Studies on Bergman cyclization, the chemistry at the heart of enediynes

The kinetics of Bergman cyclization (BC) which is dependent upon a number o f steric and stereoelectronic parameters, have been studied in various nitr ogen-substituted cyclic enediynes. The simplest of these, a 10-membered ene diyne 33 cyclized spontaneously (t(1/2) = 72 h at 23 degrees) and caused si gnificant cleavage of supercoiled double stranded DNA at micromolar level. The degree of pyramidalization of the ring nitrogen in these enediynes has an Inverse effect on the rate of cyclization. Replacement of the ene part w ith an aromatic ring led to a considerable elevation of activation energy f or BC.