New Stereoselective Reactions for Chiral Amine Synthesis

手性胺合成的新立体选择性反应

基本信息

批准号：
7817116
负责人：
Jeffrey Nicholas Johnston
金额：
$ 25.8万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
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/7817116
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 novel therapeutics public health relevance silane small molecule stannane therapeutic development tool

项目摘要

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）：该提案的总体目标是开发生成对映体富集的有机化合物的新方法。这些产品是更精细的小分子的有价值的前体，这些小分子是药剂和/或更复杂的生物活性天然产物。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洁合成。这些方法基于手性质子催化剂的开发，作为用于对映选择性合成的新型手性非外消旋试剂。该配合物是易于制备的有机催化剂，并且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。这些研究有可能影响小分子和“生物”治疗剂的合成。此外，这些方法能够无金属生产功能密集的单一对映体（和非对映体）有机化合物。公共健康相关性：该提案描述了手性小分子有机催化剂的开发以及相应的对映选择性反应。只需一步即可生成立体化学富集形式的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）。这些化学商品是生物活性天然产物、生物制剂和小分子治疗药物的常见亚单位。