New Stereoselective Reactions for Chiral Amine Synthesis

手性胺合成的新立体选择性反应

• 批准号: 8110644
• 负责人: Jeffrey Nicholas Johnston
• 金额: $ 25.45万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8110644
• 关键词: 3-hydroxybutanal; Acetic Acids; Acids; Aldehydes; Alkanes; Alkenes; Ally; Amines; Amino Acids; Area; Binding; Biological Factors; Carbon; Catalysis; Chemicals; Chemistry; Companions; Complex; Development; Diamines; Drug Formulations; Electronics; Enzymatic Biochemistry; Enzymes; Esters; Face; Foundations; Future; Glycine; Goals; Hydrogen Bonding; Imines; Investigation; Ketones; Knowledge; Length; Ligands; Mediating; Metals; Methods; Mission; Modeling; Names; Nitrogen; Parents; Phosphonic Acids; Production; Proliferating; Protocols documentation; Protons; Reaction; Reagent; Resort; Route; Silanes; Solid; Solutions; Solvents; Stilbenes; System; Therapeutic; Therapeutic Agents; Toluene; Variant; Work; aminophosphonate; analog; base; catalyst; chemical synthesis; design; enantiomer; enol; functional group; improved; insight; meetings; model development; molecular recognition; nitroalkane; public health relevance; silane; small molecule; stannane; therapeutic development; tool

DESCRIPTION (provided by applicant): The overarching goal of this proposal is the development of new methods to generate enantioenriched organic compounds. These products are valuable precursors to more elaborate small molecules that are medicinal agents and/or more complex biologically active natural products. The proposed methods specifically target the concise synthesis of 1-amino acids, 1,2-diamino acids, 1-aminophosphonic acids and chiral secondary amines. These methods are based on the development of chiral proton catalysts as new chiral, non-racemic reagents for enantioselective synthesis. The complexes are readily prepared organocatalysts, and are often bench stable solids. They are metal free, and therefore may be referred to as organic catalysts. These studies have the potential to impact the synthesis of both small molecule and "biologic" therapeutic agents. Moreover, the methods enable the metal-free production of functionally dense, single enantiomer (and diastereomer) organic compounds. PUBLIC HEALTH RELEVANCE: This proposal describes the development of chiral small molecule organocatalysts and the corresponding enantioselective reactions. In a single step, chiral nonracemic secondary amines and their derivatives (1-amino acids, 1-aminophosphonates, 1,2- diamino acids) are produced in stereochemically enriched form. These chemical commodities are common subunits of biologically active natural products, biologics, and small molecule therapeutics.

描述(由申请人提供)：这项提案的首要目标是开发新的方法来产生对映体富集型有机化合物。这些产品是更精细的小分子药物和/或更复杂的生物活性天然产品的宝贵前体。所提出的方法专门针对1-氨基酸、1，2-二氨基酸、1-氨基膦酸和手性仲胺的简明合成。这些方法是基于手性质子催化剂作为新的手性、非外消旋试剂用于不对称合成的发展。这些络合物是容易制备的有机催化剂，通常是工作台稳定的固体。它们不含金属，因此可称为有机催化剂。这些研究有可能对小分子和“生物”治疗剂的合成产生影响。此外，该方法能够无金属地生产功能稠密的单一对映体(和非对映异构体)有机化合物。 与公众健康相关：这项建议描述了手性小分子有机催化剂的发展和相应的对映选择性反应。在一步反应中，手性非外消旋仲胺及其衍生物(1-氨基酸、1-氨基膦酸酯、1，2-二氨基酸)以立体化学富集化的形式生成。这些化学产品是生物活性天然产物、生物制品和小分子疗法的共同亚单位。