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.

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Dr.Dinesh Pandithavidana is a Sri Lankan who received his Bachelor of Science degree(First Class, Hons)from University of Colombo in Sri Lanka. He obtained his Ph.D. degree under the supervision of Professor Vladimir Popik at the University of Georgia in USA. Currently he works a senior lecturer in chemistry at University of Kelaniya in Sri Lanka.