Biomimetic approach toward the stereoselective synthesis of acetogenins

Orru, R. V. A.; Groenendaal, Bas; van Heyst, J.; Hunting, Mark; Wesseling, C.; Schmitz, R. F.; Mayer, S. F.; Faber, K.

doi:10.1351/pac200375020259

Pure Appl. Chem., 2003, Vol. 75, No. 2-3, pp. 259-264

http://dx.doi.org/10.1351/pac200375020259

Biomimetic approach toward the stereoselective synthesis of acetogenins

R. V. A. Orru¹*, Bas Groenendaal¹, J. van Heyst¹, Mark Hunting¹, C. Wesseling¹, R. F. Schmitz¹, S. F. Mayer² and K. Faber²

¹ Department of Chemistry, Vrije University Amsterdam, De Boelelaan 1083, NL-1081 HV, Amsterdam, The Netherlands
² Department of Chemistry, University of Graz, Heinrichstrasse 28, A-8010, Graz, Austria

Abstract: Acetogenins isolated from the Annonaceae family of tropical trees have drawn considerable attention owing to their broad spectrum of biological activities. They are structurally characterized by the presence of one to three tetrahydrofuran rings in the center of a long (partly hydroxylated) hydrocarbon chain that ends in a (functionalized) butenolide moiety. Here we describe some of our results toward the first asymmetric total synthesis of cis-gigantrionenin, a principal acetogenin. In this approach, an enzyme-catalyzed epoxide hydrolysis and an enzyme-triggered double cyclization are crucial and give stereoselective access to essential chiral building blocks.