Asymmetric Pd(II)-catalyzed Ring-forming Reactions

不对称 Pd(II) 催化的成环反应

• 批准号: 7919955
• 负责人: Ryan A Altman
• 金额: $ 3.54万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-08 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7919955
• 关键词: Acids; Biological; Development; Drug Industry; Heterocyclic Compounds; Marketing; Methodology; Methods; Pharmaceutical Preparations; Pharmacologic Substance; Preparation; Reaction; Research; Resolution; Scientist; Structure; catalyst; enantiomer; hyperolactone C; interest; public health relevance; tool

DESCRIPTION (provided by applicant): Chiral heterocyclic compounds typically display interesting biological activity, and are commonly found in marketed pharmaceuticals. The broad aim of this research is to develop new synthetic methods for preparing chiral heterocyclic compounds that are difficult to access otherwise. The first part of this research involves the development of an asymmetric Pd(ll)-catalyzed Sn2' displacement of prochiral allylic trichloroimidates with C-H acids as nucleophiles. Subsequently, this methodology will be applied to prepare the contiguous quaternary stereocenters of Hyperolactone C in a stereoselective fashion. The final section of the proposed research will apply chiral Pd(ll)-catalysts in cascade reactions to prepare useful heterocyclic compounds. PUBLIC HEALTH RELEVANCE Many new pharmaceuticals introduced in the last 10 years are marketed as single-enantiomer drugs. Further, many of these compounds contain heterocyclic structures. The proposed research will provide scientists, primarily medicinal chemists in the pharmaceutical industry, new synthetic tools for the preparation of single-enantiomer heterocyclic compounds and for the discovery of new drugs.

描述（申请人提供）：手性杂环化合物通常表现出有趣的生物活性，并且常见于市售药物中。本研究的主要目的是开发新的合成方法来制备难以获得的手性杂环化合物。本研究的第一部分涉及以C-H酸作为亲核试剂的前手性烯丙基三氯亚胺酯的不对称Pd（II）催化Sn 2 '置换的发展。随后，该方法将被应用于以立体选择性方式制备Hyperolactone C的连续四级立体中心。所提出的研究的最后部分将在级联反应中应用手性Pd（II）-催化剂以制备有用的杂环化合物。公共卫生相关性过去10年中推出的许多新药都是作为单一对映体药物上市的。此外，这些化合物中的许多含有杂环结构。拟议的研究将为科学家，主要是制药行业的药物化学家，提供制备单一对映异构体杂环化合物和发现新药的新合成工具。