Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Biomimetic synthesis

Flinderoles facilitated

J. Am. Chem. Soc. 134, 6936–6939 (2012)

The emergence of drug-resistant strains of Plasmodium falciparum — the major cause of severe malarial infections — has resulted in much interest in the flindersial alkaloids, which are thought to act by a different mechanism than the commonly used drug chloroquine. With a goal of further testing and developing these natural products, Ravikrishna Vallakati and Jeremy May from the University of Houston have now described a biomimetic synthesis of several members of this family of alkaloids.

Prior work on the biosynthesis of the related natural products borreverine and isoborreverine led Vallakati and May to propose that the biosynthetic origin of flinderole A is an acid-catalysed ring-opening of borrerine followed by dimerization in a formal [3+2] cycloaddition (as pictured). Acid treatment of borrerine produced flinderole A along with its diastereomer desmethylflinderole C (at the starred position) and isoborreverine. To their surprise, and contrary to the previous reports, very little borreverine itself was produced under these conditions. The results, however, reflect the fact that borreverine and the flinderoles are not found together in nature. Furthermore, the Diels–Alder reaction to form borreverine would be energetically unfavourable with respect to that forming isoborreverine.

A one-pot reaction involving methylation of borrerine prior to acid treatment gave flinderoles B and C, meaning that all of the antimalarial flindersial alkaloids can be synthesized in as few as three steps from three simple commercially available materials. This convergent synthesis should make it possible to vary each of these three components to easily make analogues of the flinderoles and thus allow their testing for antimalarial activity.

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Davey, S. Flinderoles facilitated. Nature Chem 4, 430 (2012). https://doi.org/10.1038/nchem.1370

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchem.1370

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing