SYNTHESIS OF ANTITUMOR AGENTS

这项建议的主要目标是调查范围和 过渡金属卡宾几种反应的适用性 有机合成中的络合物，并将其用于 两个抗肿瘤药物家族成员的合成。一个 串联Diel-Alder/环己二烯酮环化序列为 建议开发一种综合方法来解决 诺萜二内酯A，那基内酯F， 那吉拉内酯D和波多利特。这将是第一位将军 对这类化合物的合成方法，应该是 足够灵活，以允许准备具有 功能的多样性。一条通向 提出了以a为关键步骤的拟喹啉内酯 卡宾配合物的环丙烷化反应及其合成 这类化合物的靶标是抗肿瘤药物贺利宁。 在其他一些目标中，还有开发一种 前列腺素的合成路线，下面将进行说明 前列腺素E_2的合成及环丙烷化反应 卡宾复合体。前列腺素家族有一个引人注目的 广泛的生理效应和特殊的兴趣 一直专注于炎症、生殖和过敏 回应。使这种方法成为可能的化学物质是 针对抗肿瘤药物合成的工作成果 赫利纳林探员。对洋茉莉素的合成也进行了努力。 为吡哆醇的合成提供了一条新的途径。 吡哆醛磷酸，其活性形式，作为辅因子 绝大多数的酶催化α-蛋白的化学变化。 氨基酸。最后，不对称Aldol，Diels的新方法- 过渡金属卡宾催化的Alder和Claisen反应 将对复合体进行调查。后者将是一项一般性研究 这是由这些反应的重要地位所保证的 坚持传统的合成有机方法论。

The chief objective this proposal is to investigate the scope and applicability of several reactions of transition metal carbene complexes in organic synthesis and to employ them in the synthesis of members of two families of antitumor agents. A tandem Diel-Alder/cyclohexadienone annulation sequence is proposed for development of a synthetic approach to the norditerpene dilactones wentilactone A, nagilactone F, nagilactone D, and podolide. This would be the first general synthetic approach to this family of compounds and should be flexible enough to allow for the preparation of members with a diversity of functionality. A synthetic route to the pseudoquaianolides is proposed that involve as the key step a cyclopropanation reaction of carbene complexes and the synthetic target in this class of compounds is the antitumor agent helenalin. Among some of the other objectives are the development of a synthetic route to the prostaglandins which will be illustrated by the synthesis of PGE2 and involves the cyclopropanation reactions of carbene complexes. The prostaglandin family has a remarkably broad range of physiological effects and special interests have been focused on inflammation, reproduction, and allergic responses. The chemistry that makes this approach possible was an outcome of the work directed to the synthesis of the antitumor agent helenalin. The efforts on the synthesis of helenalin also has lead to a new approach to the synthesis of pyridoxine which in pyridoxal phosphate, its active form, serves as cofactor for the great majority of enzymes catalyzing chemical changes in alpha- amino acids. Finally, new approaches to asymmetric aldol, Diels- Alder and Claisen reactions mediated by transition metal carbene complexes will be investigated. The latter will be a general study that is warranted by the important position that these reactions hold in traditional synthetic organic methodology.