STTR Phase I: ACC Synthesis - a Way to Create Safer, Efficacious and Inexpensive Single Enantiomers

该奖项由2009年美国复苏和再投资法案(公法111-5)资助。这个小企业技术转让(STTR)第一阶段项目提出了一种通过使用ACC手性助剂生产对映体纯酮的新方法。单一对映体药物的合成是药物开发的一个极其重要的方面。目前生产和/或分离单一对映体化合物的方法相当有限，而且这些现有方法可能昂贵且难以实现，因此阻碍了它们在大规模生产中的应用。ACCS可以很容易地从商业上可获得的起始材料中以高效和成本效益的方式合成。它们很容易引入母酮中，并且在移除后可以很容易地回收。此外，它们固有的反应性克服了当前方法的实际限制，使它们适合于工业应用。这项研究的更广泛影响是：开发和随后FDA批准新的治疗药物变得越来越困难。一种新药的研发成本现在超过8亿美元，FDA已经引入了更严格的法规和广泛的临床试验。此外，还发生了几起领先公司因其药物的集体诉讼而遭受重大财务损失的案例，这些药物在上市后造成了不可预见的副作用。制药业目前正在努力寻找解决方案，以克服药物开发领域的新挑战，公众看到的进展有限。我们的创新合成方法将促进单一对映体药物配方的生产，这将直接有助于为制药业面临的日益严重的危机找到解决方案。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).This Small Business Technology Transfer (STTR) Phase I project propose a new method of producing enantiomerically pure ketones through the use of ACC chiral auxiliaries. The synthesis of single enantiomer drugs is an extremely important aspect of drug development. Current methods to both produce and/or isolate single enantiomer compounds are quite limited, and those existing methods can be expensive and difficult to carry out, thus preventing their application on large scale manufacturing. ACCs can be readily synthesized from commercially available starting materials in an efficient and cost effective way. They are easily introduced into the parent ketone, and can be easily recycled upon removal. Moreover, their inherent reactivity overcomes the practical limitations of current methods, making them amenable to industrial applications.The broader impacts of this research are: Development and subsequent FDA approval for new therapeutic agents has become increasingly difficult. R&D costs for a new drug are now in excess of $800 million and FDA has introduced more strict regulations and extensive clinical trials. Additionally, there have been several cases of leading companies suffering significant financial losses because of class action lawsuits from their drugs causing unforeseen sideeffects after reaching the market. The pharmaceutical industry is currently struggling to find solutions to overcome the new challenges in the field of drug development and the public has seen limited advances. Our innovative synthetic method will facilitate the production of single enantiomer drug formulations, which can contribute directly to finding solutions to the growing crisis facing the pharmaceutical industry.