Calyculins and Related Marine Natural Products as Serine-Threonine Protein Phosphatase PP1 and PP2A Inhibitors and Total Syntheses of Calyculin A, B, and C

Annika E. Fagerholm, Damien Habrant, Ari M.P. Koskinen

    Research output: Contribution to journalArticleScientificpeer-review

    45 Citations (Scopus)
    148 Downloads (Pure)

    Abstract

    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 α-chiral oxazole, and a trihydroxylated γ-amino acid, calyculins reach versatility that only few natural products can surpass, and truly
    challenge modern chemists’ asymmetric synthesis skills.
    Original languageEnglish
    Pages (from-to)122-172
    JournalMARINE DRUGS
    Volume8
    Issue number1
    Publication statusPublished - 2010
    MoE publication typeA1 Journal article-refereed

    Keywords

    • Total Synthesis
    • marine natural products
    • protein phosphatase inhibitors

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