Synthesis of Pyrrole-Imidazole Alkaloids

吡咯咪唑生物碱的合成

• 批准号: 8267033
• 负责人: PHIL S BARAN
• 金额: $ 43.91万
• 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 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8267033
• 关键词: Alkaloids; Antiviral Agents; Architecture; Biogenesis; Biological; Biological Factors; Chemicals; Chemistry; Collaborations; Complex; Family; Family member; Future; Hawaii; Illinois; Imidazole; Immunosuppressive Agents; Indoles; Institutes; Investigation; London; Medical Research; Medicine; Methodology; Methods; Property; Pyrroles; Research; Silver; Universities; abstracting; analog; antineoplastic antibiotics; cell motility; chemical synthesis; college; innovation; interest; marine natural product; member; novel; oxidation; professor; public health relevance; scaffold; small molecule

DESCRIPTION (provided by applicant): Abstract It is undeniable that a majority of small molecule medicinal agents are natural products or are inspired by natural product scaffolds. Total synthesis greatly contributes to this arena via the procurement of natural products (and analogs) and the creation of new methodologies to enable future syntheses. The pyrrole-imidazole class of natural products possesses a wealth of bioactivities including antitumor, antibiotic, antihistaminic, antiviral, immunosuppressant and cell-motility inhibition. Additionally, the complex architectures of the polycyclic members of this natural product family instigate the creation of new chemical methods. This proposal encompasses the chemical syntheses of the remaining members of this class, the elaboration of a novel silver(II)- oxidation methodology, and numerous collaborative efforts to extensively investigate the biogenesis and structural intricacies of these molecules. Research will also be conducted on a new class of dimeric marine natural products: the indole-imidazole alkaloids. This class possesses interesting architectural parallels to the pyrrole-imidazole alkaloids, and can serve as a similar platform for the invention of chemical methods and investigation of biological properties. The breadth of research proposed herein is enabled by an extensive collaboration network that includes Pfizer, Professor Donna Blackmond (Imperial College London), Professor Matthias Kvck (Alfred-Wegener-Institut f|r Polar- und Meeresforschung), Professor Philip Williams (University of Hawaii at Manoa), Professor Paul Hergenrother (University of Illinois), and Professor Angel Cipres (Burnham Institute for Medical Research). PUBLIC HEALTH RELEVANCE: Project Narrative This proposal aims at using chemical synthesis to prepare several natural products (and analogs thereof) of the pyrrole-imidazole and indole-imidazole alkaloid families. Innovations in chemistry are anticipated and substantial contributions to medicine may result through several strategic collaborative efforts with a variety of experts in related fields.

描述（由申请人提供）：摘要是不可否认的是，大多数小分子药物都是天然产物或受到天然产品支架的启发。通过自然产品（和类似物）的采购以及创建新方法，以实现未来的合成，从而极大地促进了该领域。吡咯 - 咪唑类天然产物具有丰富的生物活性，包括抗肿瘤，抗生素，抗组胺药，抗病毒，免疫抑制剂和细胞运动抑制。此外，该天然产物家族的多环切成员的复杂体系结构激发了新的化学方法的创建。该建议涵盖了该类别其余成员的化学合成，新型银（II） - 氧化方法的阐述以及许多协作努力，以广泛研究这些分子的生物发生和结构复杂性。还将对新的一类二聚体海洋天然产品进行研究：吲哚 - 咪唑生物碱。该类别具有与吡咯并咪唑生物碱相似的有趣的建筑相似之处，并且可以作为化学方法发明和生物学特性研究的类似平台。 The breadth of research proposed herein is enabled by an extensive collaboration network that includes Pfizer, Professor Donna Blackmond (Imperial College London), Professor Matthias Kvck (Alfred-Wegener-Institut f|r Polar- und Meeresforschung), Professor Philip Williams (University of Hawaii at Manoa), Professor Paul Hergenrother (University of Illinois), and Professor Angel Cipres (Burnham Institute用于医学研究）。 公共卫生相关性：项目叙事该提案旨在使用化学合成来准备吡咯氨基唑和吲哚 - 咪唑生物碱家庭的几种天然产品（及其类似物）。预计化学的创新是通过与相关领域的各种专家进行的几项战略合作努力来对医学产生的实质性贡献。