Total Syntheses of the Monoterpene Indole Alkaloids (±)-Alstilobanine A and E and (±)-Angustilodine

A synthetic
strategy has been developed culminating in stereoselective
total syntheses of the small class of unusual monoterpenoid indole
alkaloids exemplified by alstilobanines A (3) and E (2) and angustilodine (1). A pivotal step includes
a novel intermolecular Michael-type addition of an indole ester dianion
to a piperidine-derived nitrosoalkene to form the C15, C16 bond of
the alkaloids. In addition, an application of the Romo protocol for
effecting a stereoselective intramolecular nucleophile-assisted aldol-lactonization
was employed, leading to a β-lactone incorporating the requisite cis-fused 2-azadecalin moiety and also setting the C15,
C19, C20 relative stereochemistry of the metabolites. It was then
possible to stereoselectively effect an aldolization of a dianion
derived from this indole ester β-lactone intermediate with formaldehyde
to introduce the requisite C16 hydroxymethyl group. Further manipulations
of the system ultimately led to the three alkaloids in racemic form.