PFI-TT: Chemical Synthesis of a Natural Product Family of Compounds for Tick-Targeted Prevention and Control

PFI-TT：用于蜱目标预防和控制的天然产物化合物家族的化学合成

• 批准号: 2345757
• 负责人: Kerry Dooley
• 金额: $ 55万
• 依托单位: Louisiana State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-03-01 至 2026-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2345757&HistoricalAwards=false
• 关键词: PFI; TT; Chemical; Synthesis; Natural

The broader impact/commercial potential of this Partnerships for Innovation - Technology Translation (PFI-TT) project is the development of a natural product family of compounds that can serve as insect repellent for various disease-carrying strains of mosquitos, fleas, termites, diverse ticks, and deer ticks, which are carriers of Lyme disease. This family of compounds, based on natural products derived from grapefruit and Alaskan yellow cedar bark, is already proven to be both safer and more effective than existing commercial repellents. This family of compounds is currently produced by fermentation processes and is used as flavor/fragrance components, but it is still too expensive for consumer insect repellents. The proposal presents an existing eight-step chemical synthesis for the parent compound of the family (nootkatone), along with a plan to greatly streamline, optimize and reduce the costs associated with this synthesis. The successful completion of this project will lead to the reduction of the production costs close to the price range of other commercial insect repellents. Furthermore, this process will disrupt the flavor/fragrance market for this compound family, possibly leading to wider adoption. Two Ph.D. students will be trained in innovation and entrepreneurship by participating in the NSF I-Corps and other training activities. The proposed project would enable commercialization based on the existing bench-scale synthesis by, first, greatly modifying the most expensive of the eight synthetic steps, a reaction currently thought to require a throwaway, highly expensive and strongly basic soluble catalyst system. This system would be replaced, using heterogeneous catalytic technology developed over the last 40 years, with a far cheaper catalyst that would also be easier to separate from the reaction products. This single action could in turn be applied to reduce manufacturing costs in other syntheses (e.g., pharma intermediates). In many other ways, other overly complex or expensive steps in this synthesis will be optimized to reduce reagent and solvent costs, in some cases by the use of a commercial ozonizer and chiller, by solvent substitutions, by better oxidant (ozone) control in the selective oxidation reactions, and by the reduction in solvent loadings in certain process separation steps, which will be made possible by the use of a modern automated flash chromatographic separation unit. All these modifications to the synthesis have been designed to streamline and optimize the synthesis of the compound, and to generate purer nootkatone products.This project is jointly funded by Partnerships for Innovation (PFI) program and the Established Program to Stimulate Competitive Research (EPSCoR).This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这种伙伴关系对创新 - 技术翻译（PFI-TT）项目的更广泛的影响/商业潜力是开发天然产物的化合物家族，可以用作各种疾病的蚊子，跳蚤，白蚁，多样的tick虫和鹿tick虫的驱虫剂，是莱姆病的携带者。这个化合物家族基于源自葡萄柚和阿拉斯加黄色雪松树皮的天然产品，已经被证明比现有的商业驱虫剂更安全，更有效。该化合物家族目前是由发酵工艺生产的，被用作风味/香料组件，但对于消费者驱虫剂来说，它仍然太昂贵了。该提案为家族的父院（Nootkatone）提供了现有的八步化学合成，以及大大简化，优化和降低与此合成相关的成本的计划。该项目的成功完成将导致降低生产成本接近其他商业驱虫剂的价格范围。此外，此过程将破坏这个化合物家族的风味/香水市场，这可能会导致更广泛的采用。两位博士学生将通过参加NSF I-Corps和其他培训活动来接受创新和创业的培训。拟议的项目将基于现有的台式综合构成商业化，首先要大大改变了八个合成步骤中最昂贵的最昂贵，这一反应目前被认为需要一个抛弃，昂贵且非常基本的可溶性催化剂系统。使用过去40年中开发的异质催化技术将取代该系统，并具有便宜的催化剂，从而更容易与反应产品分离。这项单一动作反过来又可以降低其他合成中的制造成本（例如，制药中间体）。在许多其他方面，该合成中的其他过度复杂或昂贵的步骤将被优化，以降低试剂和溶剂成本，在某些情况下，通过使用商业臭氧和冷却器，通过溶剂替代，通过在选择性氧化反应中进行更好的氧化剂（臭氧（臭氧）控制，以及通过在某些过程中减少溶液载荷的方法，通过溶剂（臭氧）的控制，可以通过一定的氧化载荷进行临时分离，从而可以使用液体分离，从而可以使用液体的分离来实现一定的使用。所有对合成的修改都设计为简化和优化化合物的合成，并生成更纯净的Nootkatone产品。该项目由创新合作伙伴关系（PFI）计划（PFI）共同资助，并既定的计划and既定的计划，以刺激NSF的Intervantorial Inturnition the Inderitore teem deem deem deem的竞争奖，以刺激竞争性研究。影响审查标准。