Total Synthesis of the Antitumor Agent Diazonamide A

抗肿瘤药物重氮酰胺A的全合成

• 批准号: 6885150
• 负责人: YOUNG K CHEN
• 金额: $ 5.35万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-08 至 2006-08-07
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6885150
• 关键词: Tunicata; antineoplastics; aquatic organism; biological products; biotherapeutic agent; catalyst; chemical synthesis; drug discovery /isolation; oxazoles; postdoctoral investigator

DESCRIPTION (provided by applicant): The objective of the proposed research is to develop an enantioselective total synthesis of diazonamide A. The natural product was isolated from the marine ascidian diazona chinensis, and possesses potent in vitro activity against HCT-116 human colon carcinoma and B-16 murine melanoma cancer cell lines with IC50 in the nanomolar range. The proposed research utilizes a novel organocatalysis strategy, developed in the MacMillan group, to generate the furolindoline core of diazonamide. Successful installation of the furolindoline core will serve as the platform for refining and developing new chemical methods to complete the bismacrocyclic framework of diazonamide A. An expeditious completion of the natural product will not only provide a synthetic sample, but also permits access to unnatural analogues for further biological evaluation.

描述（由申请人提供）： 本研究的目的是发展一种对映选择性全合成重氮酰胺A的方法。该天然产物分离自海洋海鞘重氮藻（ascidian diazona chinensis），并且具有针对HCT-116人结肠癌和B-16鼠黑素瘤癌细胞系的有效体外活性，IC 50在纳摩尔范围内。拟议的研究利用了一种新的有机催化策略，在麦克米伦集团开发，以产生diazonamide的呋喃并吲哚啉核心。呋喃并吲哚啉核的成功安装将成为精炼和开发新化学方法以完成重氮酰胺A的双大环骨架的平台。天然产物的快速完成将不仅提供合成样品，而且还允许获得非天然类似物用于进一步的生物学评价。