STEREOCHEMICAL CONTROLLED SYNTHESIS OF BIOLOGICALLY ACTIVE AMINES

有机手性化合物制备新技术 化学是一个高度发展的领域，因为人们担心 许多手性药物作为外消旋混合物被消费，具有潜在的 另一种对映体引起的毒性作用。手性胺、氨基 醇和氨基酸是重要的有机化合物，用作 用于合成许多医药产品的积木，以及 各种对映体选择性有机制剂中的助剂。 对映体选择性合成新方法的设计 具有生物活性的对映体化合物将是主要用途 这个项目的。通过我们以前的研究工作，我们已经开发出 一次苯基烷胺合成新工艺 通过N-取代有机金属的还原获得良好的光学纯度 使用已知手性有机硼烷试剂的亚氨基衍生物。目前， 我们设想将开发的方法应用于 胺和氨基醇的制备。此外，该化合物的合成 α去质子法合成的新型手性氨基硼氢化物 手性胺-硼烷与n-BuLi或LDA的络合物还原反应 将提出亚胺和/或羰基。这些试剂提供了 更高的反应性和更好的立体化学控制 不存在竞争性还原物种。具有代表性的前手性 亚胺和芳香酮亚胺将被所提议的手性化合物还原。 不同反应条件下试剂及其对映体选择性的研究 条件。基于O-TBS的α-烷基化反应结果 苯乙酮肟的不对称诱导制备非 外消旋产物将尝试使用手性酰胺作为碱，或者 手性催化剂，如1，3，2-恶唑硼烷。手性 酸性α-质子对外消旋伯胺的去质子化 从这一新领域开始，将对苄基位置和氨基酸进行研究 为生物活性化合物的制备提供了重要的参考价值。 拟议的综合战略将集中在以下方面的发展 新型手性化合物的制备新方法 合成重要化合物的中间体试剂 药理产品。

New technology for the preparation of chiral compounds in organic chemistry is an area of intense developments, due to the concern that many chiral drugs are consumed as racemic mixtures with the potential toxic effects caused by the other enantiomer. Chiral amines, amino alcohols and amino acids are important organic compounds used as building blocks for the synthesis of many pharmaceutical products, and auxiliaries in a variety of enantioselective organic preparations. The design of new methodologies for the enantioselective synthesis of enantiopure compounds with biological activity will be the main purpose of this project. Through our previous research work, we have developed new procedures for primary phenylalkylamine synthesis with modest to good optical purity via the reduction of N-substituted organometallic imino derivatives using known chiral organoborane reagents. Presently, we envision the application of the developed methodology for the preparation of amines and amino alcohols. Besides, the synthesis of novel chiral aminoborohydrides generated by the alpha deprotonation of chiral amine-borane complexes with n-BuLi or LDA for the reduction of imine and/or carbonyl groups, will be proposed. These reagents offer higher reactivity and a better stereochemical control since other competing reducing species are not present. Representative pro-chiral imines and aromatic ketoimines will be reduced with the proposed chiral agents and their enantioselectivity studied under various reaction conditions. Based on the results of the alpha-alkylation of O-TBS acetophenone oximes, asymmetric induction for the preparation of non- racemic products will be attempted using chiral amides as bases, or chiral catalysts, such as 1,3,2-oxazaborolidines. The chiral deprotonation of racemic primary amines with acidic alpha-protons at benzylic positions and amino acids, will be studied since this new area offer great value for the preparation of biological active compounds. The proposed synthetic strategies will be focused on the development of new methods for the preparations of homochiral compounds used as intermediaries of reagents for the synthesis of important pharmacological products.