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.

该创新-技术转化伙伴关系（PFI-TT）项目的更广泛影响/商业潜力是开发一种天然产品系列化合物，可用作各种携带疾病的蚊子、跳蚤、白蚁、各种蜱和鹿蜱（莱姆病携带者）的驱虫剂。这一系列化合物基于葡萄柚和阿拉斯加黄雪松皮的天然产物，已经被证明比现有的商业驱虫剂更安全、更有效。这类化合物目前通过发酵工艺生产，并用作风味/芳香组分，但对于消费者驱虫剂来说仍然太贵。该提案提出了一个现有的八步化学合成的母体化合物的家庭（诺卡酮），沿着计划，以大大简化，优化和降低成本与此合成。该项目的成功完成将导致生产成本的降低，接近其他商业驱虫剂的价格范围。此外，这一过程将破坏这种化合物家族的风味/香味市场，可能导致更广泛的采用。两个博士学生将通过参加NSF I-Corps和其他培训活动接受创新和创业培训。拟议的项目将能够在现有的实验室规模合成的基础上实现商业化，首先，大大修改八个合成步骤中最昂贵的步骤，目前认为这一反应需要一次性的、非常昂贵的和强碱性的可溶性催化剂系统。使用过去40年开发的多相催化技术，这种系统将被替换为更便宜的催化剂，也更容易从反应产物中分离出来。这种单一作用又可以用于降低其他合成中的制造成本（例如，医药中间体）。在许多其它方式中，在该合成中的其它过于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发生器和冷却器，通过溶剂替代，通过在选择性氧化反应中更好地控制氧化剂（臭氧），以及通过在某些工艺分离步骤中减少溶剂负载，这将通过使用现代自动快速色谱分离单元而成为可能。所有这些对合成的修改都是为了简化和优化化合物的合成，该项目由创新伙伴关系（PFI）计划和刺激竞争力研究的既定计划（EPSCoR）共同资助。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的评估被认为值得支持。影响审查标准。