Novel Catalysts for Asymmetric Allylic Alkylation

不对称烯丙基烷基化的新型催化剂

• 批准号: 6443627
• 负责人: PREMCHANDRAN H. RAMIYA
• 金额: $ 9.8万
• 依托单位: MEDICHEM LIFE SCIENCES
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6443627
• 关键词: alkylation; allyl compound; catalyst; chemical synthesis; combinatorial chemistry; imidazole; ligands; method development; palladium; stereoisomer; technology /technique development

DESCRIPTION (provided by applicant): Driven by the FDA regulations and the growing market, there is a demanding need for technology to produce chiral pharmaceutical intermediates. Pd-catalyzed enantioselective C-C, C-N and C-O bond forming substitutions at allylic positions (allylic substitution or allylation) are an important area of current research. Many enantiomerically pure therapeutic compounds and natural products can be synthesized by employing this methodology. The design, synthesis and screening of chiral ligands, have played a pivotal role in the development of asymmetric catalysis. In Phase I, we propose to develop a new class of chiral ligands, which will be evaluated in palladium catalyze asymmetric allylic substitution (allylation) based on a standard model reaction. In Phase II, we are going to optimize the ligands and the reaction conditions. In addition, we will extend the use of the catalysts to a wide range of substrates including important drug intermediates. In Phase III, we will explore the applications in pharmaceutical and the related chemical industries and commercialize the catalysts as well as the technology for industrial and academic use. PROPOSED COMMERCIAL APPLICATIONS: There is an increasing need for enantiomerically pure pharmaceutical drugs. MediChem proposes to develop novel chiral carbene-transition metal catalysts for asymmetric allylic alkylation to form stereoselective carbon-carbon, carbon-nitrogen and carbon-oxygen bonds. The proposed catalysts will help synthesize pharmaceutical drugs and intermediates to be more efficient and more friendly to our environment.

描述（由申请人提供）：由FDA法规和 不断增长的市场，对生产手性药物的技术有着苛刻的需求。 医药中间体Pd催化的C-C、C-N和C-O对映选择性 在烯丙基位置的键形成取代（烯丙基取代或 烯丙基化）是当前研究的重要领域。许多对映体 纯的治疗化合物和天然产物可以通过使用 这种方法。 手性配体的设计、合成和筛选，对手性药物的合成起着举足轻重的作用， 在不对称催化发展中的作用。在第一阶段，我们建议 开发一类新的手性配体，将在钯中进行评估 基于标准模型催化不对称烯丙基取代（烯丙基化 反应在第二阶段，我们将优化配体和反应 条件此外，我们将把催化剂的使用范围扩大到 包括重要药物中间体在内的一系列底物。在第三阶段，我们 将探索在制药和相关化学品中的应用 工业和商业化的催化剂以及技术， 工业和学术用途。 拟议的商业应用： 对对映体纯的药物的需求日益增加。MediChem提出开发用于不对称烯丙基烷基化以形成立体选择性碳-碳、碳-氮和碳-氧键的新型手性卡宾-过渡金属催化剂。这些催化剂将有助于合成更高效、更环保的药物和中间体。