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

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.