Total Synthesis of Antitumor Agent Eupenifeldin

抗肿瘤药Eupenifeldin的全合成

• 批准号: 6825359
• 负责人: DANNY NG
• 金额: $ 4.11万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6825359
• 关键词: antineoplastics; biological products; chemical synthesis; cycloheptanes; postdoctoral investigator; pyrans; stereoisomer

DESCRIPTION (provided by applicant): Nature is an important souce of various types of antitumor compounds. Recently a novel cytotoxic bistropolone Eupenifeldin was isolated from a culture broth produced by Eupenicillium brefeldianum ATCC 74184. Preliminary testing shows that Eupenifeldin is highly toxic in vitro against HCT-116 and HCT-VM4(human colon carcinoma) cell lines, with IC50 values of 5 ng/ml and 2 ng/ml, respectively. The following proposal describes a highly convergent and enantioselective total synthesis of the title compound. The key steps include the simultaneous introduction of both tropolone units to the eleven-membered core, as well as the stereoselective formation of both dihydropyran rings in a single step. If successful, the proposed route will provide large amount of the natural prouct for further biological evaluation, as well as the possibility to prepare other non-natural analogues for structure-activity relationship studies.

描述（由申请人提供）：自然界是各种类型抗肿瘤化合物的重要来源。最近，一种新的细胞毒性bistropolone Eupenifeldin从Eupenicillium brefeldianum ATCC 74184产生的培养液中分离。初步测试显示，在体外，Eupenifeldin对HCT-116和HCT-VM 4（人结肠癌）细胞系具有高毒性，IC 50值分别为5 ng/ml和2 ng/ml。以下建议描述了标题化合物的高度收敛和对映选择性的全合成。关键步骤包括同时引入两个环庚三烯酚酮单元的十一元核心，以及两个二氢吡喃环的立体选择性形成在一个单一的步骤。如果成功，该路线将为进一步的生物学评价提供大量的天然产物，以及制备其他非天然类似物用于构效关系研究的可能性。