非对映选择性合成他达那非

Diastereoselective Synthesis of Tadalafil

以D-色氨酸为起始原料经酯化、Pictect-Spengler反应、酰化和氨解-环合四步制备新的磷酸二酯酶5抑制剂他达那非,总收率为66.8%。在Pictect-Spengler反应中采用非对映控制方法高选择性地合成cis-β-咔啉关键中间体,避免了trans-异构体的分离。

Tadalafil, a new phosphodiesterase （V） inhibitor, was prepared from D-tryptophan as the starting material via a four-step process of esterification, Pictect-Spengler reaction, acylation and aminolysis-cyclization with an overall yield of 66.8 %. A diastereocontrol method was used to highly-selectively synthesize the key intermediate cis-β-carboline in the Pictect-Spengler reaction to avoid the separation of the trans-isomer.