PURE ENTANTIOMER GROUP IV TRANSITION METAL COMPLEXES FOR ETHICAL DRUG SYNTHESIS

药剂制备中最难解决的问题之一 在实验室或工业规模上是立体化学和 尤其是对映体纯化合物的制备。其中之一 手性控制的重要性最戏剧性的例子是 药物沙利度胺的使用，该药物是作为外消旋制造和销售的 混合物。一种光学异构体产生了理想的治疗效果，而 这种被认为是药理惰性的对映体导致了 胎儿畸形。因为在药理上的巨大差异 对映体可以产生的效果很可能是所有未来的药物 含手性中心的将仅作为所需的 具有治疗活性的对映体。 过渡金属有机金属配合物被广泛应用于 在实验室和实验室中高效催化有机转化 工业规模。使用手性有巨大的潜力 有机金属络合物进行对映选择性转化。 然而，阻碍手性催化实现的一个主要障碍是 这种潜力一直是缺乏现成的对映体纯品 有机金属络合物。 该项目的目的是制备对映体纯手性。 取代的四甲基环戊二烯配体及其对映体纯度 手性桥联环戊二烯配体及其利用 手性纯手性配体合成新的手性基团IV 过渡金属络合物。然后，我们将研究这些技术的潜力 新型手性IV族过渡金属络合物进行化学计量 和催化对映体选择性有机合成，目的是 开发可用于合成的方法学 对映体纯药剂。

One of the most difficult problems in the preparation of medicinal agents on the laboratory or industrial scale is the control of stereochemistry and in particular the preparation of enantiomerically pure compounds. One of the most dramatic examples of the importance of chirality control was the use of the drug thalidomide, which was manufactured and sold as a racemic mixture. One optical isomer produced the desire therapeutic effect, while the enantiomer, which was assumed to be pharmacologically inert, led to fetal deformities. Because of dramatic differences in pharmacological effects that enantiomers can produce it is likely that all future drugs that contain chiral centers will be sold as only the desired therapeutically active enantiomer. Transition metal organometallic complexes are widely utilized to efficiently catalyze organic transformations on both the laboratory and industrial scale. There is tremendous potential for using chiral organometallic complexes to carry out enantioselective transformations. However, a major hurdle that has prevented chiral catalysis from fulfilling this potential has been the lack of readily available enantiomerically pure organometallic complexes. The aims of this project are to prepare enantiomerically pure chiral substituted tetramethylcyclopentadienyl ligands and enantiomerically pure chiral bridged cyclopentadienyl ligands, and to utilize these new enantiomerically pure chiral ligands to prepare new chiral group IV transition metal complexes. We will then examine the potential of these new chiral group IV transition metal complexes to carry out stoichiometric and catalytic enantioselective organic synthesis, with the aim of developing methodologies that can be applied to the synthesis of enantiomerically pure medicinal agents.