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: 7598952
• 负责人: MARGARITA ORTIZ-MARCIALES
• 金额: $ 13.05万
• 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/7598952
• 关键词: Address; Adverse effects; Agonist; Alcohol consumption; Alcohols; Alkylation; Amides; Amines; Amino Alcohols; Amphetamines; Antihistamines; Area; Benzazepines; Biological; Boron; Chemistry; Complex; Condition; Data; Development; Goals; Hydroxyl Radical; Imines; Inorganic Silicon Compounds; Investigation; Ketoximes; Knowledge; Lithium; Methodology; Methods; Modeling; Object Attachment; Optics; Organic Chemistry; Oximes; Pharmaceutical Preparations; Pharmacologic Substance; Preparation; Property; Protocols documentation; Purpose; Reaction; Reagent; Silicon; System; Work; base; carbonyl group; catalyst; design; enantiomer; novel; physical property; 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，因为人们担心 许多手性药物作为外消旋混合物消耗，具有由其他药物引起的潜在毒副作用 对映体。此外，手性有机化合物被用作合成许多化合物的结构单元。 医药产品，以及作为多种对映选择性有机制剂中的助剂。 该项目的主要目的是设计生物对映选择性合成的新方法 活性化合物。基于过去几年开发的专业知识，致力于对映体纯的合成 苯烷基伯胺和其他氨基衍生物 v/a N-取代有机金属的还原和烷基化 （硼和硅）亚氨基衍生物将是我们的主要目标。我们将继续进行详细调查 这些合成子的非手性和对映选择性还原所涉及的范围和机制，因为 除了伯胺的开发之外，还发现了其他重要的新方法 药物化合物，例如羟胺和苯并氮杂卓。新型合成的初步结果 1,3,2-恶唑硼烷与手性氨基硼氢化物和有机硼烷试剂反应生成 有机锂将被扩展用于亚胺和/或羰基的对映选择性还原。这些试剂 为各种生物医学应用提供了巨大的潜力。 O-甲硅烷基化和O-硼基化芳族化合物的化学 将进一步研究酮肟用于合成生物活性杂环氨基化合物等 衍生物。此外，基于O-甲硅烷基化肟的O¿烷基化和甲硅烷基化结果，我们将探索 1,2-和1,3-氨基醇的新合成。 所提出的合成策略将侧重于开发制备 用作合成重要药理产品的中间体或试剂的纯手性化合物。