A divergent approach to the synthesis of the yohimbinoid alkaloids venenatine and alstovenine

Abstract

The yohimbinoid alkaloids continue to receive considerable attention from the synthetic community because of their interesting chemical structures and varied biological activity. Although there are several elegant syntheses of certain members of this group of alkaloids, a truly unified approach has yet to be developed. In short, general approaches to this compound class are hampered by a lack of complete control in setting the C(3) stereocentre at a late stage. Herein, we report that a functionalized hydrindanone enables a divergent strategy that builds on existing precedent to address this long-standing challenge. Utilizing an aminonitrile intermediate, the stereochemistry at C(3) of the yohimbinoid skeleton can be controlled effectively in a Pictet–Spengler reaction. We applied this approach to the first total syntheses of the C(3) epimeric natural products venenatine and alstovenine. A hydrindanone-based approach to yohimbinoid natural products has been developed. A judicious choice of reaction conditions — inspired by prior work by the Stork group — allows effective control of the stereochemistry at C3 of the yohimbinoid skeleton. This approach has resulted in the first total syntheses of the C3 epimeric natural products venenatine and alstovenine.

Cite this article

Lebold, T., Wood, J., Deitch, J. et al. A divergent approach to the synthesis of the yohimbinoid alkaloids venenatine and alstovenine. Nature Chem 5, 126–131 (2013). https://doi.org/10.1038/nchem.1528

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