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

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• 作者：Chao Wang ; Mana Oki ; Toru Nishikawa ; Daisuke Harada ; Prof. Dr. Mari Yotsu-Yamashita and Prof. Dr. Kazuo Nagasawa
• 刊名：Angewandte Chemie International Edition
• 出版年：2016
• 出版时间：September 12, 2016
• 年：2016
• 卷：55
• 期：38
• 页码：11600-11603
• 全文大小：722K
• ISSN：1521-3773

文摘

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 Na_VCh-inhibitory activities of SEA and its derivatives were evaluated by means of cell-based assay. SEA showed an IC₅₀ value of (47±12) nm, which is approximately twice as potent as decarbamoyl-STX (dcSTX).