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7429229 
Journal Article 
Total synthesis of saxitoxins 
Nagasawa, K 
2021 
1 
Yuki Gosei Kagaku Kyokaishi
ISSN: 0037-9980 
Society of Synthetic Organic Chemistry 
79 
1 
43-53 
Japanese 
WOS:000640284800006 
This review deals with our synthetic efforts for guanidine alkaloid of saxitoxin (STX), a paralytic shellfish toxin. STX shows potent inhibitory activity against voltage-gated sodium channels (Na Vs), which are membrane proteins that involve in the generation and propagation of action potentials in neurons. More than 50 analogs of STX have been isolated from nature, and these analogs commonly possess characteristic tricyclic core skeleton including two kinds of 5-memberd and 6-memberd cyclic guanidine. For the synthesis of the core structure, we have developed a neighboring acyl group assisted cyclization strategy to give tricycle with a fully protected form of saxitoxinol under quite mild conditions. This key intermediate allows us total synthesis of (+)-decarbamoyl saxitoxin (dcSTX), (+)-gonyautoxin 3 (GTX3) including and STX. Besides, we have achieved the synthesis of 11-saxitoxinethanoic acid (SEA), which is an unusual STX derivative bearing carbon-carbon bond at the C11 position by applying Mukaiyama aldol condensation reaction with silyl enolether derived from the key intermediate of fully protected saxitoxinol. Na V inhibitory activities of some synthetic derivatives with C11-substituents in STX were also described. © 2021 Society of Synthetic Organic Chemistry. All rights reserved. 
11-saxitoxinethanoic acid; Gaunyotoxin; Guanidine alkaloids; Saxitoxin; Structure-activity-relationship studies; Total synthesis; Voltage-gated sodium channel inhibitor; Zetekitoxin AB; Binary alloys; Carbon; Condensation reactions; Electrophysiology; Ketones; Proteins; Reaction intermediates; Sodium alloys; Synthesis (chemical); Vanadium alloys; Action potentials; Carbon-carbon bond; Fully protected; Guanidine alkaloids; Inhibitory activity; Membrane proteins; Mukaiyama aldols; Paralytic shellfish toxins; Cyclization 
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