Cytotoxicity of natural enediyne antibiotics is attributed to the ability of the (Z)-3-ene-1,5-diyne or (Z)-1,2,4-heptatrien-6-yne fragments to undergo cycloaromatization producing DNA-damaging 1,4-diradicals. Lack of selectivity, however, hampers clinical applications of these natural products. In situ photochemical generation of reactive enediynes or enyne-allenes allows for achieving spatial selectivity of antibiotic action. In the course of the development of such photoswitchable enediynes, our group has encountered several interesting mechanistic phenomena: � Tautomerization of b-keto enediynes into allene-enynes, followed by the spontaneous Myers-Saito cyclization;� Complete suppression of the Bergman cyclization of ynamine-containing enediynes in favor of nucleophilic cycloaromatization;� Very fast ring-opening of 1,4-didehydro-2,3-cyclopentenonaphthalene resulting in rapid equilibration between this diradical and corresponding 9-membered ring enediyne precursor;� Dual reactivity of 9- and 10-membered ring allene-enynes. The outcome of their facile Myers-Saito cyclization depends on the polarity of the media.

Mechanistic adventures in enediyne chemistry

239th National Meeting (2010)

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