SYNTHESIS OF BRIDGED AND POLYCYCLIC ANTITUMOR AGENTS

我们研究的长期目标是发现新的 合成络合物的化学战略和战术 天然产品。我们的重点是结构的合成 已知或可能在体内具有抗癌活性。我们建议 首次全合成天然紫杉烷二萜， 紫杉素，并构建临床抗癌的类似物 药物紫杉醇。我们概述了一种新的药物合成方法。 弗雷德霉素A(目前正由NCI开发)和 抗有丝分裂药物秋水仙碱，两者都采用自由基偶联 骑自行车运动。还提出了新的手性合成方法。 抗肿瘤抗生素恶唑霉素和新恶唑霉素。我们 描述了一种立体控制的体内手性方法 抗肿瘤大环抗生素兰卡西丁C基于 光学活性β-内酰胺的分子内重排 中级的。热和钯(II)介导法的应用 对本课题组开发的环烯基化方法进行了测试 在拟议的萜类多毛酸、广藿香酮的合成中 还有Sanadaol。钩吻类化合物的一般合成 特别是甘尔斯丁和钩吻精素，预计是基于 我们实验室的最新结果涉及立体控制的 N-甲氧基缩醛衍生物的分子内环化反应 奥克辛多利。

The long-term objectives of our research are to discover new chemical strategies and tactics for the synthesis of complex natural products. Our focus is on the synthesis of structures known or likely to have in vivo anticancer activity. We propose to carry out the first total synthesis of a natural taxane diterpene, taxusin, and to construct close analogs of the clinical anticancer drug taxol. We outline a novel synthesis of the drug Fredericamycin A (currently under development by NCI) and of the antimitotic agent colchicine, both employing radical coupling cyclizations. Also proposed are chiral syntheses of the new antitumor antibiotics oxazolomycin and neooxazolomycin. We described a stereocontrolled chiral approach to the in vivo antitumor macrocyclic antibiotic Lankacidin C based on the intramolecular rearrangement of an optically active Beta-lactam intermediate. Applications of the thermal and Pd (II)-mediated cycloalkenylation methodologies developed in our group are tested in proposed syntheses of the terpenes hirsutic acid, patchoulenone and sanadaol. General syntheses of Gelsemium aldaloids, in particular gelsedine and gelsemine, are anticipated based on recent results from our laboratories involving the stereocontrolled intramolecular cyclizations of acetal derivatives of N-methoxy oxindoles.