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Synlett 1995; 1995(1): 13-26
DOI: 10.1055/s-1995-4842
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Design of Enediyne Prodrugs

Martin E. Maier*
  • *Fachbereich Chemie, Institut für Organische Chemie, Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 16, D-06120 Halle (Saale), Germany
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Publication History

Publication Date:
31 December 2000 (online)

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An important feature of the enediyne antitumor antibiotics is that a chemical activation step is necessary to allow the formation of cytotoxic diradicals to take place. Therefore they are interesting as lead compounds for the development of novel antitumor agents. This review discusses the activation principle of the natural enediynes and sorts out the factors that govern the reactivity of enediynes. It can be seen that steric as well as electronic effects can be used to modulate the reactivity of an enediyne. The known models that allow to estimate the steric effects on the reactivity are summarized. Moreover, the strategies that enable the generation of reactive enediynes from stable precursors are presented. These include the transformation of 1,5-diynes to enediynes, the removal of a bridgehead double bond (calicheamicin analogs) or the opening of an epoxide in a strained precursor (dynemicin analogs). Finally, enediyne prodrugs are presented that have originated by de-novo design.

Calicheamicin - esperamicin - dynemicin A - kedarcidin - antitumor compounds - macrocycles - enediynes - eneyne-allenes - 1,5-diynes - force-field calculations