TOTAL SYNTHESIS OF AEGYPTINONE-A AND AEGYPTINONE-B

This paper describes the first total syntheses of the diterpene quinon es aegyptinones A and B via an extremely direct route which should eas ily accommodate the production of gram quantities of each compound. Th e key step in the synthetic strategy involves the application of a rec ently developed ''second-generation'' photochemical aromatic annulatio n 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 employ ing cyanoallene and the dienamine 13. Cyanoallene proved to be uniquel y effective for this cycloaddition, which either failed or proceeded i n 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 treatme nt with tetra-n-butylammonium fluoride in the presence of oxygen. Fina lly, cyclization to generate aegyptinone A was accomplished in high yi eld by brief exposure of 2 to an ethanolic solution of concentrated su lfuric acid at room temperature. Overall, this strategy provides effic ient routes (six and seven steps, respectively) to aegyptinones A and B which should facilitate the systematic investigation of the pharmaco logical activity of these novel diterpenes.