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）： 拟议的研究的目的是开发重18zonamideA的对映选择性的总合成。从海洋海藻二氧化圆角中分离出天然产物，并具有针对HCT-116人类结肠癌和B-16鼠类黑色素瘤癌细胞的IC50的IC50的HCT-116人类结肠癌的体外活性。拟议的研究采用了Macmillan组开发的一种新型的有机催化策略来产生重18zonamide的Furolindoline核心。成功安装Furolindoline Core将是精炼和开发新的化学方法的平台，以完成重射氨酰胺A的二脑环框架A。天然产品的迅速完成不仅将提供合成样本，而且还允许访问不自然的类似物进行进一步的生物学评估。