New Methodologies for the Synthesis of Biologically Active Amino Derivatives

在有机化学中，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被消费，其潜在的毒副作用由另一种药物引起。 对映体。此外，手性有机化合物被用作合成许多 医药产品，以及作为各种对映体选择性有机制剂的辅助剂。 本项目的主要目的是设计用于生物对映体选择性合成的新方法。 活性化合物。基于过去几年发展起来的专业知识，合成对映体纯品的工作 伯苯基烷基胺及其他氨基衍生物N-取代有机金属的还原和烷基化反应 (硼和硅)亚胺基衍生物将是我们的主要目标。我们将继续进行详细的调查 这些合成子的非手性和对映体选择性还原所涉及的范围和机制，自 除了伯胺的开发外，还发现了其他重要的 药物化合物，如羟胺和苯扎西平。长篇小说综合初见成效 1，3，2-恶唑硼烷与有机硼烷反应生成的手性氨基硼氢化物和有机硼烷试剂 有机硫化合物将被扩展，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-硅烷化和O-硼化芳香族的化学 酮肟类化合物在合成生物活性杂环氨基化合物等方面将得到进一步的研究 预言词。此外，基于O-硅烷基化和硅烷化的结果，我们还将探索 1，2-和1，3-氨基醇的新合成。 拟议的合成战略将侧重于开发新的制备方法 用作合成重要药理产品的中间体或试剂的同手性化合物。

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.