TUMOR REMISSION--TAXOL AND CLOSE ANALOGS VIA SYNTHESIS

描述：紫杉醇及其结构上的近亲代表 实施从头合成战术的苛刻目标。这 是由于它们高度的结构复杂性和丰富的 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。没有一种可以被归类为特别有效。看起来似乎 提高综合效率的最好方法是减少合成的数量 必要的步骤，并利用高效的程序。首要目标 目前的努力之一是开发一种简短的紫杉醇路线，通过 处理至少两个中心重排，这已经得到证明 高度功能化的设置，能够满足规定的需求。 因此，这种方法是围绕着阐述 通过提交简单的紫杉烷1，2-加合物来提早整个紫杉烷环系 D-樟脑衍生物的顺序电荷加速氧合反应和 α-酮醇重排与新的、特别定制的反应一起进行。 紫杉素的合成利用了这些概念中的许多，已经 已经完成了。 该协议将在很大程度上依赖于D-樟脑的使用， 从樟树中分离出来的纯对映体商品，以便 以其适当的绝对构型生产目标化合物。 强调简洁性；因此，非常合理 区域控制和最低限度的保护/解除保护演习 已部署。灵活性也将是最重要的，这样，在 方法论将允许中间体适应到达 几个目标终端产品。 第一要务是到达紫杉醇。一旦找到了紫杉醇的路线 很明显并且进展顺利，实时将致力于结构 修改。辅助目标将包括准备 1-脱氧紫杉醇及其α-氧杂环丙烷异构体，其中D环与 Alpha-框架的表面。

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.