New Methodologies for the Synthesis of Biologically Active Amino Derivatives

生物活性氨基衍生物合成新方法

• 批准号: 7793571
• 负责人: MARGARITA ORTIZ-MARCIALES
• 金额: $ 13.41万
• 依托单位: UNIVERSITY OF PUERTO RICO AT HUMACAO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7793571
• 关键词: Address; Adverse effects; Agonist; Alcohol consumption; Alcohols; Alkylation; Amides; Amines; Amino Alcohols; Amphetamines; Antihistamines; Area; Benzazepines; Biological; Biomedical Research; Boron; Chemistry; Complex; Data; Development; Goals; Hydroxyl Radical; Imines; Investigation; Ketoximes; Knowledge; Lithium; Methodology; Methods; Modeling; Optics; Organic Chemistry; Oximes; Pharmaceutical Preparations; Pharmacologic Substance; Preparation; Property; Protocols documentation; Reaction; Reagent; Silicon; System; Work; base; carbonyl group; catalyst; design; enantiomer; novel; physical property; programs; silicon compounds

The preparation of chiral compounds in organic chemistry is an area of intense study due to the concern that many chiral drugs are consumed as racemic mixtures with the potential toxic side effects caused by the other enantiomer. In addition, chiral organic compounds are used as building blocks for the synthesis of many pharmaceutical products, and as auxiliaries in a vadety of enantioselective organic preparations. The main purpose of this project is to design new methodologies for the enantioselective synthesis of biological active compounds. Based on the expertise developed during the past years, work on the synthesis of enantio-pure primary phenylalkyl amines, and other amino derivatives v/a the reduction and alkylation of N-substituted organometallic (boron and silicon) imino derivatives will be our main objectives. We will continue with a detailed investigation of the scope and mechanisms involved in the achiral and enantioselective reductions of these synthons, since in addition to the development of primary amines, novel methodologies have been discovered for other important pharmaceutical compounds, such as hydroxyl amines and benzazepines. Preliminary resultson the synthesis of novel chiral aminoborohydrides and organoboranes reagents generated by the reaction of 1,3,2-oxazaborolidines with organolithiums, will be expanded for the enantioselective reduction of imine and/or carbonyl groups. These reagents offer a great potential for a variety of biomedical applications. The chemistry of O-silylated and O-borylated aromatic ketoximes will be further investigated for the synthesis of biological active heterocyclic amino compound and other dedvatives. In addition, based on the results of the o¿-alkylation and silylation of O-silylated oximes, we will explore the novel synthesis of 1,2- and 1,3-amino alcohols. The proposed synthetic strategies will be focused on the development of new methods for the preparation of homochiral compounds used as intermediaries or reagents for the synthesis of important pharmacological products.

有机化学中手性化合物的制备是一个深入研究的领域，因为担心 许多手性药物被消耗为外消毒混合物，其潜在的有毒副作用由另一种毒性造成 对映异构体。此外，手性有机化合物被用作合成许多的基础 制药产品，作为对映选择性有机制剂的辅助制品。 该项目的主要目的是为生物学的对映选择性合成设计新方法 活性化合物。基于过去几年发展的专业知识，从事对照芯的合成 原代苯基烷基胺和其他氨基衍生物V/A的n-取代有机物的还原和比对 （硼和硅）Imino衍生物将是我们的主要目标。我们将继续进行详细的调查 这些合成子的范围和机制涉及的范围和机制，因为 在原代胺的发展中，已经发现了其他重要的方法 药物化合物，例如羟基胺和苯唑汀。初步结果森的合成 手性氨基羟基氢氢化盐和有机菜烷试剂由1,3,2-氧化烷酚与与 有机锂将扩展，以减少亚胺和/或羰基的对映选择性减少。这些试剂 为各种生物医学应用提供了巨大的潜力。 O-硅胶和O-boryated芳香族的化学反应 Ketoximes将进一步研究生物活性杂环氨基化合物的合成和其他 泰思格。此外，根据O检测的O检测和硅胶化的结果，我们将探索 1,2-和1,3-氨基醇的新型合成。 拟议的合成策略将集中于制定新方法的开发 用于合成重要药品的中间体或试剂的同型化合物。