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: 6347539
• 负责人: ERIC A MINTZ
• 金额: $ 6.95万
• 依托单位: CLARK ATLANTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6347539
• 关键词: chemical structure function; chemical synthesis; cyclopentane; diene; drug design /synthesis /production; drug quality /standard; heavy metals; ligands; metal complex; organometallic compounds; pharmacology; physical chemical interaction; stereochemistry; stereoisomer

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 sole as a racemic mixture. One optical isomer produced the desired 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， 特别是制备对映体纯的化合物。 手性控制的重要性的最引人注目的例子之一 是使用药物沙利度胺，这是制造和唯一的， 外消旋混合物。 一种光学异构体产生所需的治疗药物 效应，而对映体，这被认为是不对称的， 惰性导致胎儿畸形 由于在以下方面的巨大差异 对映体可能产生的药理作用， 所有未来含有手性中心的药物将仅作为 所需的治疗活性对映异构体。 过渡金属有机金属配合物被广泛用于 有效地催化实验室和 工业规模。 利用手性药物 有机金属配合物进行对映选择性转化。 然而，阻止手性催化的主要障碍是， 实现这一潜力一直缺乏现成的 对映体纯的有机金属配合物。 本项目的目的是制备对映体纯的手性 取代的四甲基膦配体和对映体纯的 手性桥连的手性配体，并利用这些新的 对映体纯的手性配体制备新的手性基团IV 过渡金属配合物 然后，我们将研究这些 新的手性IV族过渡金属配合物， 化学计量和催化对映选择性有机合成， 目的是制定可用于综合 对映体纯的药剂。