SYNTHESIS OF BIOLOGICAL ACTIVE AMINES, AMINOALCOHOLS

生物活性胺、氨基醇的合成

• 批准号: 2885793
• 负责人: MARGARITA ORTIZ-MARCIALES
• 金额: $ 11.44万
• 依托单位: UNIVERSITY OF PUERTO RICO AT HUMACAO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2003-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2885793
• 关键词: amines; aminoalcohol; boranes; chemical synthesis; imines; phenylalkylamine; protonation; stereoisomer

DESCRIPTION: (Applicant's Abstract) 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 aimine-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 prochiral 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 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.

描述：（申请人摘要）制备 有机化学中的手性化合物是一个快速发展的领域，由于 担心许多手性药物作为外消旋混合物被消耗 另一种对映体引起的潜在毒性作用。手性胺、氨基 醇和氨基酸是用作建筑的重要有机化合物 用于合成许多医药产品和助剂的区块 各种对映选择性有机制剂。 对映选择性合成新方法的设计 具有生物活性的对映体纯化合物将是本次研究的主要目的 项目。通过之前的研究工作，我们开发了新的程序 用于合成具有中等至良好光学纯度的伯苯烷基胺 使用已知的方法还原N-取代的有机金属亚氨基衍生物 手性有机硼烷试剂。目前，我们设想应用 开发了胺和氨基醇的制备方法。 此外，通过合成产生的新型手性氨基硼氢化物 手性胺-硼烷配合物与 n-BuLi 或 LDA 的 α-去质子化 将建议减少亚胺和/或羰基。这些试剂 与其他产品相比，提供更高的反应活性和更好的立体化学控制 不存在竞争性还原物质。代表性的前手性亚胺和 芳香酮亚胺将被所提出的手性试剂及其 在不同反应条件下研究对映选择性。基于 O-TBS 苯乙酮肟的 α-烷基化结果，不对称 将尝试使用诱导来制备非外消旋产物 作为碱的手性酰胺，或手性催化剂，例如1,3,2-恶唑硼烷。 拟议的合成策略将侧重于开发新的 用作中间体的纯手性化合物的制备方法或 用于合成重要药理产品的试剂。