Laboratory of Organic Chemistry, Helsinki University of Technology, PO Box 6100, FIN-02015 HUT, Finland.
Mar Drugs. 2010 Jan 21;8(1):122-72. doi: 10.3390/md80100122.
Calyculins, highly cytotoxic polyketides, originally isolated from the marine sponge Discodermia calyx by Fusetani and co-workers, belong to the lithistid sponges group. These molecules have become interesting targets for cell biologists and synthetic organic chemists. The serine/threonine protein phosphatases play an essential role in the cellular signalling, metabolism, and cell cycle control. Calyculins express potent protein phosphatase 1 and 2A inhibitory activity, and have therefore become valuable tools for cellular biologists studying intracellular processes and their control by reversible phosphorylation. Calyculins might also play an important role in the development of several diseases such as cancer, neurodegenerative diseases, and type 2-diabetes mellitus. The fascinating structures of calyculins have inspired various groups of synthetic organic chemists to develop total syntheses of the most abundant calyculins A and C. However, with fifteen chiral centres, a cyano-capped tetraene unit, a phosphate-bearing spiroketal, an anti, anti, anti dipropionate segment, an alpha-chiral oxazole, and a trihydroxylated gamma-amino acid, calyculins reach versatility that only few natural products can surpass, and truly challenge modern chemists' asymmetric synthesis skills.
钙调神经磷酸酶抑制剂，最初是由 Fusetani 及其同事从海洋海绵 Discodermia calyx 中分离出来的高度细胞毒性多酮类化合物，属于石珊瑚海绵群。这些分子已成为细胞生物学家和合成有机化学家感兴趣的目标。丝氨酸/苏氨酸蛋白磷酸酶在细胞信号转导、代谢和细胞周期控制中发挥着重要作用。钙调神经磷酸酶抑制剂表达出强烈的蛋白磷酸酶 1 和 2A 抑制活性，因此已成为研究细胞内过程及其通过可逆磷酸化控制的细胞生物学家的宝贵工具。钙调神经磷酸酶抑制剂可能在癌症、神经退行性疾病和 2 型糖尿病等多种疾病的发展中发挥重要作用。钙调神经磷酸酶抑制剂迷人的结构激发了各种合成有机化学家团队开发最丰富的钙调神经磷酸酶 A 和 C 的全合成。然而，具有 15 个手性中心、一个氰基封端的四烯单元、一个带有磷酸基的螺缩酮、一个 anti, anti, anti 二丙酸酯片段、一个 alpha-手性恶唑和一个三羟基化的 gamma-氨基酸，钙调神经磷酸酶抑制剂的多功能性只有少数天然产物才能超越，并真正挑战现代化学家的不对称合成技能。
