TUMOR REMISSION--TAXOL AND CLOSE ANALOGS VIA SYNTHESIS

描述：紫杉醇及其结构上的近亲代表了 要求重新合成战术的实施目标。 这 是其高度结构复杂性和丰富性的结果 立体化学细节 发展到现在的路线是 设计主要是为了证明紫杉醇可以在 实验室 没有一个可以被归类为特别有效的。 看似 提高整体合成效率的最佳方法是减少 必要的步骤，并利用高效的工艺。 首要目标 目前的努力之一是开发一种简化的紫杉醇路线， 解决至少两个中央重新安排问题， 高度功能化的设置能够满足所述需求。 因此，该方法是围绕制定 整个紫杉烷环系统早期提交简单的1，2-加合物 D-樟脑衍生物与顺序电荷加速的氧代Cope和 alpha-ketol重排旁边的新的，特别定制的反应。 利用这些概念中的许多概念合成红豆杉素， 完成了 该方案将严重依赖于D-樟脑的使用，D-樟脑是一种廉价的， 从樟树中分离的对映体纯的商品，以 以其正确的绝对构型产生目标化合物。 重点是要放在简洁;因此，非常合理 区域控制和最低限度的保护/解除保护机动将被 部署。 灵活性也是至关重要的，因此， 方法将允许中间体适应到达 几个目标产品。 第一要务是找到紫杉醇。 一旦找到紫杉醇的途径 很明显，进展顺利，真实的时间将用于结构 修改. 辅助目标将包括编制 1-脱氧紫杉醇及其α-氧杂环丁烷基异构体，其中D环稠合至 框架的α表面。

DESCRIPTION: Taxol and its close structural relatives represent very demanding targets for the implementation of de novo synthetic tactics. This is a consequence of their high structural complexity and abundant stereochemical detail. The routes developed to the present time were designed primarily to demonstrate that taxol can be prepared in the laboratory. None can be categorized as particularly efficient. Seemingly the best way to improve overall synthetic efficiency is to reduce the number of requisite steps and utilize highly efficient processes. The primary goal of the present effort is to develop an abbreviated route to taxol by addressing at least two central rearrangements, which have been demonstrated highly functionalized settings to be capable of meeting the stated needs. The approach is therefore one designed around the tactic of elaborating the entire taxane ring system early by submitting simple 1,2-adducts of D-camphor derivatives to sequential charge-accelerated oxy-Cope and alpha-ketol rearrangements alongside new, specifically tailored reactions. A synthesis of taxusin, which takes advantage of many of these concepts, has been completed. The protocol will rely heavily on the use of D-camphor, an inexpensive, enantiomerically pure commodity isolated from the camphor tree, in order to produce the targeted compounds in their proper absolute configuration. Emphasis is to be placed on brevity; consequently, very reasonable regiocontrol and a minimum of protection/deprotection maneuvers are to be deployed. Flexibility will also be paramount, such that minor changes in methodology will allow for adaptation of the intermediates to arrival at several targeted end-products. The first priority is to arrive at taxol. Once the route to taxol is made evident and is progressing well, real time will be devoted to structural modifications. The ancillary objectives will include the preparation of 1-deoxytaxol and its alpha-oxetanyl isomer where the D ring is fused to the alpha-surface of the framework.