Synthesis of Pyrrole-Imidazole Alkaloids

吡咯咪唑生物碱的合成

• 批准号: 6908565
• 负责人: PHIL S BARAN
• 金额: $ 27.89万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6908565
• 关键词: Porifera; alkaloids; analog; aquatic organism; biological products; biomimetics; biotechnology; biotherapeutic agent; chemical reaction; chemical structure function; chemical synthesis; drug design /synthesis /production; drug discovery /isolation; imidazole; pharmacokinetics; pyrroles

DESCRIPTION (provided by applicant): Some of the most promising leads for powerful therapeutic agents have arisen from marine sponges. Aside from providing an environmentally friendly avenue to these compounds, chemical synthesis enables the development of analogs with improved bioactivity and regularly leads to fundamental discoveries in chemistry, biology and medicine. The pyrrole-imidazole alkaloids are a diverse family of marine sponge derived natural products with reported bioactivity including: anticancer, antibiotic, antiviral, antihistiminic, antimuscarinic and potential leads for cystic fibrosis and Alzheimer's disease. This proposal encompasses both the chemical and biological aspects of several members of this natural product class, including its most complex members. Thus, enantioselective syntheses of sceptrin, oxysceptrin, nakamuric acid, ageliferin, nagelamide, axinellamine, massadine, and palau'amine are proposed. The overall aim is to provide useful amounts of these natural products using concise synthetic sequences and biomimetic cascade reactions. Upon achieving practical syntheses of these compounds we will study their structure activity relationships and mechanism of action through collaborations. The biological studies will be carried out in collaboration with leaders in the fields of cancer (Professor Bob Abraham, Burnham Institute), viral (Professor Raymond Schinazi, Emory), neuropharmacology (Professor George Siggins, Scripps) and physiology (Dr. Lee Sweeny, Penn State Med. Center).

描述（由申请人提供）：有强大治疗剂的一些最有前途的铅来自海洋海绵。除了为这些化合物提供环境友好的途径外，化学综合还可以开发具有改善的生物活性的类似物，并定期导致化学，生物学和医学方面的基本发现。吡咯 - 咪唑生物碱是据报道的生物活性的多样化的海绵衍生的天然产物家族，包括：抗癌，抗生素，抗病毒，抗组织中心症，抗毒性，抗毒性和潜在铅的囊性纤维化和潜在铅，用于囊性纤维化和阿尔茨海默氏病。该提议涵盖了该天然产品类别的几个成员的化学和生物学方面，包括其最复杂的成员。因此，提出了对映选择性合成，氧化蛋白，氧蛋白酶，中尿酸，杏仁酸酯，nagelamide，nagelamide，xaxinellamine，massadine和palau'amine提出了对映选择性合成。总体目的是使用简洁的合成序列和仿生级联反应提供有用的这些天然产品。在实现这些化合物的实际合成后，我们将通过协作研究其结构活动关系和行动机理。生物学研究将与癌症领域的领导者（Bob Abraham，Burnham Institute），Viral（Raymond Schinazi，Emory教授），Neuropharmacology（George Siggins，Scripps）和生理学（Lee Sweeny，Penn State Med。中心）合作进行。