Total Synthesis of Antitumor Agent, Deoxyverrucosidin

抗肿瘤剂脱氧verrucosidin的全合成

• 批准号: 7154435
• 负责人: BRYAN A FRIEMAN
• 金额: $ 4.4万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7154435
• 关键词: antineoplastics; biological products; glucose; method development; motivation; neoplasm /cancer; neoplastic growth; play; proteins; role; training

DESCRIPTION (provided by applicant): The discovery and development of new methods for the synthesis of tomorrow's cancer drugs is a crucial component of medicinal research. With the development of new methods, drug candidates can be prepared in a more rapid and efficient manner, necessary for drug discovery. This proposal investigates a new class of air-stable building blocks for use in synthesis. A key building block will function as a "linchpin", selectively joining two other segments of the target molecule. This approach will be demonstrated in the total synthesis of the novel antitumor agent, deoxyverrucosidin. Deoxyverrucosidin strongly inhibits glucose-regulated protein 78 (GRP78), a protein known (in vitro) to play a role in the protection and transport of solid tumors. This may allow milder anti-cancer drugs to be implemented since the defense mechanism and mode of transport are inhibited by this naturally occurring compound. The generality of this synthesis should provide both the target for further biological studies, as well as development of new analogs for fine-tuning its antitumor properties.

描述（由申请人提供）：发现和开发合成未来抗癌药物的新方法是医学研究的重要组成部分。随着新方法的发展，可以以更快速、更有效的方式制备候选药物，这是药物发现所必需的。该提案研究了用于合成的新型空气稳定结构单元。关键构建块将充当“关键”，选择性地连接目标分子的其他两个片段。这种方法将在新型抗肿瘤剂脱氧verrucosidin的全合成中得到证实。 Deoxyverrucosidin 强烈抑制葡萄糖调节蛋白 78 (GRP78)，这是一种已知（体外）在实体瘤的保护和转运中发挥作用的蛋白质。由于这种天然存在的化合物抑制了防御机制和运输方式，因此这可能允许使用更温和的抗癌药物。这种合成的普遍性应该为进一步的生物学研究以及开发新的类似物以微调其抗肿瘤特性提供目标。