Catalytic asymmetric synthesis of febrifugine and isofebrifugine

Antimalarial alkaloids, febrifugine (1) and isofebrifugine (2), were synthe sized from simple achiral starting materials using tin(II)-catalyzed cataly tic asymmetric aldol reaction and lanthanide-catalyzed aqueous three-compon ent reaction as the key steps. These unambiguous total syntheses revealed t hat the absolute configurations of febrifugine and isofebrifugine were not (2'S, 3'R) and (2'R, 3'R) as reported previoussy but (2'R, 3'S) and (2'S, 3 'S), respectively. (C) 1999 Elsevier Science Ltd. All rights reserved.