Synthesis of hybrids between the alkaloids rutaecarpine and luotonins A, B

Abstract

The synthesis of 7,12-dihydroindolo[2',3':3,4]pyrrolo[2,1-b]quinazolin-5-one, a hybrid compound containing common structural features of the natural alkaloids rutaecarpine (Evodia rutaecarpa) and luotonin A (Peganum nigellastrum), was performed by active methylene group transformations of deoxyvasicinone. The synthesis of 7-hydroxy-8-norrutaecarpine was accomplished via the first total synthesis of bouchardatine (Bouchardatia neurococca) and its acid-catalyzed ring closure. The synthesized alkaloid analogues are the first representatives of a new heterocyclic ring system. Preliminary testing of the synthesized compounds showed cytotoxic activities against HeLa cells and apoptosis inducing effects at a concentration comparable to that of the control drug, etoposide. (C) 2008 Elsevier Ltd. All rights reserved