Divergent Synthesis of Natural Derivatives of (+)-Saxitoxin Including 11-Saxitoxinethanoic Acid.

ABSTRACT: The bis-guanidinium toxins are a collection of natural products that display nanomolar potency against select isoforms of eukaryotic voltage-gated Na⁺ ion channels. We describe a synthetic strategy that enables access to four of these poisons, namely 11-saxitoxinethanoic acid, C13-acetoxy saxitoxin, decarbamoyl saxitoxin, and saxitoxin. Highlights of this work include an unusual Mislow-Evans rearrangement and a late-stage Stille ketene acetal coupling. The IC₅₀ value of 11-saxitoxinethanoic acid was measured against rat Na_V 1.4, and found to be 17.0 nm, similar to those of the sulfated toxins gonyautoxin II and III.

SUBMITTER: Walker JR 

PROVIDER: S-EPMC6426452 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature