ANTI-INFLAMMATORY AGENTS, ANTIBIOTICS AND PHEROMONES VIA VINYL METALLOIDS

本文提出的研究重点是新技术的发展。 利用特殊指令的综合方法论 类金属基团的性质以协调高度的 在给定的条件下对立体化学过程的控制 化学反应。这些原则将从以下几个方面进行研究 经典反应，如Wittig烯化，不对称 硼氢化反应和定向羟醛缩合反应。综合 从酰基硅烷/叶立德中分离高纯度的Z-乙烯基硅烷 这些化合物为反式烯醇的新路线提供了基础 信息素，因此，说明了新的，互补的作用 在Wittig中用酰基硅烷与醛的比较 主要产生顺式产物的烯化反应。展期 这种获得酰基锡衍生物的方法应该提供 立体定义的乙烯基锡化合物可以转化为以下一种 欧洲榆树的手性聚集信息素组分 树皮甲虫通过不对称的氢化硼作用。此外，通过 立体定义的β，β-不对称硼氢化反应 双取代乙烯基硅烷，一种新的、通用的光学- 活性抗炎药，如萘普生、布洛芬和Six 提出了相关的商品化产品。该方法利用 硅基与氢取代基在反应中心的不对称性 在给出的过程中传授非对映面选择性 在较远的贝塔碳处不对称诱导。另一个 研究方面利用了以下几个新方面的优势 立体定义的硅烷化乙烯基硼烷 到有望给出三个选择性的交叉的烯醇硼烷 羟醛产物与醛的反应，导致 多氧抗生素。另一方面，新的概念在 空间定向的烷基硅烷的交叉Aldol反应 从酰基硅烷的E-烯醇酸盐的观点来看，或从烯醇- 预计酰基硅烷的组合将扩大 现在，Aldol将军选择了这些抗生素的路线。因此，它的主旨是 这项研究旨在通过实例果断地证明 类金属基团在指导 在重要的化学反应中遵循了精确的路线。此外， 在这里选择研究的反应中，进一步 将制定新的发展计划，以便学习化学原理 可在未来应用于新的合成靶标。

The research proposed herein focuses upon the development of new synthetic methodology which utilizes the special directive properties of metalloidal groups to orchestrate a high degree of control on the stereochemical course which is followed in a given chemical reaction. These principles are examined with respect to classic reactions such as the Wittig olefination, asymmetric hydroboration and the directed aldol condensation. The synthesis of Z-vinylsilanes in high isomeric purity from acylsilane/ylide combinations provides the basis for new routes to trans-alkenol pheromones, and thus, illustrates the novel, complementary role played by acylsilanes compared to aldehydes in the Wittig olefination which give predominately cis products. Extension of this approach to acyltin derivatives should provide access to stereodefined vinyltin compounds which can be converted to one of the chiral aggregation pheromone components of the European elm bark beetle through an asymmetric hydroboration. Moreover, through the asymmetric hydroboration of stereo-defined beta, beta- disubstituted vinylsilanes, a new, general route to optically- active anti-inflammatory agents such as Naproxen, Ibuprofen and six related commercial products is proposed. The approach utilizes the dissymmetry of silyl vs hydrogen substituents at the reaction site to impart diastereofacial selectivity in the process which gives asymmetric induction at the more remote beta carbon. Another aspect of the research takes advantage of several new aspects of stereo-defined silylated vinylboranes which either can be converted to enolboranes which are expected to give threo-selective crossed aldol products with aldehydes, reactions which lead to polyoxygenated antibiotics. On the other hand, new concepts in sterically-directed crossed aldol reactions of acylsilanes either from the standpoint of E-enolates of acylsilanes or from enolate- acylsilane combinations are expected to enhance the scope of the now-general aldol route to these antibiotics. Thus, the thrust of this study is to decisively demonstrate by example the important role that can be played by a metalloidal group in directing the precise course followed in important chemical reactions. Moreover, in the reactions selected for study herein, the basis for further developments will be laid so that the chemical principles learned can be applied to new synthetic targets in the future.