Alternatives to palladium catalysis for the elaboration of nitrogen heterocycles

在合成有机化学发展之前，有机化合物只能通过自然生物过程才能获得。随着化学科学的进步，特别是自20世纪50年代以来，非常复杂的分子现在可以很容易地合成出来，为人类提供药物和作物保护剂。目前，钯催化的成键反应是合成化学家用来制备所需有机化合物的最常用的技术之一，包括具有重要药用价值的杂芳烃衍生物，这些化合物占当今抗生素、抗癌、抗炎和其他药物的80%。尽管钯介导的方法已经成为一种广泛使用的合成工具，但钯金属价格昂贵，而且很难从药物制备所涉及的合成步骤中去除。通过这项建议，我们的目标是寻找替代方法来合成杂芳烃化合物，用于制药和化学工业。制药行业(如孟山都、辉瑞、百时美施贵宝、默克)正在使用我们实验室发现和开发的以前的方法，用于药物、农用化学品和其他商品化学品的多公斤商业生产。这项研究提案旨在帮助生产制造价格较低的药物的方法，从而为加拿大人提供健康和经济利益，并在此过程中为加拿大劳动力市场培训高素质的工人。

Prior to the development of synthetic organic chemistry, organic compounds were accessible only through natural biological processes. With the advancement of the chemical sciences especially since the 1950s, molecules of great complexity can now be readily synthesized providing medicines and crop protection agents for the benefit of humankind. Currently, palladium-catalyzed bond forming reactions are one of the most popular techniques used by synthetic chemists to prepare desired organic compounds, including pharmaceutically important heteroaromatic derivatives which constitute 80% of today's antibiotics, anticancer, anti-inflammatory and other medicinal agents. Although palladium-mediated methods have become a widely used synthetic tool, palladium metal is expensive and can be difficult to remove from the synthetic steps involved in drug preparation. Through this proposal, we aim to find alternative methods to synthesize heteroaromatic compounds for their use in the pharmaceutical and chemical industry. Previous methods discovered and developed in our laboratories are being used by the pharmaceutical industry (e.g. Monsanto, Pfizer, BMS, Merck) for the multikilogram commercial production of drugs, agrochemicals, and other commodity chemicals. This research proposal aims to help produce methods to make less expensive drugs and hence provide health and economic benefits to Canadians and, in the process, train highly qualified workers for the Canadian labour market.