Total Synthesis of 11‐Saxitoxinethanoic Acid and Evaluation of its Inhibitory Activity on Voltage‐Gated Sodium Channels |
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| Authors: | Chao Wang Mana Oki Toru Nishikawa Daisuke Harada Prof Dr Mari Yotsu‐Yamashita Prof Dr Kazuo Nagasawa |
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| Affiliation: | 1. Department of Biotechnology and Life Science, Faculty of Technology, Tokyo University of Agriculture and Technology, Tokyo, Japan;2. Graduate School of Agricultural Science, Tohoku University, Aoba-ku, Sendai, Japan |
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| 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 IC50 value of (47±12) nm , which is approximately twice as potent as decarbamoyl‐STX (dcSTX). |
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| Keywords: | aldol reaction heterocylces natural products saxitoxin total synthesis |
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