ASYMMETRIC SYNTHESIS AND ITS APPLICATIONS

A.具体目标。中经常遇到的两个基本过程 复杂天然产物的合成是：1)(直接)生成一种 手性底物上的一个或多个手性中心，以及2)两个 具有手性中心的承诺创建的手性片段。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了 不含或不含手性部分的产品 试剂。如果是这样的话，这种试剂就被称为“内部”，如果不是的话， “外部”。为了论证这一原则，并实现更高的 立体化学控制水平，我们计划分三个阶段进行。 第一阶段涉及C2对称性的硼烷的设计， 例如，同手性反式-2，5-二甲基硼烷，并对其进行检测 试剂在单次和多次不对称诱导方面。这个 待研究的反应包括：氢化硼化、亲核羰基 加成反应、Aldol反应、酮还原和Diels-Alder反应 反应。在这项硼烷工作之后，将对硅烷进行类似的研究。 和锡烷。第二阶段的目的是阐明 可与其中一个或两个烷氧基螯合的金属阳离子 连接到两个反应物上的取代基，例如一对烯醇和一对 醛在羟醛反应中。金属阳离子络合是一个复杂的过程。 流程及其详细信息将提供一种综合策略 与使用手性外部试剂的情况相辅相成。最后是 通过追求阶段1和阶段2而积累的知识将是 用于修改记录的莫能菌素的几个主要步骤 利福霉素S合成并执行建议的赤藓内酯A 综合。这些合成的新版本有望揭示我们的 试图进入下一代聚酮合成。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.