LIGNAN ANTITUMOR PROTOTYPES VIA DIANION INTERMEDIATES

本提案的具体目标是综合一系列 越来越具有挑战性的木酚素天然产品， 高效制备两种抗肿瘤原型：steganacin和 鬼臼毒素 这些序列的发展应该特别证明 用于探索类似物之间的结构-活性关系， 这些有前途的特工 二价阴离子中间体对 亲电体 初步研究表明，羧酸 二价阴离子可以简单地通过改变 添加的I2的化学计量。 在这个简单的转变的基础上， 许多对称地和非对称地提交的琥珀酸 衍生物（包括酸酐、内酯和酰胺）容易变得 available. 在steganacin和steganacin的生成中探索的关键合成步骤 鬼臼毒素包括酰胺二价阴离子与2-碘羧酸盐反应， 选择性还原所得的酸-酰胺产物，和 使用N-碘酰胺分子内光化学驱动的碘化 前体

The specific goal of this proposal is the synthesis of a series of increasingly challenging lignan natural products culminating in the efficient preparation of two antitumor prototypes: steganacin and podophyllotoxin. Development of such sequences should prove especially useful for exploration of structure-activity relationships among analogs to these promising agents. Dianion intermediates exhibit extraordinary reactivity towards electrophiles. Preliminary studies have demonstrated that carboxylic acid dianions can be either dimerized or iodinated simply by varying the stoichiometry of added I2. Building upon this simple transformation, numerous symmetrically- and unsymmetrically-submitted succinic acid derivatives (including anhydrides, lactones, and amides) become readily available. Key synthetic steps to be explored in the generation of both steganacin and podophyllotoxin include reaction of amide dianions with 2-iodocarboxylates, selective reduction of the resulting acid-amide products, and intramolecular photochemically-driven iodination using N-iodoamide precursors.