neuropathic pain (Figure 1). Due to its versatility in different treatments, many researchers have been attracted towards the development of different cost-effective synthetic routes. The drug contains a 3-aryloxy-3-aryl propylamine sub-unit in its basic structure. It acts as a dual inhibitor of serotonin and norepinephrine reuptake. A literature search reveals that most of the reported methods involve synthesis of enantiomerically pure alcohols as key chiral synthons, as presented in Scheme 1. In our research work, we have focused on the development of an efficient route for the synthesis of (S)-duloxetine hydrochloride 1 by modification of ketoamine intermediate a (Scheme 1), followed by enzymatic asymmetric reduction to obtain enantiomerically pure alcohol intermediate b (Scheme 1). To help with our planning, we did the retrosynthetic analysis shown in Scheme 2.
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