Synthesis of alpha-aryl-substituted and conformationally restricted fosmidomycin analogues as promising antimalarials
Haemers, Timothy × Wiesner, Jochen Busson, Roger Jomaa, Hassan Van Calenbergh, Serge #
Wiley-v c h verlag gmbh
European journal of organic chemistry issue:17 pages:3856-3863
Fosmidomycin represents a new antimalarial drug that acts by inhibition of 1-deoxy-D-xylulose 5-phosphate reductoisomerase, an essential enzyme of the mevalonate-independent pathway of isoprenoid biosynthesis. This work describes the synthesis of a series of alpha-aryl-substituted fosmidomycin analogues that exhibit improved antimalarial activity. A linear synthetic route involving a 3-aryl-3-phosphorylpropanal intermediate proved practical to prepare these derivatives. A phospha-Michael addition to cyclopent-2-enone gave access to conformationally restricted analogues. (c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006.