THE SYNTHESIS AND CHEMISTRY OF A SIMPLIFIED, FUNCTIONAL ANALOG OF NEOCARZINOSTATIN CHROMOPHORE - IDENTIFICATION OF AN INTRAMOLECULAR 1,5-HYDROGEN ATOM-TRANSFER RELEVANT TO THE MECHANISM AND CLEAVAGE SELECTIVITY OF DIYL-BASED DNA-CLEAVING AGENTS

The synthesis and chemistry of a monocyclic analogue of neocarzinostat in chromophore are described. This analogue is activated through a Mic hael addition process and provides cycloaromatized products similar to those obtained in the activation of neocarzinostatin chromophore. Mec hanistic studies on this analogue have led to the first identification of a diyl self-quenching pathway based on a 1,5-hydrogen atom transfe r that provides a novel hypothesis about the relationship between thio l structure and DNA single and double strand cleavage selectivity for neocarzinostatin chromophore and diyl-based cleaving agents.