Synthesis and photo-Bergman cyclization of naphthylethynyl arenediynes

ORGN 363

Heather J. Walker and John D. Spence, jspence@csus.edu. Department of Chemistry, California State University Sacramento, 6000 J Street, Sacramento, CA 95819
The design of enediyne based antitumor agents that undergo controlled Bergman cyclization are highly attractive synthetic targets due to the ability of the resulting 1,4-phenyl diradical to cleave DNA. In particular, the development of photo-activated enediynes has played a key role in the selective activation of enediyne pro-drugs. It is well documented that 1,2-bis(phenylethynyl)benzene undergoes photo-Bergman cyclization with 300 nm light. In order to increase the wavelength of light employed for enediyne photocyclizations we have developed methodology to prepare a series of highly conjugated arenediynes. One approach towards achieving this goal incorporates one or two 1'-naphthyl or 2'-naphthyl substituents on the alkyne termini, generating a series of naphthylethynyl arenediynes. In addition to extending conjugation to facilitate photoactivation with 350 nm light, the bulkier naphthyl substituents can influence cyclization pathway as well as efficiency. The syntheses of naphthylethynyl arenediynes and their photochemical reactivity will be presented.