A stereoselective synthesis of (S)-dapoxetine starting from trans- cinnamyl alcohol
K. Venkatesana, b and K. V. Srinivasan*a
aDivision of Organic Chemistry, National Chemical Laboratory, Dr. Homi Bhabha Road, Pune- 411 008, India
bDepartment of Chemistry, McMaster University, Hamilton L8S4M1, Canada
E-mail:
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Abstract
A novel stereoselective synthesis of (S)-dapoxetine starting from commercially available trans- cinnamyl alcohol is described. Sharpless Asymmetric Epoxidation (SAE) is utilized as the key step in this synthetic strategy.
Keywords: Sharpless asymmetric epoxidation, (S)-dapoxetine, antidepressant, stereoselective synthesis
Introduction
Recently, it has been suggested that premature ejaculation (PE) might be associated with perturbations in serotonergic 5-hydroxytryptamine (5-HT) neurotransmission.1,2 It has been proposed that PE may be caused by decreased central serotonergic signaling, hyposensitivity of the 5-HT2C receptor, or hypersensitivity of the 5-HT1A receptor, all of which have been shown to decrease ejaculatory latency time in animal model systems.3,4 PE is a common problem, which may be associated with considerable anxiety, frustration, and negative impact on affected men and their sexual partners. No pharmaceutical agents have been approved for this indication. However, therapies that target 5-HT neurotransmission, such as selective serotonin reuptake inhibitor (SSRI) anti-depressants, have been used in this setting with varying efficacy and tolerability.
Dapoxetine is the first agent to be developed specifically to treat PE. This agent significantly prolongs IELT and increases the sense of control and sexual satisfaction for men with PE and their partners. Dapoxetine is well tolerated, with a favorable pharmacokinetic profile that allows for on-demand use. Dapoxetine hydrochloride is an SSRI with a short half-life developed specifically for the treatment of men with PE,5-8 but is slightly different from the SSRIs (such as
