Gram‐Scale Total Synthesis of Sarpagine Alkaloids and Non‐Natural Derivatives

This work describes the total synthesis of three members of the sarpagine alkaloid family and ten non‐natural congeners through an improved synthetic sequence, which was designed for gram‐scale production of materials suited for structure–activity relationship (SAR) studies. Furthermore, the manuscript details how the synthetic route was used to access the biogenetically completely unrelated Stemona alkaloid parvineostemonine (34), providing a showcase for efficient synthetic design. A generalized total synthesis for Stemona and sarpagine alkaloids was achieved (see graphic). The common privileged intermediate was accessed via a [5+2]‐cycloaddition reaction in six steps. Both alkaloid families were synthesized in a total of 11 and 12 steps, respectively, of which they shared six steps in total.