PHOTOSWITCHABLE NINE-MEMBERED CYCLIC ENEDIYNES AND ENYNE-ALLENES

The extreme cytotoxicity of natural enediyne antibiotics is attributed to the ability of the (Z)-3-ene-1,5-diyne fragment incorporated into a 10- or 9-membered ring cyclic system to undergo Bergman cyclization and producing dDNA-damaging p-benzyne diradical. The rate of this reaction strongly depends on the ring size. Thus 11-membered ring enediynes are stable, 10-membered ring analogs undergo slow cycloaromatization under ambient conditions or mild heating. Very little is known about reactivity of 9-membered ring enediynes due to their instability. We have developed thermally stable photo-precursors of 9-membered enediynes, in which one of the triple bonds is replaced by the cyclopropenone group. UV irradiation of the photo-precursor results in the efficient decarbonylation and the formation of reactive enediyne. The latter undergoes clean cycloaromatization spontaneously with absence of any chemical additives. Synthetic strategies of a series of cyclopropenone containing nine-membered enediyne precursors and DNA-cleavaging activity of the photo-generated enediynes have been also discussed.

Autorentext

El Dr. Dinesh Pandithavidana es un srilankés que obtuvo su licenciatura en ciencias (primera clase, con honores) en la Universidad de Colombo, en Sri Lanka. Obtuvo su doctorado bajo la supervisión del profesor Vladimir Popik en la Universidad de Georgia en los Estados Unidos. Actualmente trabaja como profesor titular de química en la Universidad de Kelaniya en Sri Lanka.