Development of new methods for the synthesis of biologically active natural products

天然产品对人类健康的重要性怎么强调都不过分。世纪，加拿大人平均预期寿命几乎翻了一番，这在很大程度上归功于基于天然产品的医学进步，在过去25年中，FDA批准的药物中有50%以上是天然产品，或者其来源可以追溯到天然产品。生物化学和分子生物学的最新进展，包括用于快速鉴定生物活性化合物的高通量测定法的发展，使得许多具有迷人的生物活性和结构多样性的新天然产物的发现成为可能。然而，由于可从天然来源获得的材料的量通常是有限的，或者与收获生产生物体相关的环境问题，这些发现的完全实现依赖于在实验室中组装生物活性化合物所必需的合成化学或全合成的同时突破。因此，通过全合成，有机化学家提供了天然产物的可再生来源，并产生足够的数量用于明确的结构分配和彻底的生物测试。考虑到这一点，我们的研究计划的主要重点是天然产品的全合成，这些天然产品代表了治疗人类疾病的潜在主要候选人，以及为杀虫剂提供地球友好替代品的昆虫性信息素。这些研究在很大程度上依赖于创新反应的发展，这将使我们能够以简单的化学构建模块以简单的方式构建复杂的天然产物。特别是，我们计划开发的反应，将提供快速获得haterumalide，一种潜在的抗癌剂;风信子A5，一种潜在的抗糖尿病剂;和chimonanthine，一种镇痛天然产物。我们对这些分子的灵活合成也将使我们能够产生新的物质，这些物质在结构上与这些天然产物相似，但具有潜在的改善药物特性。该计划的成功实施将使我们对有机化学和药物开发的基本理解成为基础。

It is difficult to overstate the importance of natural products to human health. The near doubling of the life expectancy for the average Canadian in the 20th century is largely attributed to medical advances based on natural products and over 50% of drugs approved by the FDA in the past 25 years are, or their origins can be traced to, natural products. Recent advances in biochemistry and molecular biology, that includes the development of high-throughput assays for rapidly identifying biologically active compounds, has enabled the discovery of many new natural products with a fascinating range of biological activities and structural diversity. However, due to often-limited amounts of material available from the natural source or environmental concerns associated with harvesting the producing organism, the full realization of these discoveries relies on simultaneous breakthroughs in synthetic chemistry, or total synthesis, necessary to assemble the biologically active compound in the laboratory. Thus, through total synthesis organic chemists provide a renewable source of the natural product, and generate sufficient quantities for unambiguous structural assignment and thorough biological testing. Bearing this in mind, the major focus of our research program is the total synthesis of natural products that represent potential lead candidates for the treatment of human diseases, and insect sex pheromones that provide earth-friendly alternatives to insecticides. These studies rely heavily on the development of innovative reactions that will allow us to construct complex natural products in a straightforward manner from simple chemical building blocks. In particular, we plan to develop reactions that will provide rapid access to haterumalide, a potential anticancer agent; hyacinthacine A5, a potential antidiabetic agent; and chimonanthine, an analgesic natural product. Our flexible syntheses of these molecules will also allow us to generate new substances, similar in structure to these natural products but with potentially improved pharmaceutical properties. The successful implementation of this program will enable discoveries fundamental to our basic understanding of organic chemistry and the development of pharmaceuticals.