M. Jung, S. Dansereau
1994
Citations
0
Influential Citations
16
Citations
Journal
Heterocycles
Abstract
A new route for the synthesis of benzo[h]-1,6-naphthyridines is described. The method involves the intramolecular Diels-Alder cycloaddition of aryl oxazoles with substituted acrylamides to give pyridines and was developed as a route to the antileukemic aromatic alkaloid 2-bromoleptoclinidinone. In 1987 Bloor and Schmitz published the structure of a novel brominated pentacyclic aromatic alkaloid 2bromo-leptoclinidinone (1).3 This compound, isolated from an ascidian, showed good cytotoxicity vs. PS (ED50 0.4 μg/ml). Because of its unusual structure and good biological activity, we began a program in 1988 aimed at the total synthesis of 1 and its analogues. However, in 1988, Kobayashi and coworkers isolated a closely related antileukemic alkaloid, ascididemnin, from a marine tunicate and determined its structure to be 2.4 The appearance of this new report prompted Schmitz to reexamine the structural assignment and in 1989, a structural revision was published indicating 3 as the correct structure for 2-bromoleptoclinidinone.5 We wish to report here the full details of our approach to the synthesis of the original structure of 2-bromoleptoclinidinone (1), a route which involves the intramolecular Diels-Alder cycloaddition of aryl oxazoles to give benzo[h]-1,6naphthyridines.