Total Synthesis of 11-Saxitoxinethanoic Acid and Evaluation of its Inhibitory Activity on Voltage-Gated Sodium Channels

Chao Wang, Mana Oki, Toru Nishikawa, Daisuke Harada, Mari Yotsu-Yamashita, Kazuo Nagasawa

    Research output: Contribution to journalArticlepeer-review

    14 Citations (Scopus)

    Abstract

    11-Saxitoxinethanoic acid (SEA) is a member of the saxitoxin (STX) family of paralytic shellfish poisons, and contains an unusual C−C bond at the C11 position. Reported herein is a total synthesis of SEA. The key to our synthesis lies in a Mukaiyama aldol condensation reaction of silyl enol ether with glyoxylate in the presence of an anhydrous fluoride reagent, [Bu4N][Ph3SnF2], which directly constructs the crucial C−C bond at the C11 position in SEA. The NaVCh-inhibitory activities of SEA and its derivatives were evaluated by means of cell-based assay. SEA showed an IC50value of (47±12) nm, which is approximately twice as potent as decarbamoyl-STX (dcSTX).

    Original languageEnglish
    Pages (from-to)11600-11603
    Number of pages4
    JournalAngewandte Chemie - International Edition
    Volume55
    Issue number38
    DOIs
    Publication statusPublished - 2016 Sep 12

    Keywords

    • aldol reaction
    • heterocylces
    • natural products
    • saxitoxin
    • total synthesis

    ASJC Scopus subject areas

    • Catalysis
    • Chemistry(all)

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