Biogenetically inspired approach to the Strychnos alkaloids. Concise syntheses of (+/-)-akuammicine and (+/-)-strychnine

A linear synthesis of the indole alkaloid (+/-)-akuammicine (2) was complet ed by a novel sequence of reactions requiring only 10 steps from commercial ly available starting materials. The approach features a tandem vinylogous Mannich addition and an intramolecular hetero Diels-Alder reaction to rapid ly assemble the pentacyclic heteroychimboid derivative 8 from the readily a vailable hydrocarboline 6. Oxidation of the E ring of 8 gave the lactone 9 that was converted into deformylgeissoschizine (11). The subsequent elabora tion of 11 into 2 was effected by a biomimetically patterned transformation that involved sequential oxidation and base-induced skeletal reorganizatio n. A variation of these tactics was then applied to the synthesis of the C( 18) hydroxylated akuammicine derivative 36. Because 36 had previously been converted into strychnine (1) in four steps, its preparation constitutes a concise, formal synthesis of this complex alkaloid.