中国海洋大学药学院李明研究组在研究中取得进展。他们的最新研究提出了一种高效和模块化的方法来合成龙霉素A-C及其类似物。相关论文于2025年2月11日发表于国际顶尖学术期刊《Chinese Journal of Chemistry》杂志上。

该课题组人员在此描述了一种高效和模块化的方法来合成龙霉素A-C及其类似物，以市售的廉价的大霉素和d -核糖基巯基糖苷衍生物为起始原料。它们合成的一个关键特征是构建了不常见的三氧三环[6.2.1]十一烷骨架。这种具有挑战性的结构是通过立体控制β-核呋喃烷键的形成和DDQ（2,3-二氯-5,6-二氰-1,4-苯醌）在苯基位置促进分子内交叉脱氢醚化来实现的。它们的合成的另一个特点是在叔碳-4'上成功地安装了一个氯原子和一个甲氧基；通过后期银催化的脱羧氯化反应和烯醇中间体的亲电醚化反应来定位。对合成的化合物进行细胞毒性评价，发现龙毒素A的n -去甲基化衍生物去甲基龙毒素A对A549肺癌、HCT116结直肠癌和MCF7乳腺癌具有很强的细胞毒性，是潜在的抗癌候选物质。本研究也初步证明了该化合物的构效关系，为开发新型抗癌候选物质奠定了坚实的基础。

研究人员表示，Dragocins A-C是一种结构独特的海洋天然产物，具有罕见的三氧三环[6.2.1]十一烷部分。然而，它们极低的天然丰度阻碍了对其生物活性的广泛筛选。

附：英文原文

Title: Modular Synthesis and Cytotoxicity Evaluation of Dragocins A—C and Their Analogues: Discovery of a Potential Anticancer Agent

Author: Ziqiang Wang, Jianjun Wang, Peng Wang, Ni Song, Xue-Wei Liu, Ming Li

Issue&Volume: 2025-02-11

Abstract: Dragocins A—C are structurally unique marine natural products featuring an uncommon tri-oxa-tricyclic[6.2.1]undecane moiety. However, their extremely low natural abundance has hindered extensive screening of their bioactivities. We hereby describe an efficient and modular approach to synthesizing dragocins A—C and their analogues using commercially available and inexpensive anisomycin and D-ribosyl thioglycoside derivative as the starting materials. A key feature of our synthesis is the construction of the uncommon tri-oxa-tricyclic[6.2.1]undecane skeleton. This challenging architecture is achieved by the stereocontrolled formation of the β-ribofuranosidic bond and the DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone)-promoted intramolecular cross-dehydrogenative etherification at the benzylic position. Our synthesis is also characterized by the successful installation of a chlorine atom and a methoxy group at the tertiary C-4' position via a late-stage silver-catalyzed decarboxylative chlorination reaction and an electrophilic etherification reaction of the enol intermediate. Cytotoxicity evaluations of the synthesized compounds revealed demethyl dragocin A, the N-demethylated derivative of dragocin A, as a potential anticancer candidate due to its strong cytotoxicity against A549 lung, HCT116 colorectal and MCF7 breast cancer cell lines. This work also demonstrated the preliminary structure-activity relationship of this compound, setting a solid foundation for developing novel anticancer candidates.

DOI: 10.1002/cjoc.202401236

Source: https://onlinelibrary.wiley.com/doi/full/10.1002/cjoc.202401236