TOTAL SYNTHESIS OF AEGYPTINONE-A AND AEGYPTINONE-B

This paper describes the first total syntheses of the diterpene quinones aegyptinones A and B via an extremely direct route which should easily accommodate the production of gram quantities of each compound. The key step in the synthetic strategy involves the application of a recently developed ''second-generation'' photochemical aromatic annulation method for the construction of highly substituted aromatic systems. The synthesis of one of the annulation components, the diazo ketone 5, was achieved using a Diels-Alder-based benzannulation strategy employing cyanoallene and the dienamine 13. Cyanoallene proved to be uniquely effective for this cycloaddition, which either failed or proceeded in poor yield using several substituted acetylenes as dienophiles. The pivotal aromatic annulation reaction was accomplished by irradiating a solution of the diazo ketone 5 and the readily available siloxyalkyne 4 in a Pyrex vessel with a 450-W medium-pressure Hanovia lamp at room temperature for 17-20 h. The desired tricyclic phenol 3 was produced in 58-70% yield and was then converted to aegyptinone B (2) by treatment with tetra-n-butylammonium fluoride in the presence of oxygen. Finally, cyclization to generate aegyptinone A was accomplished in high yield by brief exposure of 2 to an ethanolic solution of concentrated sulfuric acid at room temperature. Overall, this strategy provides efficient routes (six and seven steps, respectively) to aegyptinones A and B which should facilitate the systematic investigation of the pharmacological activity of these novel diterpenes.