The Development of New Stereoselective Organocatalytic Processes

新型立体选择性有机催化工艺的发展

• 批准号: 7526718
• 负责人: Jon Antilla
• 金额: $ 28.15万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7526718
• 关键词: 3-Dimensional; Acids; Address; Amines; Area; Aziridines; Biochemistry; Biological; Biological Factors; Carbon; Catalysis; Chemical Structure; Chemistry; Cyclization; DNA Sequence Rearrangement; Development; Drug Design; Esters; Evaluation; Exhibits; Goals; Handedness; Health; Human; Human Resources; Hydrogen Bonding; Image; Imides; Imines; Indoles; Investigation; Ketones; Kinetics; Lead; Life; Literature; Metals; Methodology; Methods; Nature; Numbers; Outcome; Pharmaceutical Preparations; Pharmacologic Substance; Phosphoric Acids; Play; Procedures; Process; Proline; Public Health; Publishing; Pyrroles; Qualifying; Reaction; Reporting; Research; Resolution; Route; Scheme; Stereoisomer; Sulfonamides; Testing; Work; amidation; aziridine; base; catalyst; chiral molecule; cost; design; imidazolone; indole; innovation; interest; method development; small molecule; success; three dimensional structure

DESCRIPTION (provided by applicant): Significant portions of important molecules involved in the biochemistry of life have "handedness," i.e. they are primarily found in one nonsuperimposible mirror image form. Additionally, the majority of drugs and drug candidates also have handedness (chirality) and all stereoisomers of these compounds are normally synthesized and evaluated for biological activity. Due to the chirality of nature, the mirror image forms of drug candidates can have vastly differing biological effects. One approach to the synthesis of chiral molecules that is growing steadily in usage is the application of versatile, stereoselective catalytic methodology in key steps where stereocontrol is required. Organocatalysis, the use of small organic (non-metal based) molecules as catalysts is an attractive alternative to traditional metal-based catalysis. This approach has found a number of recent successes and the continued evaluation of organocatalytic-based chemistry is clearly a worthwhile endeavor. Since 2004 the use of chiral phosphoric acid-based organocatalysis has been shown to provide for excellent stereoselectivity in a growing number of reactions. Our efforts have been involved in the development of new methodology where chiral phosphoric acids can be applied stereoselectively. The specific aims of this proposal are divided into the design, analysis, and refinement of a number of new reactions whereby chiral phosphoric acids can be efficient, stereoselective catalysts. The potential health-related utility of the newly created chiral products are also described in each new reaction study. PUBLIC HEALTH RELEVANCE: The chemistry described in this proposal addresses a fundamental, important aspect of modern synthesis -- the control of three-dimensional (3-D) chemical structure. The vast majority of the "molecules of life" and most pharmaceutical drugs have specific 3-D structure that must be controlled for efficient, low cost synthesis. Therefore methods that allow for this control are very important for public health.

描述（由申请人提供）：生命生物化学涉及的重要分子的重要部分具有“交接性”，即它们主要以一种不耐用的镜像形式找到。此外，大多数药物和候选药物也具有惯用性（手性），并且这些化合物的所有立体异构体通常经过合成并评估生物学活性。由于大自然的手性，候选药物的镜像形式可能具有巨大不同的生物学作用。在使用中稳步生长的手性分子合成的一种方法是在需要立体控制的关键步骤中应用多功能的立体选择性催化方法。有机催化，将小有机（非金属）分子用作催化剂是传统金属催化的一种有吸引力的替代品。这种方法发现了许多最近的成功，基于器官的化学的持续评估显然是值得的。自2004年以来，使用手性磷酸的有机刻塔的使用可在越来越多的反应中提供出色的立体选择性。我们的努力参与了新方法的发展，在这些方法论中，手性磷酸可以立体选择应用。该提案的具体目的分为许多新反应的设计，分析和完善，从而有效地磷酸可以有效，立体选择性催化剂。每项新反应研究还描述了新创建的手性产品的潜在与健康相关的效用。公共卫生相关性：该提案中描述的化学涉及现代合成的基本，重要方面 - 对三维（3-D）化学结构的控制。绝大多数“生命分子”和大多数药物具有特定的3-D结构，必须控制高效，低成本的合成。因此，允许这种控制的方法对于公共卫生非常重要。