达泊西汀是第一个被批准用于治疗早泄的口服药,氟西汀是临床应用最广泛的治疗抑郁症药物之一，托莫西汀是用于治疗所有年龄段注意力缺陷性多动症的第一个非兴奋性药物。这三个药物都是选择性5-羟色胺再摄取抑制剂（SSRI）类药物，具有“1,3-二杂原子”共同结构单元。. 本项目研究这三个药物的合成方法，探索和解决其中的基本科学问题。首先以杂Michael加成/还原串联反应为研究对象，拟通过以有机不对称催化Aza-Michael加成/还原串联反应为关键步骤合成达泊西汀；拟通过以Oxy-Michael加成/还原串联反应为关键步骤，实现氟西汀和托莫西汀的合成。同时，探讨不同反应条件对选择性的影响规律，为构筑手性“1,3-二杂原子”结构单元提供试验和理论基础。本项目的研究体系新颖，为上述SSRI药物的合成提供了一种简洁、高效的合成方法，具有十分广阔的研究和应用前景。

Dapoxetine is the first approved oral medicine for the treatment of premature ejaculation; Fluoxetine is the most widely used clinical treatment of depression drug; Atomoxetine is the first non-excitatory drug for the treatment of all ages with attention deficit hyperactivity disorder. These drugs containing common “1, 3-diheteroatom” unit are all selective 5–HT reuptake inhibitors (SSRI).. This project focuses the synthesis of these drugs, explores and solves basic scientific problems. First，we study the hetro-michael/ reduction tandem reaction. Dapoxetine will be synthesed by organocatalytic asymmetric aza-Michael/ reduction tandem reaction as the key step. Fluoxetine and Atomoxetine will be synthesed by oxy -Michael/ reduction tandem reaction as the key step. At the same time, the different reaction conditions on the selectivity will be studied. This project will build experimental and theoretical basis for the synthesis of chiral“1, 3-diheteroatom” unit. The new system of this project will provide a concise and efficient synthetic methods for the synthesis of these SSRI drugs and have a very broad research and application prospects.