ASYMMETRIC SYNTHESIS AND ITS APPLICATIONS

A.具体目标。 两个基本过程经常遇到的 复杂的天然产物的合成是：1）（直接）创建一个 手性底物上的一个或多个手性中心，和2）两个手性中心的偶联 同时产生手性中心的手性片段。 这些任务 原则上，可以通过使用 手性外试剂 涉及手性试剂的反应提供 含有或不含有手性部分的产物 试剂. 如果是，则该试剂被称为“内部”，如果不是， “外部”。 为了证明这一原则，并实现更高的 立体化学控制水平，我们计划通过三个阶段进行。 第一阶段涉及C2对称硼烷的设计， 例如，在一个实施例中，纯手性反式-2，5-二甲基硼杂环戊烷及其检测 试剂在单和多不对称诱导方面。 的 待研究的反应包括：硼氢化、亲核羰基 加成、羟醛缩合反应、酮还原和Diels-Alder反应 反应 硼烷的工作将由硅烷的类似研究跟进 和锡烷。 第二阶段的目的是阐明一个 金属阳离子，其可以与烷氧基中的一个或两个螯合 连接到两个反应物上的取代基，例如，一对烯醇化物和一对 醛醇缩合反应中的醛。 金属阳离子螯合是一种复杂的 过程及其详细信息将提供一个综合策略 这与使用手性外部试剂是互补的。 最后 通过追求阶段1和阶段2积累的知识将是 用于修饰记录的莫能菌素的几个主要步骤， 利福霉素S合成和执行拟定的利福霉素A 合成. 这些合成的新版本将有望揭示我们的 试图进入下一代聚酮化合物合成。 莫能菌素， 利福霉素S和红霉素A因其显著的 抗生素活性。

A. Specific Aims. Two fundamental processes often encountered in the synthesis of complex natural products are: 1) the (direct) creation of a chiral center or centers on a chiral substrate, and 2) the coupling of two chiral fragments with concommitant creation of chiral centers. These tasks can, in principle, be achieved with high stereoselection by the use of a chiral external reagent. The reaction involving a chiral reagent provides the product which does or does not contain the chiral moiety of the reagent. If it does, the reagent is called "internal", and if not, "external". In order to demonstrate this principle and achieve a higher level of stereochemical control, we plan to proceed through three stages. The first stage is concerned with the design of boranes of C2 symmetry, e.g., homochiral trans-2,5-dimethylborolane, and examination of these reagents in terms of single and multiple asymmetric induction. The reactions to be investigated include: hydroboration, nucleophic carbonyl addition, the aldol reaction, ketone reduction, and the Diels-Alder reaction. This borane work will be followed by similar studies on silanes and stannanes. The second phase is aimed at elucidating the behavior of a metal cation which may chelate with either one or both of the alkoxyl substituents attached to two reactants, e.g., a pair of an enolate and an aldehyde in an aldol reaction. The metal cation chelation is a complicated process and its detailed information will provide a synthetic tactic complimentary to that using a chiral external reagent. Finally the knowledge that will accrue through the pursuit of stages 1 and 2 will be utilized to modify several major steps of the recorded monensin and rifamycin S syntheses and to execute the proposed erythronolide A synthesis. The new versions of these syntheses will hopefully disclose our attempts to enter a next generation of polyketide synthesis. Monensin, rifamycin S, and erythromycin A are well-known for their significant antibiotic activities.