High performance liquid chromatography station for rapid reaction analysis and optimization

拟议的研究作为其总体目标，通过开发新的反应，使用分子重排作为关键设计元素，为分子复杂性问题提供合成解决方案。 解决这些问题的方法将是双重的：i）我们将以具有重要生物学特性的复杂天然产物为目标，ii）我们将开发新的复杂性生成反应，这些反应应该对合成界有广泛的用途。具体来说，我们将开发皮质抑素A的合成，皮质抑素A是一种重要的天然产物，也是抗癌治疗药物开发的潜在领导者。 为了进行这种合成，设计了一种新的级联反应来处理目标化合物中存在的一些中心结构问题。 这项工作的成功完成将允许抗血管生成活性的生物学评价（与约克大学的塔拉哈斯教授合作）。此外，我们对开发使用顺序分子重排的复杂生成反应感兴趣。 由于这些反应提供了对映体富集的多取代手性碳环、杂环和非环状化合物的合成途径，因此有望得到广泛的应用。 HPLC分析已经取代了其他更耗时和更不准确的技术作为标准分析方法。 所要求的HPLC站将对我们的再验证成功产生重大影响。

The proposed research has as its overarching aim the provision of synthetic solutions to problems of molecular complexity by developing new reactions using molecular rearrangements as key design elements.  The approach to these problems will be twofold:  i) we will target complex natural products with important biological properties, and ii) we will develop new complexity generating reactions that should be widely useful to the synthetic community.Specifically, we will develop a synthesis of cortistatin A, an important natural product and potential lead for the development of anticancer-therapeutics.  To carry out this synthesis, a new cascade reaction has been designed to deal with some of the central structural issues present in the target compound.  Successful completion of this work will allow biological evaluation for anti-angiogenic activity (in collaboration with Professor Tara Haas of York University).In addition, we are interested in developing complexity-generating reactions using sequential molecular rearrangements.  These reactions are expected to have wide application by the community since they provide access to enantioenriched polysubstituted chiral carbocyclic, heterocyclic and acyclic compounds.Crucial to our work is the rapid analysis of multiple reactions in support of optimization.  HPLC analysis has supplanted other more time-consuming and less accurate techniques as the standard method of analysis.  The HPLC station requested will have a significant impact on the success of our reasearch.