Asymmetric Total Synthesis of Senepodine F

The first asymmetric total synthesis of the Lycopodium alkaloid senepodine F, which contains a decahydroquinoline ring (AB-ring) and a quinolizidine ring (CD-ring) connected by a methylene tether, has been achieved. The key steps of this synthesis include an organocatalytic asymmetric Diels-Alder reaction, a diastereoselective intramolecular aza-Michael reaction, and an intramolecular SN2 cyclization to construct multisubstituted nitrogen-containing heterocycles. In addition, our total synthesis led to the stereochemical reassignment on the decahydroquinoline ring of senepodine F.

Automated summary

The first asymmetric total synthesis of the Lycopodium alkaloid senepodine F, containing a decahydroquinoline ring (AB-ring) and a quinolizidine ring (CD-ring) connected by a methylene tether, has been achieved. The key steps of this synthesis involve an organocatalytic asymmetric Diels-Alder reaction, a diastereoselective intramolecular aza-Michael reaction, and an intramolecular SN2 cyclization to construct nitrogen-containing heterocycles. Furthermore, this total synthesis allowed for the reassignment of the stereochemistry of the decahydroquinoline ring in senepodine F.