Divergent Total Synthesis of Denudatine Alkaloids Cochlearenine, Macrocentrine, Dictizine, 15‐Veratroyl‐17‐Acetyl‐19‐Oxodictizine, and the Proposed Structure of Acochlearine

The first asymmetric total syntheses of four denudatine alkaloids, cochlearenine, macrocentrine, dictizine, and 15‐veratroyl‐17‐acetyl‐19‐oxodictizine, along with the asymmetric synthesis of the proposed structure of acochlearine, were accomplished in a divergent manner. Highly fused tetracyclic skeletons (A/B/E/F rings) with different N ‐alkyl groups (Me and Et) were constructed by Brønsted acid promoted intramolecular Mannich reactions. The bicyclo[2.2.2]octane C/D rings were constructed via two‐fold intermolecular Diels–Alder reactions. By utilizing these key processes, the common intermediates, possessing the complex cage‐like hexacyclic skeleton, were constructed. From these common intermediates, the four denudatine alkaloids were synthesized through late‐stage, chemo‐ and stereoselective modifications around the A/C rings. The spectroscopic data of the proposed structure of acochlearine were inconsistent with those of natural acochlearine.