NATURAL AND NONNATURAL DNA-CLEAVING AGENTS

建议合成和研究天然和非天然的成员， 一类能够在生理条件下形成双自由基的化合物 条件与串联目标（1），以增加我们对 这些物质切割DNA的详细机制， 抗肿瘤剂;和（2）通过化学合成提供新的结构 作为潜在的DNA切割剂和设计的先导进行研究 新的抗肿瘤药物。这是一个多方面的计划， （a）新制癌素的合成 发色团、其配基及发色团的非天然衍生物 核心;（B）动力霉素及相关结构的合成和研究;（c） 非天然DNA切割剂的设计和合成;（d）机理 天然和非天然DNA裂解剂的研究。

It is proposed to synthesize and study natural and nonnatural members of a class of compounds capable of forming biradicals under physiological conditions with the tandem goals (1) to increase our understanding of the detailed mechanisms by which these substances cleave DNA and function as antitumor agents; and (2) to provide by chemical synthesis new structures for study as potential DNA cleaving agents and as leads for the design of new antitumor agents. This is a multifaceted program which is composed of the following subdivisions: (a) Synthesis of Neocarzinostatin Chromophore, its Aglycone, and Nonnatural Derivatives of the Chromophore Core; (b) Synthesis and Study of Dynemicin and Related Structures; (c) Design and Synthesis of Nonnatural DNA Cleaving Agents; (d) Mechanistic Studies of Natural and Nonnatural DNA Cleaving Agents.