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...
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| Veröffentlicht in: | Chemical & pharmaceutical bulletin 1994/07/15, Vol.42(7), pp.1432-1436 |
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| container_title | Chemical & pharmaceutical bulletin |
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| creator | OKABE, Kazuaki NATSUME, Mitsutaka |
| description | 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. |
| doi_str_mv | 10.1248/cpb.42.1432 |
| format | Article |
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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. 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Pharm. Bull.</addtitle><description>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.</description><subject>Analgesics - chemical synthesis</subject><subject>Animals</subject><subject>Anura</subject><subject>Bridged Bicyclo Compounds - chemical synthesis</subject><subject>Bridged Bicyclo Compounds, Heterocyclic</subject><subject>Chemistry</subject><subject>epibatidine</subject><subject>Epipedobates tricolor</subject><subject>Exact sciences and technology</subject><subject>Freshwater</subject><subject>Heterocyclic compounds</subject><subject>Heterocyclic compounds with only one n hetero atom and condensed derivatives</subject><subject>non-opioid analgesic</subject><subject>Organic chemistry</subject><subject>poison frog constituent</subject><subject>Preparations and properties</subject><subject>Pyridines - chemical synthesis</subject><subject>Stereoisomerism</subject><subject>total synthesis</subject><issn>0009-2363</issn><issn>1347-5223</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkE9LHDEchkNp0a321LMwUJGWOmv-TpKjWG0L4h-055DJJGuW2WRMZg9-rH4FP5kZdtlCL_kd3of3DQ8AnxGcI0zFmRnaOcVzRAl-B2aIUF4zjMl7MIMQyhqThuyDjzkvIcQMcrIH9rjEhDbNDNw_xlH31cNLGJ9s9rmKrtLVVYqL6i76HMNp9fX177f6cvCtHn3ngz0twF0cbRirmxjqOPjou-o86H5RGswh-OB0n-2n7T0Af64uHy9-1de3P39fnF_XhgmEa2M7LLAzDBFjiXbMdUwK6BhExhopBJRGc80llwabtsOSG8tF67RFkDeMHICTTe-Q4vPa5lGtfDa273WwcZ0VahouJaQF_PIfuIzrVL5bGNpALDjFolDfN5RJMedknRqSX-n0ohBUk2ZVNCuK1aS50EfbznW7st2O3Xot-fE219no3iUdjM87jFAIqZhqfmywZR71wu5ynUZvejtNIsnENMs3z7T-L37SSdlA3gBVHJt8</recordid><startdate>1994</startdate><enddate>1994</enddate><creator>OKABE, Kazuaki</creator><creator>NATSUME, Mitsutaka</creator><general>The Pharmaceutical Society of Japan</general><general>Maruzen</general><general>Japan Science and Technology Agency</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>H94</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>F1W</scope><scope>FR3</scope><scope>H95</scope><scope>H99</scope><scope>L.F</scope><scope>L.G</scope><scope>P64</scope></search><sort><creationdate>1994</creationdate><title>Total Synthesis of a Frog Poison, (±)-Epibatidine, a Potent Non-opioid Analgesic</title><author>OKABE, Kazuaki ; NATSUME, Mitsutaka</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5812-ced282fc513ce3af5fd5980f501cec98809ca7a7979c2cbd297ce78bfae107653</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Analgesics - chemical synthesis</topic><topic>Animals</topic><topic>Anura</topic><topic>Bridged Bicyclo Compounds - chemical synthesis</topic><topic>Bridged Bicyclo Compounds, Heterocyclic</topic><topic>Chemistry</topic><topic>epibatidine</topic><topic>Epipedobates tricolor</topic><topic>Exact sciences and technology</topic><topic>Freshwater</topic><topic>Heterocyclic compounds</topic><topic>Heterocyclic compounds with only one n hetero atom and condensed derivatives</topic><topic>non-opioid analgesic</topic><topic>Organic chemistry</topic><topic>poison frog constituent</topic><topic>Preparations and properties</topic><topic>Pyridines - chemical synthesis</topic><topic>Stereoisomerism</topic><topic>total synthesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>OKABE, Kazuaki</creatorcontrib><creatorcontrib>NATSUME, Mitsutaka</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Engineering Research Database</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>ASFA: Marine Biotechnology Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Marine Biotechnology Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Chemical & pharmaceutical bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>OKABE, Kazuaki</au><au>NATSUME, Mitsutaka</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Total Synthesis of a Frog Poison, (±)-Epibatidine, a Potent Non-opioid Analgesic</atitle><jtitle>Chemical & pharmaceutical bulletin</jtitle><addtitle>Chem. Pharm. Bull.</addtitle><date>1994</date><risdate>1994</risdate><volume>42</volume><issue>7</issue><spage>1432</spage><epage>1436</epage><pages>1432-1436</pages><issn>0009-2363</issn><eissn>1347-5223</eissn><coden>CPBTAL</coden><abstract>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.</abstract><cop>Tokyo</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>7923466</pmid><doi>10.1248/cpb.42.1432</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0009-2363 |
| ispartof | Chemical and Pharmaceutical Bulletin, 1994/07/15, Vol.42(7), pp.1432-1436 |
| issn | 0009-2363 1347-5223 |
| language | eng |
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| source | J-STAGE Free; MEDLINE; EZB-FREE-00999 freely available EZB journals; Free Full-Text Journals in Chemistry |
| subjects | Analgesics - chemical synthesis Animals Anura Bridged Bicyclo Compounds - chemical synthesis Bridged Bicyclo Compounds, Heterocyclic Chemistry epibatidine Epipedobates tricolor Exact sciences and technology Freshwater Heterocyclic compounds Heterocyclic compounds with only one n hetero atom and condensed derivatives non-opioid analgesic Organic chemistry poison frog constituent Preparations and properties Pyridines - chemical synthesis Stereoisomerism total synthesis |
| title | Total Synthesis of a Frog Poison, (±)-Epibatidine, a Potent Non-opioid Analgesic |
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