Total syntheses of the monoterpene indole alkaloids (±)-alstilobanine A and E and (±)-angustilodine.

ABSTRACT: 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 ?-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 ?-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.

SUBMITTER: Feng Y 

PROVIDER: S-EPMC3913098 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature