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.

手性化合物的制备在有机化学中是一个激烈的研究领域，因为人们担心， 许多手性药物作为外消旋混合物被消耗， 对映体。此外，手性有机化合物被用作合成许多手性化合物的结构单元。 医药产品，以及在多种对映体选择性有机制剂中作为助剂。 本项目的主要目的是设计新的方法学来对映选择性地合成生物活性化合物 活性化合物根据过去几年发展的专门知识， 伯苯基烷基胺和其他氨基衍生物v/a N-取代的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。我们会继续详细调查 的范围和机制，参与非手性和对映体选择性减少这些candrons，因为在 除了开发伯胺之外，还发现了用于其他重要的合成的新方法。 药物化合物，如羟胺和苯并氮杂。合成新的 通过1，3，2-恶唑硼烷与 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-硼基化芳烃的化学 酮肟类化合物在合成具有生物活性的杂环氨基化合物及其它生物活性化合物方面具有广阔的应用前景。 派生词此外，基于O-硅烷基化肟的O-烷基化和硅烷基化的结果，我们将探索 1，2-和1，3-氨基醇的新合成方法。 所提出的合成策略将集中于开发用于制备 用作合成重要药物产品的中间体或试剂的纯手性化合物。