The Critical Distance for the Cycloaromatization Reactions of Enediynes

Title: The Critical Distance for the Cycloaromatization Reactions of Enediynes

Volume: 8 Issue: 6

Author(s): Joseph F. Capitani, Shannon M. Gaffney, Lyana Castaldo and Abhijit Mitra

Affiliation:

Keywords: Enediynes, cycloaromatization, Hopf cyclization, Myers-Saito cyclization, Bergman cyclization, critical distance model, antitumor antibiotics, QSAR

Abstract: It has been shown that the enediyne anticancer antibiotics e.g., calicheamicin, neocarzinostatin and others cleave DNA via the putative intermediate 1,4-diradical formed in the Bergmann cyclization and are thus useful for cancer chemotherapy. The pharmacological activity of these drugs is based, in general, on the activation of the pharmacophore and the subsequent cyclization leading to the formation of a radical, the rate of which is, in part, based on the terminal distance of the 1,5-diyne functionality, also known as the critical distance. But the critical distance alone cannot govern the rate of cyclization of the enediynes. A theoretical model has been developed to predict the rate of cyclization, and the thus the pharmacological activity, of these antibiotics based on the critical distance and the energy of activation.

Cite this article as:

Capitani F. Joseph, Gaffney M. Shannon, Castaldo Lyana and Mitra Abhijit, The Critical Distance for the Cycloaromatization Reactions of Enediynes, Current Topics in Medicinal Chemistry 2008; 8 (6) . https://dx.doi.org/10.2174/156802608783955719