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: 7682969
• 负责人: Jon Antilla
• 金额: $ 25.9万
• 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/7682969
• 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; Essential Drugs; 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; 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; base; catalyst; chiral molecule; cost; design; drug candidate; imidazolone; innovation; interest; method development; public health relevance; 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）：参与生命生物化学的重要分子的重要部分具有“手性”，即它们主要以一种不可重叠的镜像形式存在。此外，大多数药物和候选药物也具有手性（手性），这些化合物的所有立体异构体通常都是合成的，并评价其生物活性。由于自然界的手性，候选药物的镜像形式可能具有截然不同的生物学效应。一种在使用中稳步增长的手性分子合成方法是在需要立体控制的关键步骤中应用通用的立体选择性催化方法。有机催化，使用小的有机（非金属基）分子作为催化剂是传统金属基催化的一个有吸引力的替代方案。这种方法已经发现了一些最近的成功和有机催化为基础的化学的持续评估显然是一个值得的奋进。自2004年以来，基于手性磷酸的有机催化剂的使用已被证明在越来越多的反应中提供优异的立体选择性。我们的努力一直参与新方法的发展，其中手性磷酸可以立体选择性地应用。该提案的具体目标分为设计，分析和改进一些新的反应，从而手性磷酸可以是有效的，立体选择性的催化剂。在每个新反应研究中也描述了新创建的手性产品的潜在健康相关效用。公共卫生关系：在这个提议中描述的化学解决了现代合成的一个基本的，重要的方面-三维（3-D）化学结构的控制。绝大多数“生命分子”和大多数药物都具有特定的3-D结构，必须控制这些结构以进行高效、低成本的合成。因此，允许这种控制的方法对公共卫生非常重要。