Department of Chemistry, BioScience Research Collaborative, Rice University, 6100 Main Street, Houston, Texas 77005, United States.
Texas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, 1881 East Road, Houston, Texas 77054, United States.
J Am Chem Soc. 2020 Nov 25;142(47):20201-20207. doi: 10.1021/jacs.0c10660. Epub 2020 Nov 13.
The architecturally symmetrical and synthetically challenging marine natural products lomaiviticins A and B present alluring synthetic targets due to their molecular complexity, potent antitumor properties, and natural scarcity. Herein, we report the total synthesis of the fully glycosylated monomeric unit of lomaiviticin A, monolomaiviticin A. The retrosynthetically derived synthetic strategy relied on an intramolecular palladium-catalyzed coupling reaction to complete the tetracyclic aglycon scaffold and gold-promoted glycosylations to install the synthetically challenging α- and β-glycoside moieties of the target molecule. This accomplishment paves a path for the eventual total synthesis of lomaiviticins A and B and opens opportunities for biological investigations within this family of compounds.
由于其分子复杂性、强效抗肿瘤特性和天然稀缺性，具有建筑学对称和综合挑战性的海洋天然产物洛马维丁 A 和 B 成为了极具吸引力的合成目标。在此，我们报告了洛马维丁 A 的完全糖基化单体单元单洛马维丁 A 的全合成。该反合成推导的合成策略依赖于钯催化的分子内偶联反应来完成四环骨架，并通过金促进的糖苷化反应来引入目标分子中具有挑战性的 α-和 β-糖苷部分。这一成就为洛马维丁 A 和 B 的最终全合成铺平了道路，并为该化合物家族的生物学研究开辟了机会。
