Total Synthesis of Bioactive Alkaloid Natural Products Starting with 3,5-Dibromo-2-pyrone as Key Synthon

Abstract

The Diels-Alder cycloaddition products of 3,5-dibromo-2-pyone with various dienophlies were successfully utilized for the total syntheses of amaryllidaceae alkaloids; pancratistatin, α-lycorane, 1-deoxylycorine and lycorine. For the synthesis of pancratistatin, β-silyl styrene was elaborated and used as dienophile in the Diels-Alder reaction. The silyl group in the corresponding cycloadduct was manipulated into the pivotal C1-hydroxyl group via the process involving a Peterson elimination and epoxidation. To synthesize α-lycorane and 1-deoxylycorine, we used an Eschenmoser-Claisen rearrangement as key reaction for the construction of D ring that led to the rapid synthesis of α-lycorane. Further manipulation including facial-selective dihydroxylation and Chugaev elimination allowed us to accomplish the total synthesis of 1-deoxylycorine. Recently, we have also elaborated a new synthetic route to lycorine by using (E)-β-borylstyrene as a dienophile for the Diels-Alder reaction with 3,5-dibromo-2-pyrone. The boronate group in the cycloadduct was readily oxidized into the C-1 hydroxyl group of the lycorine.