Flexible synthetic approaches to monoterpene indole alkaloids

Abstract

Preliminary model studies have demonstrated that our novel synthetic approaches to the Iboga- and seco-Yohimbine alkaloid families represent viable concepts for flexible strategies towards these alkaloid classes. The key step in the iboga case consists of an intramolecular nitrone-olefin 1,3-dipolar cycloaddition reaction of a monocyclic intermediate to yield a tricyclic isoxazolidine derivative that contains all of the stereochemical information of the envisaged final targets. The novel approach to seco-yohimbines involves a Cope-rearrangement of an appropriately functionalized azacyclodeca-3,7-diene precursor to establish ring D of the alkaloid target. Mild thermal treatment of an (E,E)-model compound gave the expected trans-3,4-divinylpiperidine derivative in 83% yield as the only detectable representative out of four possible diastereoisomers. In the context of an envisaged biomimetic synthesis of the hexacyclic Aristotelia alkaloid aristone, the feasibility of thermally induced oxy-ene and of anionic oxy-ene reactions was investigated employing a variety of model compounds. As it turned out, such transformations can be performed under various reaction conditions in mostly good yields and with excellent diastereoselectivity.