title: Total Synthesis of 11-Saxitoxinethanoic Acid and Evaluation of its Inhibitory Activity on Voltage-Gated Sodium Channels.
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, [Bu4 N][Ph3 SnF2 ], which directly constructs the crucial C-C bond at the C11 position in SEA. The NaV Ch-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).
authors: Department of Biotechnology and Life Science, Faculty of Technology, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo, 184-8588, Japan.
authors: Chao
authors: C
authors: Wang
authors: Department of Biotechnology and Life Science, Faculty of Technology, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo, 184-8588, Japan.
authors: Mana
authors: M
authors: Oki
authors: Department of Biotechnology and Life Science, Faculty of Technology, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo, 184-8588, Japan.
authors: Toru
authors: T
authors: Nishikawa
authors: Department of Biotechnology and Life Science, Faculty of Technology, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo, 184-8588, Japan.
authors: Daisuke
authors: D
authors: Harada
authors: Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiya, Aoba-ku, Sendai, 981-8555, Japan.
authors: Mari
authors: M
authors: Yotsu-Yamashita
authors: Department of Biotechnology and Life Science, Faculty of Technology, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo, 184-8588, Japan. knaga@cc.tuat.ac.jp.
authors: Kazuo
authors: K
authors: Nagasawa
keywords: aldol reaction; heterocylces; natural products; saxitoxin; total synthesis