STEREOCHEMICAL CONTROLLED SYNTHESIS OF BIOLOGICALLY ACTIVE AMINES

有机溶剂中制备手性化合物的新技术 化学是一个激烈的发展领域，由于关注， 许多手性药物作为外消旋混合物被消耗， 其他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， 用于合成许多药物产品的结构单元，以及 在各种对映体选择性有机制剂中的助剂。 对映选择性合成的新方法学设计 具有生物活性的对映体纯化合物将是主要目的 of this project项目.通过我们以前的研究工作，我们开发了 合成伯苯基烷基胺的新方法， 通过N-取代的有机金属的还原获得良好的光学纯度 使用已知的手性有机硼烷试剂的亚氨基衍生物。目前， 我们设想将所开发的方法应用于 胺和氨基醇的制备。此外， 通过α-去质子化产生的新的手性氨基硼烷， 具有n-BuLi或LDA的手性胺-硼烷络合物用于还原 亚胺和/或羰基。这些试剂提供 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。代表性前手性 亚胺和芳香酮亚胺将被还原与建议的手性 试剂及其在不同反应条件下的对映选择性 条件基于O-TBS的α-烷基化结果， 苯乙酮肟，不对称诱导制备非 将尝试使用手性酰胺作为碱制备外消旋产物，或 手性催化剂，例如1，3，2-恶唑硼烷。手性 外消旋伯胺与酸性α-质子的去质子化 苄基位置和氨基酸，将研究，因为这个新的领域 对生物活性化合物的制备具有重要价值。 拟议的合成战略将集中于开发 制备用作手性化合物的新方法 重要合成试剂的中间体 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.