Total synthesis of a frog poison, (+/-)-epibatidine, a potent non-opioid analgesic.
A non-opioid analgesic, epibatidine (1), isolated from Ecuadoran poison frogs was synthesized in the racemic form starting from a readily available compound 2. A partial Curtius rearrangement product 5 of 2 was converted into 12c by way of the ketone 3 and its condensation product with the pyridine moiety 9c, and catalytic hydrogenation of 12c was specifically conducted in hydrochloric acid-containing 2-propanol for the preferential formation of an exo-product 15b. Conversion of the substituent from 15b to 15a in a single operation using the Vilsmeier reagent, followed by deprotection of the p-toluenesulfonyl group with hydrobromic acid completed an eight-step synthesis of (+/-)-1 from 2.
Okabe
K
K
Research Foundation Itsuu Laboratory, Tokyo, Japan.
Natsume
M
M
D000700:Analgesics / Q000138:chemical synthesis*; D000818:Animals; D001001:Anura; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D011725:Pyridines / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000700:Analgesics; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D011725:Pyridines; C082748:epibatidine