Overseas Travel Grant: From Dendralenes to Antimicrobial Decalins (Visit to Research School of Chemistry, Australian National University)

细菌感染正变得越来越难以用现有的抗生素治疗，人们普遍认识到需要新的治疗方法。政府和世卫组织继续强调开发新抗生素是一个高度优先的领域。许多天然抗菌产品含有功能化的十氢化环系统。这些结构单元在综合上不容易构建，并且通常需要许多综合步骤。本文提出，在树突烯的合成和表征方面的最新进展可能使开发一种高效和通用的透射Diels-Alder方法，用于许多天然产物中存在的大范围功能化十氢化环体系。如果成功，这条路线可能会在这些稀缺分子的合成和供应方面取得突破，以进行全面的生物学评估。该提案将建立在我们之前epsrc资助的抗菌天然产物合成领域的工作基础上，并允许PI在Sherburn小组中度过一段时间，以获得合成和处理树烯的第一手经验，从而使用Diels-Alder反应合成具有生物活性的天然产物。这将使在合成含十calin的抗菌剂中使用树突烯的完整建议得以发展。

Bacterial infections are becoming increasingly hard to treat with current antibiotics and it is well recognised that new treatments are required. The government and the WHO continue to highlight the development of new antibiotics as an area of high priority. Many antimicrobial natural products contain functionalised decalin ring systems. These structural units are synthetically non-trivial to construct and oftentimes require many synthetic steps. It is proposed here that recent advances in the synthesis and characterisation of dendralenes may enable the development of a highly efficient and general transmissive Diels-Alder approach to a large range of functionalised decalin ring systems present in many natural products. If successful, such a route could lead to breakthroughs in the synthesis and supply of these scarce molecules for full biological evaluation. This proposal will build on our previous EPSRC-funded work in the area antimicrobial natural product synthesis and the use of Diels-Alder reactions for the synthesis of biologically active natural products by allowing the PI to spend a period of time embedded in the Sherburn group to gain first-hand experience in the synthesis and handling of dendralenes. This will enable a full proposal for the use of dendralenes in the synthesis of decalin-containing antimicrobials to be developed.