Program in the chemoenzymatic synthesis of alkaloids and medicinal agents and the development of new chiral building blocks, asymmetric protocols, and reagents

我们的研究计划专注于通过环境友好的方法(绿色化学)为重要的药物化合物开发高效的制造协议。该计划的关键组成部分是生物催化(或生物转化)，即我们使用特殊的有机体(或分离的酶)在水介质中执行一些化学反应。我们使用这些工具以更少的步骤制造有用的物质，以更安全的过程产生更少的危险废物。*在未来五年，我们的计划将专注于以下几个方面：*通过生物催化，我们将使新的构建块对其他化学反应有用。我们还将开发一种新的方法，将罂粟植物中的生物碱成分转化为药用物质。酶将被用来从天然化合物中的氮中去除甲基，这是一个很难通过化学方法实现的过程。*我们将开发两种新的合成方法。(1)我们将从生物催化制成的一些积木中制造碳糖(在结构上与糖有关，有许多医药应用)。(2)我们将开发一个将酯转化为甲基的短过程。*在靶向合成方面，我们将设计和合成天然存在于石榴花家族各种植物中的化合物的新衍生物，并研究它们的作用模式。我们已经制造的一些产品具有抗癌特性。我们还将着手新一代吗啡相关物质的合成，这是我们有很多经验的领域。*在我们计划的其他项目中，我们将研究多酚原酮的构效关系，这是一种从伯德金李树皮中分离出来的具有生物活性的物质，是最近制备的。我们将完成河豚毒素的正式全合成，河豚毒素是河豚鱼中的一种强有力的神经毒素，我们将在其中更有效地制造用于另一种合成的关键中间体。我们将使用我们的生物催化过程中的构建块来制造用于催化材料和模板的手性聚合物。另一个长期目标是设计一种催化剂，作为我们生物催化项目中使用的酶的化学等价物。*我们的研究将有助于开发新的替代技术，通过生物方法和使用来自细菌、真菌和植物的酶来替代传统的特种化学品和药剂制造。这项研究将为制药行业和学术界未来的化学专业人员提供极好的培训。培训化学家的最好方法是通过全合成项目，让他们接触到制药业中遇到的各种情况和挑战。在我们的研究过程中出现的协作需要团队努力和满足时间表。这样的培训共同造就了优秀的专业人才。

Our research program is focused on developing efficient manufacturing protocols for important medicinal compounds by environmentally friendly methods (green chemistry). The key component of the program is biocatalysis (or biotransformations) where we use special organisms (or isolated enzymes) to perform some chemical reactions in aqueous medium. We use these tools to make useful substances in fewer steps by a safer process that produces less hazardous waste.***Over the next five years our program will focus on the following:*** By means of biocatalysis, we will make new building blocks useful for other chemical reactions. We will also develop a new method for converting alkaloid components of the poppy plant to medicinally useful substances. Enzymes will be used to remove a methyl group from the nitrogen in the natural compounds, a process that is difficult to achieve by chemical methods. *** We will develop two new synthetic methods. (1) We will make carbasugars (structurally related to sugars, with a number of pharmaceutical applications) from some of the building blocks made by biocatalysis. (2) We will develop a short process for converting an ester to a methyl group.*** In the area of target-oriented synthesis, we will design and synthesize new derivatives of compounds naturally occurring in various plants in the amaryllis family and study their mode of action. Some that we have already made have anti-cancer properties. We will also embark on a new generation of syntheses of morphine-related substances, an area in which we have a lot of experience. *** Among other projects in our program, we will study the structureactivity relationship of pleiogenone, a substance with biological activity isolated from the bark of Burdekin plum trees and recently prepared. We will complete a formal total synthesis of tetrodotoxin, the potent neurotoxin from puffer fish, where we will make more efficiently a key intermediate used in another synthesis. We will use building blocks from our biocatalytic processes to make chiral polymers to use in materials and templates for catalysis. Another long-term goal is to design a catalyst as a chemical equivalent of the enzyme that is employed in our biocatalysis projects. ******Our research will contribute to the development of new replacement technology for traditional manufacturing of specialty chemicals and pharmaceutical agents through biological methods and the use of enzymes from bacteria, fungi, and plants. The research will provide excellent training for future chemistry professionals both in the pharmaceutical industry and in academia. The best means of training chemists is offered by projects in total synthesis where they are exposed to a full set of situations and challenges encountered in pharmaceutical industry. Collaborations that emerge during our research require team effort and meeting of timelines. Together, such training produces outstanding professionals.