Biomimetic syntheses of alkaloids
Borrerine-derived alkaloids such asor the flinderoles have shown significant antimalarial activity including in chloroquine-resistant strains of Plasmodium falciparum [1-6].
Using flow chemistry platforms, we have begun investigating the syntheses of these bisindol compounds and our initial results have shown that by passing a solution of borrerine through a cartridge containing a solid-supported Lewis acid we can obtain isoborreverine selectively without any purification.
1. Antimalarial activity of natural product extracts from Papua New Guinean and Australian plants against Plasmodium falciparum, L.S. Fernandez, M.F. Jobling, K.T. Andrew, V.M. Avery, Phytother. Res. 2008, 22, 1409–1412.
2. Flinderoles A-C: Antimalarial Bis-indole Alkaloids from Flindersia Species, L.S. Fernandez, M.S. Buchanan, A.R. Carroll, Y.J. Feng, R.J. Quinn, V.M. Avery, Org. Lett. 2009, 11, 329-332.
3. Antiparasitic activity of alkaloids from plant species of Papua New Guinea and Australia, L.S. Fernandez, M.L. Sykes, K.T. Andrew, V.M. Avery, Int. J. Antimicrob. Agents 2010, 36, 275-279.
4. Biomimetic Total Syntheses of Borreverine and Flinderole Alkaloids, D.H. Dethe, R.D. Erande, A. Ranjan, J. Am. Chem. Soc. 2011, 133, 2864-2867.
5. Synthesis of flinderoles B and C by a gold-catalyzed allene hydroarylation, R.M. Zeldin, F.D. Toste, Chem. Sci. 2011, 2, 1706-1709.
6. Biomimetic synthesis of the antimalarial flindersial alkaloids, R. Vallakati, J. A. May, J. Am. Chem. Soc. 2012, 134, 6936-6939.