Novel chiral materials for chromatographic applications

用于色谱应用的新型手性材料

• 批准号: 364971-2008
• 负责人: Crudden, Catherine
• 金额: $ 14.36万
• 依托单位: Queen's University
• 依托单位国家: 加拿大
• 项目类别: Strategic Projects - Group
• 财政年份: 2008
• 资助国家: 加拿大
• 起止时间: 2008-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=406440
• 关键词: Novel; chiral; materials; chromatographic; applications

Chiral chromatography is used to separate enantiomers, which are chemical compounds that are identical to each other except in the orientation of the atoms in space. Enantiomers are virtually indistinguishable in terms of physical properties (melting point, boiling point, spectroscopic data, etc.) but, when placed in a biological environment they can have hugely different properties. In the case of Thalidomide, one enantiomer cures morning sickness, one causes birth defects. In ethambutol, one enantiomer treats tuberculosis, the other causes blindness. The reason for this is that our biochemical machinery is made up of pure enantiomers of amino acids, which can recognize the different enantiomers. Thus pharmaceutical companies need to determine the biological activities of both enantiomers, and in general need to either prepare them in pure form, which is difficult, or separate them. Early on in the process of screening drug candidates, where pure forms of one or the other enantiomer are needed for testing, companies do not want to invest significant amounts of time investment to develop an efficient route since this time may be wasted if the compound fails a toxicity screen. Basically, the more quickly a compound can be made, the more quickly it can be screened for bioactivity and toxicity. Therefore efficient methods of enantiomeric separation, like preparative scale chiral chromatography are critical in the early stages of chiral drug development. With modern screening technology, an effective separation method can be found within days as opposed to the months that it may take to develop a highly effective enantioselective synthesis. Thus we propose to develop a novel type of chiral stationary phase. The material is an organic/inorganic composite with pores in the nano/meso region. It is prepared by condensation of chiral biaryl-based monomers around a surfactant template which is used to introduce porosity and control structure. The students involved in this project will be trained in organic synthesis, in order to make the chiral monomers, and in materials and analytical chemistry. They will have close interactions with our partners, Merck Frosst and Silicycle, the largest chromatography company in Canada.

手性色谱用于分离对映异构体，对映异构体是除了原子在空间中的取向之外彼此相同的化合物。对映异构体在物理性质（熔点、沸点、光谱数据等）方面几乎无法区分。但是，当它们被放置在生物环境中时，它们会有非常不同的特性。在沙利度胺的情况下，一种对映体治疗晨吐，一种导致出生缺陷。在乙胺丁醇中，一种对映体治疗肺结核，另一种导致失明。这是因为我们的生化机制是由氨基酸的纯对映体组成的，它可以识别不同的对映体。因此，制药公司需要确定两种对映异构体的生物活性，并且通常需要以纯形式制备它们，这是困难的，或者将它们分离。在筛选候选药物的过程的早期，其中需要一种或另一种对映异构体的纯形式用于测试，公司不想投入大量的时间投资来开发有效的途径，因为如果化合物未能通过毒性筛选，则可能会浪费时间。基本上，一种化合物越快被制造出来，就越快被筛选出生物活性和毒性。 因此，高效的对映体分离方法，如制备规模的手性色谱法，在手性药物开发的早期阶段至关重要。利用现代筛选技术，可以在几天内找到有效的分离方法，而不是开发高效的对映选择性合成可能需要几个月。因此，我们建议开发一种新型的手性固定相。该材料是具有纳米/介观区域中的孔的有机/无机复合材料。它是通过手性联芳基基单体在表面活性剂模板周围缩合制备的，该模板用于引入孔隙率和控制结构。参与该项目的学生将接受有机合成方面的培训，以制造手性单体，以及材料和分析化学。他们将与我们的合作伙伴Merck Frosst和加拿大最大的色谱公司Silicomp密切互动。