Asymmetric Synthesis of Biologically Active Materials

生物活性材料的不对称合成

• 批准号: 6656876
• 负责人: SCOTT G. NELSON
• 金额: $ 18.46万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6656876
• 关键词: antineoplastics; antiviral agents; chemical bond; chemical synthesis; cyclic peptides; drug design /synthesis /production; inhibitor /antagonist; integrins; organic chemicals; stereochemistry

DESCRIPTION: (Applicant's Description) Our principle goal during the tenure of this grant will be the development of new catalyzed organic reactions for the stereospecific assemblage of C-C bond with broad, applications to the synthesis of a variety of target compounds possessing pharmacological activity. The reaction technology under development is specifically designed to address fundamental C-C bond forming reactions that are generally applicable to complex molecule synthesis and the preparation of important chemical building blocks in the context of industrial or medicinal chemistry synthesis activities. Catalyzed asymmetric acyl chloride-aldehyde cyclocondensations developed in our laboratories are further developed as versatile reaction technology for asymmetric organic synthesis. This methodology will be refined and developed in the context of the total synthesis of naturally occurring materials that express potent anticancer and antiviral activities, including amphidinolide B, rhazinilam, and motuporin. Moreover, a family of unique optically active Al(III)-based Lewis acids will be developed as bifunctional Lewis acidic-Lewis basic catalysts with applications to a variety of asymmetric C-C bond constructions. An economical and operationally simple synthesis of highly enantiomerically enriched beta-amino acids is also exploited in an efficient approach to the synthesis of beta-peptides and the preparation of cyclic beta-peptide structures designed to function as integrin receptor antagonists.

描述：（申请人的描述）我们在这笔赠款任期期间的主要目标是开发新的催化有机反应 C-C键的立体特异性组合，范围广泛的合成应用 具有药理活性的多种靶化合物。这 正在开发的反应技术专门设计用于解决 基本的C-C键形成通常适用于复杂的反应 分子合成和重要的化学构建块的制备 工业或药物化学合成活动的背景。 在我们的 实验室进一步发展为多功能反应技术 不对称有机合成。该方法将在 自然存在的材料的总合成的背景 表达有效的抗癌和抗病毒活性，包括两栖动物B， Rhazinilam和Motuporin。而且，一个独特的光学活动家族 基于Al（III）的刘易斯酸将作为双功能刘易斯酸性刘易斯开发 基本催化剂，并应用于各种不对称的C-C键 构造。经济和操作的简单合成 在有效的 β肽合成和循环制备的方法 旨在充当整联蛋白受体拮抗剂的β-肽结构。