Synthesis of Pyrrole-Imidazole Alkaloids

吡咯咪唑生物碱的合成

• 批准号: 7494188
• 负责人: PHIL S BARAN
• 金额: $ 13.98万
• 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/7494188
• 关键词: Acids; Alkaloids; Alzheimer' s Disease; Antiviral Agents; Biological; Biological Factors; Biology; Biomimetics; Chemicals; Chemistry; Class; Collaborations; Complex; Cyclobutanes; Cystic Fibrosis; DNA Sequence Rearrangement; Development; E 10; Esters; Family; Imidazole; Institutes; Malignant Neoplasms; Marines; Medicine; Neuropharmacology; Palau; Palau' amine; Physiology; Porifera; Pyrroles; Reaction; Reporting; Research; Structure-Activity Relationship; Therapeutic Agents; Universities; Viral; analog; antineoplastic antibiotics; bromosceptrin; cancer research center director; chemical synthesis; debromosceptrin; dibromosceptrin; improved; massadine; medical schools; member; oxysceptrin; professor; sceptrin

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).

海军陆战队的一些最有前途的铅是强大的治疗剂 海绵。除了为这些化合物提供环保的途径，化学 综合能够开发具有提高生物活性的类似物，并定期导致 化学，生物学和医学的基本发现。吡咯 - 咪唑生物碱是一个 多元化的海洋海绵家族衍生出具有生物活性的天然产品，包括： 抗生素，抗生素，抗病毒，抗疗养者，抗毒性和潜在铅的囊性纤维化铅 和阿尔茨海默氏病。该提议涵盖了化学和生物学方面 该天然产品类别的几个成员，包括其最复杂的成员。因此， 权杖，氧化剂，含核酸，杏仁素，nagelamide，nagelamide的对映选择性合成 提出了Axinellamine，Massadine和Palau'amine。总体目的是提供有用的 这些天然产物的数量使用简洁的合成序列和仿生级联 反应。在实现这些化合物的实际合成后，我们将研究它们的结构 活动关系和行动机理通过合作。生物学研究将是 与癌症领域的领导人合作进行（鲍勃·亚伯拉罕教授，伯纳姆 Institute），病毒（埃默里（Emory）雷蒙德·辛纳齐（Raymond Schinazi）教授），神经药理学（乔治教授 Siggins，Scripps）和生理学（Lee Sweeny博士，宾夕法尼亚州医学中心）。