USE OF AZA-COPE REARRANGEMENT MANNICH CYCLIZATION REACTIONS TO ACHIEVE A GENERAL ENTRY TO MELODINUS AND ASPIDOSPERMA ALKALOIDS - STEREOCONTROLLED TOTAL SYNTHESES OF (+/-)-DEOXOAPODINE, (+/-)-MELOSCINE, AND (+/-)-EPIMELOSCINE AND A FORMAL SYNTHESIS OF (+/-)-1-ACETYLASPIDOALBIDINE

The first total syntheses of the structurally unusual pentacyclic Melodinus alkaloids (+/-)-meloscine (1) and (+/-)-epimeloscine (2) and the hexacyclic Aspidosperma alkaloid (+/-)-deoxoapodine (4) are reported. The syntheses proceed via a highly functionalized common tetracyclic intermediate 7, which is accessed (with complete stereocontrol) by the title rearrangement of pyrindinol 10. These syntheses provide excellent examples of the power of tandem aza-Cope rearrangement-Mannich cyclization reactions as the key element of stereocontrolled alkaloid synthesis design.