1-Oxo-5-hydroxytryptamine: a surprisingly potent agonist of the 5-HT3 (serotonin) receptor.
A novel synthetic route to 1-oxo-5-hydroxytryptamine, the benzofuran analogue of serotonin, has been developed. The new synthesis proceeds via the [3+2] cycloaddition of p-benzoquinone and 2,3-dihydrofuran, followed by a Lewis acid-catalyzed isomerization. This molecule proves to be a competent agonist (equipotent to serotonin) of the 5-HT3 receptor, demonstrating that the indolic proton of serotonin is not essential to its activation of the receptor.
Kedrowski
Sean M A
SM
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
Bower
Kiowa S
KS
Dougherty
Dennis A
DA
D001572:Benzofurans / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis*
C523377:1-oxo-5-hydroxytryptamine; D001572:Benzofurans; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D012701:Serotonin; C105430:benzofuran