PURE ENTANTIOMER GROUP IV TRANSITION METAL COMPLEXES FOR ETHICAL DRUG SYNTHESIS

用于合乎道德药物合成的纯对映异构体 IV 族过渡金属配合物

• 批准号: 3756233
• 负责人: ERIC A MINTZ
• 金额: --
• 依托单位: CLARK ATLANTA UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3756233
• 关键词: chemical structure function; cyclopentane; diene; drug design /synthesis /production; drug quality /standard; ligands; metal complex; organometallic compounds; pharmacology; physical chemical interaction; stereochemistry

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.

药剂制备中最困难的问题之一 在实验室或工业规模上是立体化学的控制和 特别是对映体纯化合物的制备。 之一 手性控制重要性的最引人注目的例子是 使用药物沙利度胺，该药物是作为外消旋体制造和销售的 混合物。 一种旋光异构体产生了所需的治疗效果，而 该对映体被认为是药理学惰性的，导致 胎儿畸形。 由于药理差异巨大 对映体可以产生的影响很可能所有未来的药物 含有手性中心的产品将仅以所需的形式出售 具有治疗活性的对映体。 过渡金属有机金属配合物广泛用于 有效催化实验室和实验室的有机转化 产业规模。 使用手性有巨大的潜力 有机金属配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 这种潜力是由于缺乏现成的对映体纯 有机金属配合物。 该项目的目的是制备对映体纯的手性 取代的四甲基环戊二烯基配体和对映体纯 手性桥连环戊二烯基配体，并利用这些新的 对映体纯的手性配体制备新的手性 IV 族 过渡金属络合物。 然后我们将研究这些的潜力 新型手性 IV 族过渡金属配合物进行化学计量 和催化对映选择性有机合成，目的是 开发可应用于合成的方法 对映体纯的药物制剂。