Total Synthesis of Naturally Occurring Amaryllidaceae Alkaloids, (−)-Elwesine and (−)-epi-Crinine

Catalytic asymmetric total synthesis of the naturally occurring Amaryllidaceae alkaloids, (-)-elwesine (2), (-)-dihydrooxocrinine (5), and (-)-epi-crinine (3) bearing the characteristic 5,10b-ethanophenanthridine framework has been reported. The synthesis features a key CBS reduction to generate an enantioenriched allylic alcohol (97% ee), followed by an orthoester Johnson-Claisen [3,3]-sigmatropic rearrangement to construct a sterically demanding all-carbon quaternary center at the pseudobenzylic position. Subsequent allylic oxidation furnishes the corresponding enone intermediate 7. Furthermore, a strategic sequence comprising ester aminolysis, aza-Michael addition, and a Pictet-Spengler cyclization efficiently constructed the 5,10b-ethanophenanthridine scaffold of these Amaryllidaceae alkaloids.