Pyrrole Strategy for the γ-Lactam-Containing Stemona Alkaloids: (±)Stemoamide, (±)Tuberostemoamide, and (±)Sessilifoliamide A

Stemona alkaloids contain family members with diverse structural scaffolds. Many of them feature a gamma-lactam ring embedded in their characteristic 5-7-5 fused tricyclic core. Herein a pyrrole strategy was developed to enable the total syntheses of three Stemona alkaloids: (+/-)stemoamide, (+/-)tuberostemoamide, and (+/-)sessilifoliamide A. In these cases, a substituted pyrrole was used as the gamma-lactam precursor. A sequential pyrrole oxidation and enamide reduction were realized to convert the pyrrole to the corresponding gamma-lactam in those three natural products. The use of a pyrrole in an early stage of the synthesis offers the advantage of rapid construction of the key intermediates by exploiting its nucleophilicity.