STTR Phase II: Enzymatic Synthesis of Chiral Cyclopropanes for Pharmaceutical Drug Synthesis and Agricultural Crop Protection Applications

这个小企业创新研究（SBIR）项目的更广泛的影响/商业潜力是建立一个广泛适用的，突破性的生物催化技术，以生产一类重要的化合物，称为手性环丙烷。 环丙烷是合成药物、作物保护剂和高价值电子化学品的关键中间体。使用这项技术的产品每年的市场总额超过100亿美元。如果成功，正在开发的技术将为重要的化学产品创造更安全，更清洁，更可持续的路线，通过减少生产步骤，降低所需的资本投资，显着减少浪费来降低成本。用更高效和可持续的酶催化步骤取代现有的化学路线也将提高许多用于药物和作物保护化学品生产的高级药物中间体的纯度。该STTR第一阶段项目建议建立在第一阶段的结果基础上，其中使用新型工程酶开发了一种高效的生物催化工艺用于生产药物替格瑞洛。我们将创建一套扩大的环丙烷化生物催化剂，能够作用于更广泛的起始材料，从而扩大了这种新酶促反应的范围和实用性。完成替格瑞洛关键中间体生产工艺的开发和商业化，启动新型生物催化剂的开发工作，生产抗病毒药物的重要中间体。我们还将开发和商业化一套酶，可用于药物发现化学家建立下一代药物的有效途径。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is to establish a broadly applicable, breakthrough biocatalytic technology to produce an important class of compounds called chiral cyclopropanes. Cyclopropanes are key intermediates that are used in the synthesis of drugs, crop protection agents, and high-value electronic chemicals. Products accessible using this technology have markets totaling more than $10 billion annually. If successful, the technology under development will create safer, cleaner, more sustainable routes to important chemical products that will lower cost by reducing the number of production steps, lowering the required capital investment, significantly decreasing waste. Replacing existing chemical routes with the more efficient and sustainable enzyme-catalyzed steps will also improve the purity of many advanced pharmaceutical intermediates used in the manufacture of drugs and crop protection chemicals.This STTR Phase I project proposes to build on the results from Phase 1 in which a highly efficient biocatalytic process for the manufacture of the drug ticagrelor was developed using a novel, engineered enzyme. We will create an expanded set of cyclopropanation biocatalysts with the capability to act on a wider range of starting materials, thereby broadening the scope and utility of this new enzymatic reaction. We will complete the development and commercialization of the process for production of the key intermediate for ticagrelor and initiate work to develop novel biocatalysts to produce ley intermediates for anti-viral drugs. We will also develop and commercialize a set of enzymes that can be used by drug discovery chemists to establish efficient routes for next-generation drugs.