Common Strategy for the Synthesis of Some Strychnos Indole Alkaloids

Indole alkaloids are important natural
compounds with interesting
bio-activities that can be found in various species belonging to the
Amaryllidaceae, Apocynaceae, or Strychnaceae families. Although these
compounds have different connections, substituents, and functionalities,
their main core can be produced via the formation
of a common functionalized tetracyclic subunit, which is rapidly obtained
by an oxidative de-aromatization process mediated by a hypervalent
iodine reagent from an inexpensive phenol containing a lactate moiety
as the chiral auxiliary. A subsequent stereoselective aza-Michael
addition and an intramolecular Heck-type reaction lead to the formation
of a common key intermediate. This approach provides a solid foundation
for the further elaborations of several natural products. The asymmetric
syntheses of (−)-strychnopivotine and the polycyclic main cores
of (−)-strychnosplendine, (+)-isosplendine, and (+)-malagashanol,
three other indole alkaloids, are reported.