SBIR Phase II: Multiplex Expansion of the Chiral Carbon Catalog Platform towards Stereo-enriched Non-propionate Chemical Classes and Industrial Applications

SBIR二期项目的更广泛/商业影响是开发工具和平台，以大规模生产有价值的化学构建块，用于合成具有挑战性的化合物，即聚酮化合物。这些化合物在制药、农化和兽医行业的多种适应症中具有多样化和强大的生物活性。这类课程的高影响力受到当前化学工艺效率低下的阻碍，无法完全解决其复杂结构。为了充分释放这类化合物的潜力，需要提高效率的改进化学物质，以成功识别高影响的候选物质，以便进一步开发。这一项目将有助于开发一类新型化合物作为抗菌剂和抗癌剂。该二期SBIR项目将扩大合成工具箱，以生产非经典聚丙酸聚酮构建块，目前无法大规模合成。提出的平台是一个合成工具箱，允许从简单的起始材料立体选择大规模经济合成各种复杂的聚丙酸构建块，允许大规模生产，而无需繁琐/昂贵的纯化和使用工业友好型结晶代替。该平台可以方便地监测反应过程，实现顺利的工艺生产，并避免使用成本高昂的手性助剂。该项目将扩展先前的工作，展示一套广泛应用的对映纯聚丙酸聚酮天然产物（PPNP）前体；这些前体被用来设计和合成潜在的抗微生物作物保护先导化合物。在拟议的工作中，我们将扩展我们的化学平台，以更多样化的前体集合，从而增强先导设计能力和优化。如果计算分析和合理设计需要合成新的化合物，这些目标将用我们的构建块来准备，这些构建块包括所有可能的阵列，而不仅仅局限于天然存在的化合物。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader/commercial impact of this SBIR Phase II project is to develop tools and platforms to produce valuable chemical building blocks for synthetically challenging compounds, known as polyketides, on large scales. These compounds have diverse and powerful biological activities across multiple indications within the pharmaceutical, agrochemical, and veterinary industries. The high impact of this class is hampered by the inefficiencies of current chemical processes to fully tackle their complex structures. To fully unlock the potential of this class of compounds, improved chemistries with greater efficiencies are required to successfully identify high impact candidates for further development. This project will enable the development of a novel class of compounds as antimicrobials and anticancer agents. This Phase II SBIR project will expanding a synthetic toolbox to produce non-classical polypropionate polyketide building blocks, which currently cannot be synthesized at scale. The proposed platform is a synthetic toolbox that allows stereoselective large-scale economic synthesis of various complex polypropionate building blocks from simple starting materials, allowing large-scale production without tedious/expensive purifications and using industrial-friendly crystallization instead. The platform allows easy monitoring of reaction progress, enables smooth process production, and avoids using the cost prohibitive chiral auxiliaries. This project will expand on previous work demonstrating one set of enantiopure polypropionate polyketide natural products (PPNP) precursors for broad applications; these precursors were used to design and synthesize potential lead compounds for anti-microbial crop protection applications. In the proposed work, we will expand our chemistry platform to a more diverse collection of precursors enabling enhanced lead design capabilities and optimization. If computational analysis and rational design call for synthesis of new compounds, these targets will be prepared with our building blocks, which include all possible arrays and are not restricted to naturally occurring compounds.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.