Efficient synthetic approach to new tricyclic spiroketone scaffolds

ORGN 677

Guo-Hua Chu, ghchu@adolor.com, Minghua Gu, Bertrand Le Bourdonnec, and Roland E. Dolle. Department of Chemistry, Adolor Corporation, 700 Pennsylvania Drive, Exton, PA 19341

 

4-Oxospiro[benzopyran-2,4'-piperidines] 1 are very useful scaffolds in drug discovery. This core structure is found in class III antiarrhythmics, alpha 1A-adrenergic receptor antagonists, 5-HT2A receptor antagonists and delta opioid receptor agonists. The synthesis of 4-oxospiro[benzopyran-2,4'-piperidines] 1 is well documented in the literature. There is no general method reported to prepare the tricyclic spirotetralones 2 (n = 1), congeners of 1 with isosteric replacement of the ring oxygen with a methylene group. We report a general and efficient synthetic approach to the novel tricyclic spiroketones with the general structure 2.