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Conformational Control in Activation of an Enediyne

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journal contribution
posted on 07.08.2003, 00:00 by M. F. Semmelhack, Lingyun Wu, Robert A. Pascal, Douglas M. Ho
In the bicyclo[7.3.1]tridec-4-ene-2,6-diyne framework characteristic of calicheamicin, DFT calculations predict that the chair conformer should be much more reactive toward cycloaromatization compared to the boat form. A functionalized derivative of this framework with an added two-atom bridge to enforce the boat conformation was synthesized and shown to be stable at 23 °C. Cleavage of the bridge releases the conformational lock and cycloaromatization proceeds with t1/2 42.5 min/23 °C, presumably through the chair conformation. This confirms the prediction based on computation and points to a new principle for triggering the enediyne toxins.