Total Synthesis of Antitumor Agent, Deoxyverrucosidin

描述(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，可以更快、更有效地制备药物候选，这是药物发现所必需的。这项建议研究了一类用于合成的新型空气稳定构建块。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另外两个片段。这一方法将在新型抗肿瘤药物脱氧疣芦丁的全合成中得到证明。脱氧马鞭草苷强烈抑制葡萄糖调节蛋白78(GRP78)，GRP78是一种(在体外)已知在实体肿瘤保护和运输中发挥作用的蛋白质。这可能会使更温和的抗癌药物得以实施，因为这种自然产生的化合物抑制了防御机制和运输方式。这种合成的一般性应该为进一步的生物学研究提供目标，以及开发新的类似物来微调其抗肿瘤特性。

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.