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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(申请人提供)：建议的研究包括开发利用铜催化的醛、酮和亚胺的二硼化合成方法。由此得到的？-杂原子取代的硼酸酯具有已知的药用性能和在靶向合成中的潜在应用。拟议方法的一个优点是提供了新的氨基硼酸酯和酸、已知的丝氨酸蛋白酶抑制剂和Bortezomib(VELCADE)的基本成分，Bortezomib是FDA批准的治疗多发性骨髓瘤的药物。拟议的合成方法将简化获得额外的？-杂原子取代的硼酸酯的途径，这些化合物可用于追求新的药物靶标，具有更高的效力和未实现的医学应用。概述的研究计划的目标是开发羰基化合物和亚胺的二硼化反应，并开发合成产物的合成用途，用于定向合成。为了实现这一目标，该研究计划的具体目标包括：1)建立促进醛、酮和亚胺二硼反应的一般反应条件。2)利用手性二硼试剂或手性配体开发不对称双硼反应条件。3)开发涉及二硼产物的合成应用，包括Matteson类型的同系化反应和支化的乙烯基硼酸酯的形成。与公共健康相关：C-B键的合成多功能性已导致其用于合成无数天然产品和药物靶标。将硼取代基结合到有机底物中的新方法将增加通过这些转化可以获得的分子类型。拟议的研究计划涉及在铜催化下的羰基化合物和亚胺的二硼化反应，以及将所得产物开发为有机合成中可合成的中间体。