Asymmetric Pd(II)-catalyzed Ring-forming Reactions

不对称 Pd(II) 催化的成环反应

• 批准号: 7671373
• 负责人: Ryan A Altman
• 金额: $ 4.72万
• 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 2011-09-07
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7671373
• 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（由申请人提供）：手性杂环化合物通常显示出有趣的生物学活动，并且通常在销售的药物中发现。这项研究的广泛目的是开发新的合成方法来制备手性杂环化合物，而这些化合物否则难以进入。这项研究的第一部分涉及开发不对称的PD（LL）催化的Sn2'替代性抗性三氯酰亚胺的位移，用C-H酸作为亲核试剂。随后，将采用该方法来以立体选择性的方式制备高肠酮C的连续第四纪立体中心。拟议研究的最后一部分将在级联反应中应用手性PD（LL） - 催化剂，以准备有用的杂环化合物。公共卫生相关性的许多新药物在过去10年中引入的许多新药物都被销售为单一剂量药物。此外，其中许多化合物都包含杂环结构。拟议的研究将为制药行业中的主要化学家提供科学家，这是用于制备单一南方异构体杂环化合物以及发现新药的新合成工具。