AI Article Synopsis
- Tetrodotoxin and its related compounds are potent sodium channel blockers with strong anesthetic and analgesic properties.
- The research outlines a scalable method for synthesizing Tetrodotoxin and 9-epiTetrodotoxin using furfuryl alcohol as a starting material, employing a series of carefully designed chemical reactions.
- Key techniques include stereoselective Diels-Alder reactions, functional group interconversions, and ruthenium-catalyzed reactions, resulting in a rapid production of the desired complex compounds.
Article Abstract
Tetrodotoxin and congeners are specific voltage-gated sodium channel blockers that exhibit remarkable anesthetic and analgesic effects. Here, we present a scalable asymmetric syntheses of Tetrodotoxin and 9-epiTetrodotoxin from the abundant chemical feedstock furfuryl alcohol. The optically pure cyclohexane skeleton is assembled via a stereoselective Diels-Alder reaction. The dense heteroatom substituents are established sequentially by a series of functional group interconversions on highly oxygenated cyclohexane frameworks, including a chemoselective cyclic anhydride opening, and a decarboxylative hydroxylation. An innovative SmI-mediated concurrent fragmentation, an oxo-bridge ring opening and ester reduction followed by an Upjohn dihydroxylation deliver the highly oxidized skeleton. Ruthenium-catalyzed oxidative alkyne cleavage and formation of the hemiaminal and orthoester under acidic conditions enable the rapid assembly of Tetrodotoxin, anhydro-Tetrodotoxin, 9-epiTetrodotoxin, and 9-epi lactone-Tetrodotoxin.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10806222 | PMC |
| http://dx.doi.org/10.1038/s41467-024-45037-0 | DOI Listing |
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