Total Synthesis of Antitumor Agent, Deoxyverrucosidin

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，候选药物可以更快速、更有效地制备，这是药物发现所必需的。本提案研究了一类用于合成的新型空气稳定构件。一个关键的构建块将起到“关键”的作用，选择性地连接目标分子的其他两个片段。这种方法将被证明在全合成的新型抗肿瘤药物，去氧疣胞苷。Deoxyverrucosidin强烈抑制葡萄糖调节蛋白78 (GRP78)， GRP78是一种已知的（体外）在实体瘤的保护和运输中起作用的蛋白质。由于防御机制和运输方式被这种天然存在的化合物所抑制，这可能使更温和的抗癌药物得以实施。这种合成的普遍性为进一步的生物学研究提供了靶点，同时也为开发新的类似物来微调其抗肿瘤特性提供了依据。

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.