New Stereoselective Reactions for Chiral Amine Synthesis

描述（由申请人提供）：本提案的总体目标是开发生成富集对映体有机化合物的新方法。这些产品是更精细的小分子药物制剂和/或更复杂的生物活性天然产物的有价值的前体。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。这些方法是基于开发手性质子催化剂作为对映选择性合成的新型手性、非外消旋试剂。这些配合物是很容易制备的有机催化剂，通常是稳定的固体。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，该方法使无金属生产功能致密的单一对映体（和非对映体）有机化合物成为可能。

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.