SYNTHESIS OF UNUSUAL BIOLOGICALLY ACTIVE TERPENES

这项研究的主要目标是继续发展， 高级水平的实用性[3，3] sigmatropy的建设， 结构类型多种多样的复杂萜烯。 这种方法 所有的迹象都表明这是一个非常重要的进步， 以一种简洁和 立体控制方式 这些新战略是基于进一步 利用阴离子氧-Cope和Claisen重排进行共- 结构不寻常的中型环系统组成的7-10 组成原子。 许多选定的潜在适用性 针对不同治疗领域的目标， 特别及时，是重要的补充理由。 一种利用串联技术合成黑色素B3的非常短的方法 动力学拆分和氧代Cope化学来构建中心 以立体控制的方式与适当的绝对 将检查配置。 同样，一个特别短的 一种快速构建桥头的脆化剂的合成方法 烯属烯丙基氢过氧化物被计划。 高度的趋同 描述了计划中的精加工蛋白酸和乙烯基酚的特性。 这 整个阴离子氧-Cope工艺的方面已经严重地 在过去的研究中被忽视，值得大量开发。 的 复杂的分子可以通过这种方式进行加工的速度 技术可能是无与伦比的。 这一策略也将在我们计划的方法中得到应用， 维雷西那明A.在这种情况下，两个必要的建筑之一， Blocks是天然存在的呋喃萜类吴茱萸酮。 在所有 在上述推力下，可以制备类似物以提供添加的 了解各自协议的灵活性。 扩大克莱森环的重新安排预计将促进 快速控制几种劳伦辛代谢物如劳伦炔和 异aureatin，以及尤加利烷的氧杂双环二萜类化合物 类型. 一种涉及新的双重Tebbe-Claisen序列的方法是， 开发并扩展到合成ceroplastrin I。最后， 脂环克莱森重排的双重采用是作为 是合成cleomdolide的关键立体化学决定因素。

The primary objective of this research is to continue to develop at an advanced level the utility of [3,3] sigmatropy for the construction of complex terpenes of widely varied structural type. This methodology gives every indication of being a very important advance in our ability to access diverse classes of important natural products in a concise and stereocontrolled manner. These new strategies are based on the further exploitation of the anionic oxy-Cope and Claisen rearrangements for con- struction of unusual medium-sized ring systems consisting of 7-10 constituent atoms. The latent applicability of many of the selected targets to various therapeutic areas make this phase of the program particularly timely and constitutes important added justification. An exceptionally short synthesis of cyathin B3 which exploits tandem kinetic resolution and oxy-Cope chemistry to construct the central seven-membered ring in stereocontrolled fashion with proper absolute configuration will be examined. In like fashion, an exceptionally short synthesis of crispolide that features rapid construction of bridgehead olefinic allylic hydroperoxides is planned. High levels of convergency characterize the planned elaboration of albolic acid and vinigrol. This aspect of the overall anionic oxy-Cope process has been seriously neglected in past studies and warrants considerable exploitation. The rapidity with which complex molecules can be elaborated by this technique is probably unrivaled. This tactic will also see service in our planned approach to verecynarmin A. In this instance, one of the two necessary building blocks is the naturally occurring furanoterpene evodone. In all of the above thrusts, analogues may be prepared in order o provide added insight into the flexibility of the respective protocols. Ring-expanding Claisen rearrangements are expected to facilitate the rapid contruction of several laurencin metabolites such as laurenyne and isolaureatin, as well as oxabicyclic diterpenoids of the eunicellane type. A process involving a novel two-fold Tebbe-Claisen sequence is to be developed and extended to a synthesis of ceroplastol I. Finally, two-fold adoption of the alicyclic Claisen rearrangement is to serve as the key stereochemical determinant in a projected route to cleomdolide.