Bicyclo[3.3.0]octenones in synthesis. An approach to the synthesis of the antitumor sesquiterpene quadrone

Abstract

A synthetic approach to the antitumor sesquiterpene quadrone (1), based on intramolecular Michael reaction from a C-6 substituted bicyclo[3.3.0]oct-1 (2)-en-3-one [viz.(2)] is outlined. The preparations of the bicyclo-octenones (33b), (33a), and (41), precursors of (14), (15), and (16) respectively, are described, but attempts to induce these substrates [and the nitrone (42)]to undergo intramolecular Michael reactions to the carbocyclic ring system in quadrone, met with total failure.

Treatment of the bromo ketone (58) with methanolic sodium methoxide resulted in smooth intramolecular alkylation producing the tricyclic dione (59) containing the carbocyclic ring system in quadrone (1).