Total Synthesis of Parvineostemonine by Structure Pattern Recognition: A Unified Approach to Stemona and Sarpagine Alkaloids

Through structure pattern recognition based total synthesis we designed a synthesis in which two biogenetically unrelated natural product families (Stemona‐ and Sarpagine alkaloids) share 50 % of their synthetic sequence. In this report, the efficiency of such a strategic approach is demonstrated in the total synthesis of the Stemona alkaloid parvineostemonine, proceeding through a privileged intermediate that we have previously transformed into biogenetically completely unrelated Sarpagine alkaloids. In addition, we capitalized on the symmetry properties of the privileged intermediate, which was obtained as two regioisomers. After their separation by column chromatography the two regioisomers were converted to the corresponding pair of enantiomers by one transformation. To the best of our knowledge, this feature (conversion of regioisomers to enantiomers) has never been applied to natural product synthesis, and proved to be very valuable, since it allowed to obtain both optical antipodes of parvineostemonine in a single synthetic campaign. This not only enabled the determination of the previously undisclosed absolute configuration of the natural product, but gave 60–200 mg amounts of both enantiomers of the natural product. The absolute configuration of the Stemona alkaloid parvineostemonine was elucidated by total synthesis. The synthetic strategy allows for a short and efficient access in eight steps from known building blocks and 12 steps from commercial starting materials. The synthetic route provides acceptable amounts of the natural product (70–200 mg). In the course of the synthesis both regioisomers produced in the [5+2]‐cycloaddition can be carried through due to the symmetry of the final product. These regioisomers are converted into the corresponding enantiomers by a Raney‐Nickel reduction, and thus deliver both optical antipodes of parvineostemonine in one synthetic campaign.