Catalytic asymmetric synthesis of febrifugine and isofebrifugine

Antimalarial alkaloids, febrifugine (1) and isofebrifugine (2), were synthesized from simple achiral starting materials using tin(II)-catalyzed catalytic asymmetric aldol reaction and lanthanide-catalyzed aqueous three-component reaction as the key steps. These unambiguous total syntheses revealed that 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.