Developing the Synthetic Utility of the Copper-Catalyzed Diboration of Aldehydes

铜催化醛二硼化合成应用的开发

基本信息

批准号：
8295248
负责人：
Timothy B Clark
金额：
$ 35.34万
依托单位：
UNIVERSITY OF SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2013-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8295248
关键词：
Developing Synthetic Utility Copper Catalyzed

项目摘要

DESCRIPTION (provided by applicant): The proposed research involves the development of synthetic methods that utilizes the copper-catalyzed diboration of aldehydes, ketones, and imines. The resulting ?-heteroatom- substituted boronate esters have known pharmaceutical properties and potential applications in target-directed synthesis. One advantage of the proposed methodology is to provide access to new -aminoboronate esters and acids, known serine protease inhibitors and an essential component of Bortezomib (Velcade), an FDA-approved treatment of multiple myeloma. The proposed synthetic methodology would simplify access to additional ?-heteroatom-substituted boronate esters that could be used in the pursuit of new pharmaceutical targets with increased potency and unrealized medicinal applications. The objective of the outlined research plan is to develop the diboration of carbonyl compounds and imines and to exploit the synthetic utility of the resulting products for target- directed synthesis. To achieve this goal, the specific aims of the research plan include: 1) Establish general reaction conditions that mediate the diboration of aldehydes, ketones, and imines. 2) Develop asymmetric diboration reaction conditions using chiral diboron reagents or chiral ligands. 3) Develop synthetic applications involving the diboration products including Matteson-type homologation reactions and formation of branched vinyl boronate esters. PUBLIC HEALTH RELEVANCE: The synthetic versatility of the C-B bond has led to its use in the synthesis of countless natural products and pharmaceutical targets. New methods to incorporate boron substituents into organic substrates would increase the types of molecules that could be accessed through these transformations. The proposed research plan involves the copper-catalyzed diboration of carbonyl compounds and imines, and the development of the resulting products into synthetically viable intermediates in organic synthesis.

描述（由申请人提供）：拟议的研究涉及利用醛，酮和亚胺的铜催化含量的合成方法的发展。由此产生的？ - 近原子替代的硼酸酯具有已知的药物特性和潜在的指导合成中的应用。所提出的方法的一个优点是提供新的 - 氨基碳酸盐酸酯和酸，已知的丝氨酸蛋白酶抑制剂以及Bortezomib（Velcade）（Velcade）的必不可少的成分，这是多发性骨髓瘤的FDA批准治疗。拟议的合成方法将简化访问其他？ - 杂摩植物取代的硼酸酯酯，可用于追求新的药物靶标，并增加效力和未实现的药用应用。概述的研究计划的目的是开发羰基化合物和亚胺的无碎片，并利用所得产品的合成实用性用于靶标合成。为了实现这一目标，研究计划的具体目的包括：1）建立介导醛，酮和亚胺的尿的一般反应条件。 2）使用手性Diboron试剂或手性配体发展不对称的无动反应条件。 3）开发涉及无动产物的合成应用，包括麦芽剂型的同源反应和分支乙烯基硼酸酯的形成。公共卫生相关性：C-B键的合成多功能性导致其在无数天然产品和药物目标的合成中使用。将硼取代基合并到有机底物中的新方法将增加可以通过这些转换访问的分子的类型。拟议的研究计划涉及羰基化合物和亚胺的铜催化无解，以及在有机合成中将所得产物开发为合成可行的中间体。