Point-to-Axial Chirality Transfer: Enabling Stereochemical Determinations and Enantioselective Reactions

点到轴手性转移：实现立体化学测定和对映选择性反应

• 批准号: 1856335
• 负责人: Babak Borhan
• 金额: $ 48万
• 依托单位: Michigan State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1856335&HistoricalAwards=false
• 关键词: Point; Axial; Chirality; Transfer; Enabling

In this project, funded by the Chemical Structure, Dynamics, and Mechanisms-B Program of the Chemistry Division, Professor Babak Borhan of the Chemistry Department at Michigan State University (MSU) is developing new methods to identify the chirality of organic molecules. Chirality, also referred to as handedness, is an important property of molecules. Human hands are not identical, but mirror images of each other (the two hands are not superimposable). The relationship between two objects that are mirror images of each other, have a center of chirality, and are referred to as enantiomers. There are numerous examples of enantiomers in biology and medicine. For example, Thalidomide, a drug that was used in the late 1960s and early 1970s, led to the embryonic mis-development of a number of babies is an example of a mixture of enantiomers. One of the enantiomers was biologically active as an anti-nausea agent to treat morning sickness in pregnant women. The other enantiomer was teratogenic, which interfered with the correct embryonic development. The drug was given as a mixture of the two enantiomers, causing tragedy. From this experience, scientists have learned that the ability to identify the chirality of a molecule is of utmost importance. The Borhan group is developing new methods to rapidly identify the chirality of organic molecules to ensure the safety of drugs such as Thalidomide. Professor Borhan organizes and leads Project SEED activities at MSU. Project SEED is a ten-week summer program funded in part through the American Chemical Society and various organizations at MSU, to support the research of high school students from financially-disadvantaged families. The goals of the project are to provide simple, rapid, efficient, and non-ambiguous procedures for the absolute stereochemical determination of chiral organic molecules, many of which are synthetic intermediates of bioactive compounds or newly isolated pharmacologically-active metabolites. The project relies heavily on Circular Dichroism (CD) as the tool for observing the host-guest interactions between the chiral compounds and the receptors. The functionalities of interest include chiral epoxides, phosphines, phosphine oxides, boranes, alkenes, alkynes, and alkyl arenes. In addition, the endowed helicity of the supramolecular complexes, induced through interactions with the bound asymmetric guest molecules, will be used towards asymmetric catalysis.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在这个项目中，由化学部化学结构、动力学和机制-B 项目资助，密歇根州立大学 (MSU) 化学系教授 Babak Borhan 正在开发识别有机分子手性的新方法。 手性，也称为旋手性，是分子的重要性质。 人的手并不完全相同，而是互为镜像（两只手不可重叠）。 两个互为镜像的物体之间的关系，具有手性中心，被称为对映体。生物学和医学中有许多对映体的例子。 例如，沙利度胺（Thalidomide），一种在 20 世纪 60 年代末和 70 年代初使用的药物，导致许多婴儿胚胎发育不良，就是对映体混合物的一个例子。 其中一种对映体具有生物活性，可作为抗恶心剂，用于治疗孕妇孕吐。 另一种对映异构体具有致畸性，会干扰胚胎的正确发育。 该药物以两种对映体的混合物形式给药，造成了悲剧。 从这次经验中，科学家们了解到识别分子手性的能力至关重要。 Borhan小组正在开发新方法来快速识别有机分子的手性，以确保沙利度胺等药物的安全性。 Borhan 教授在密歇根州立大学组织并领导 SEED 项目活动。 SEED 项目是一个为期十周的暑期项目，部分由美国化学会和密歇根州立大学的各个组织资助，以支持来自经济困难家庭的高中生的研究。 该项目的目标是为手性有机分子的绝对立体化学测定提供简单、快速、高效和明确的程序，其中许多是生物活性化合物的合成中间体或新分离的药理活性代谢物。 该项目很大程度上依赖圆二色性（CD）作为观察手性化合物和受体之间主客体相互作用的工具。 感兴趣的官能团包括手性环氧化物、膦、氧化膦、硼烷、烯烃、炔烃和烷基芳烃。 此外，通过与结合的不对称客体分子相互作用诱导的超分子复合物所赋予的螺旋性将用于不对称催化。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的评估进行评估，被认为值得支持。影响审查标准。

项目成果

Absolute stereochemical determination of 1,2‐diols via complexation with dinaphthyl borinic acid

通过与二萘基硼酸络合绝对立体化学测定 1,2-二醇

• DOI: 10.1002/chir.23223
• 发表时间: 2020-03
• 期刊: Chirality
• 影响因子: 2
• 作者: Torabi Kohlbouni, Saeedeh;Sarkar, Aritra;Zhang, Jun;Li, Xiaoyong;Borhan, Babak
• 通讯作者: Borhan, Babak

Zirconium-catalyzed asymmetric Kabachnik–Fields reactions of aromatic and aliphatic aldehydes

锆催化的芳香族和脂肪族醛的不对称Kabachnik-Fields反应

• DOI: 10.1039/d1sc03222d
• 发表时间: 2021-09-29
• 期刊: Chemical Science
• 影响因子: 8.4
• 作者: Dai Y;Zheng L;Chakraborty D;Borhan B;Wulff WD
• 通讯作者: Wulff WD

A chiroptical approach for the absolute stereochemical determination of P -stereogenic centers

绝对立体化学测定 P 立体中心的手性光学方法

• DOI: 10.1039/d0sc02940h
• 发表时间: 2021-02
• 期刊: Chemical Science
• 影响因子: 8.4
• 作者: Chakraborty, Debarshi;Gholami, Hadi;Sarkar, Aritra;Joyce, Leo A.;Jackson, James E.;Borhan, Babak
• 通讯作者: Borhan, Babak

Absolute Stereochemical Determination of Organic Molecules through Induction of Helicity in Host–Guest Complexes

通过主客体复合物中螺旋性的诱导来绝对立体化学测定有机分子

• DOI: 10.1021/acs.accounts.0c00650
• 发表时间: 2021-02
• 期刊: Accounts of Chemical Research
• 影响因子: 18.3
• 作者: Gholami, Hadi;Chakraborty, Debarshi;Zhang, Jun;Borhan, Babak
• 通讯作者: Borhan, Babak