Novel chiral materials for chromatographic applications

手性色谱法用于分离对映体，对映体是除了原子在空间中的方向不同之外彼此完全相同的化合物。对映体在物理性质（熔点、沸点、光谱数据等）方面几乎是无法区分的，但是，当置于生物环境中时，它们的性质可能会有很大的不同。以沙利度胺为例，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，另一种会导致失明。这是因为我们的生化机械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，制药公司需要确定这两种对映体的生物活性，并且通常需要以纯形式制备它们，这是困难的，或者分离它们。在筛选候选药物的早期，需要一种或另一种对映体的纯形式进行测试，公司不希望投入大量的时间投资来开发有效的途径，因为如果化合物没有通过毒性筛选，这段时间可能会被浪费。基本上，一种化合物制备得越快，对其生物活性和毒性的筛选就越快。因此，有效的对映体分离方法，如制备级手性色谱法，在手性药物开发的早期阶段至关重要。有了现代筛选技术，有效的分离方法可以在几天内找到，而不是几个月，它可能需要开发一个高效的对映选择性合成。因此，我们提出开发一种新型的手性固定相。该材料是一种有机/无机复合材料，在纳米/介观区有孔。它是由手性双芳基单体在表面活性剂模板周围缩合而成的，表面活性剂模板用于引入孔隙度和控制结构。参与这个项目的学生将接受有机合成的训练，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默克弗罗斯特和加拿大最大的色谱公司Silicycle密切互动。

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.