Aspidosperma alkaloids Mannich reactions

The tandem Michad-Mannich reactions serve to assemble a tetracyclic intermediate with the aspidosperma alkaloid skeleton from 3-indoleacetyl chloride in one step [138]. 

Perhaps the best illustration of the utility of tandem aza-Cope reairangement-Mannich cyclization reactions for assembling complex molecular skeletons is found in the total synthesis of the Aspidosperma alkaloid ( )-16-methoxytabersonine (Scheme 56). The crucial step in this synthesis was the high-yielding conversion of aniline (156) to 16-methoxy-l,2,6,7-tetradehydroaspidospermidine (157), a trans-... 

The enamine (/dienamine)-iminium cycle-specific cascade catalysis is an important constituent of amine-catalyzed cascade reactions [10]. This strategy has been explored extensively and also applied to natural product synthesis. One such example is the total synthesis of dihydrocorynantheol, which was first isolated from the bark of Aspidosperma marcgravianum in 1967 [29]. This indole alkaloid is a member of the corynantheine and was found to exhibit antiparasitic, antiviral, or analgetic activities, which have attracted considerable attention from the synthetic community. Among those reported total syntheses, Itoh et al. developed a Mannich-Michael cascade reaction catalyzed by L-proline 52 for the total synthesis of ent-dihydrocorynantheol 54 (Scheme 3.8) [30], The cascade reaction of 3-ethyl-3-buten-2-one 51 with dihydro-P-carboline 50 catalyzed by 30mol% of (S)-proline afforded the tetracyclic core structure 53 in 85% yield. Excellent stereoselectivity was achieved in this cascade reaction (99% enantiomeric excess and almost complete diastereomeric control). Therefore, this organocascade reaction could lead expeditiously to construction of the core structure, which enabled the authors to accomplish the total synthesis of enl-dihydrocorynantheol 54 in just five steps. 

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