A cyanide-catalyzed imino-Stetter reaction enables the concise total syntheses of rucaparib
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Park, Jinjae | - |
dc.contributor.author | Cheon, Cheol-Hong | - |
dc.date.accessioned | 2022-08-25T13:41:05Z | - |
dc.date.available | 2022-08-25T13:41:05Z | - |
dc.date.created | 2022-08-25 | - |
dc.date.issued | 2022-07-21 | - |
dc.identifier.issn | 2046-2069 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/143354 | - |
dc.description.abstract | Two routes toward the synthesis of rucaparib, an FDA-approved drug used for the treatment of ovarian and prostate cancers, have been developed from commercially available starting materials utilizing the cyanide-catalyzed imino-Stetter reaction as the key step for the construction of the indole motif bearing all the desired substituents in their correct positions. In the first-generation synthesis, meta-fluorobenzoate, the starting material currently used in the process chemistry route of rucaparib, was converted into 4,6-disubstituted 2-aminocinnamic acid derivatives (ester or amide). The cyanide-catalyzed imino-Stetter reaction of aldimines derived from the resulting 2-aminocinnamic acid derivatives and a commercially available aldehyde afforded the desired indole-3-acetic acid derivatives. The final azepinone formation completed the total synthesis of rucaparib in 27% overall yield. To resolve the issues raised in the first-generation synthesis, we further developed a second-generation synthesis of rucaparib. The Heck reaction of a commercially available ortho-iodoaniline derivative with acrylonitrile provided 4,6-disubstituted 2-aminocinnamonitrile, which was subjected to the imino-Stetter reaction with the same aldehyde to provide the desired indole-3-acetonitrile product. Subsequent construction of the azepinone scaffold completed the total synthesis of rucaparib in 59% overall yield over three separation operations. The synthetic strategy reported herein can provide a highly practical route to access rucaparib from commercially available starting materials (5.2% overall yield in the current process chemistry route vs. 59% overall yield in the second-generation synthesis). | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | ROYAL SOC CHEMISTRY | - |
dc.subject | CHEMOSELECTIVE REDUCTION | - |
dc.subject | SELECTIVE SYNTHESIS | - |
dc.subject | NITRILES | - |
dc.subject | SECONDARY | - |
dc.subject | HYDROGENATION | - |
dc.subject | DERIVATIVES | - |
dc.subject | TERTIARY | - |
dc.subject | AMIDES | - |
dc.subject | AMINES | - |
dc.title | A cyanide-catalyzed imino-Stetter reaction enables the concise total syntheses of rucaparib | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Cheon, Cheol-Hong | - |
dc.identifier.doi | 10.1039/d2ra03619c | - |
dc.identifier.scopusid | 2-s2.0-85136605826 | - |
dc.identifier.wosid | 000834511100001 | - |
dc.identifier.bibliographicCitation | RSC ADVANCES, v.12, no.33, pp.21172 - 21180 | - |
dc.relation.isPartOf | RSC ADVANCES | - |
dc.citation.title | RSC ADVANCES | - |
dc.citation.volume | 12 | - |
dc.citation.number | 33 | - |
dc.citation.startPage | 21172 | - |
dc.citation.endPage | 21180 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Multidisciplinary | - |
dc.subject.keywordPlus | AMIDES | - |
dc.subject.keywordPlus | AMINES | - |
dc.subject.keywordPlus | CHEMOSELECTIVE REDUCTION | - |
dc.subject.keywordPlus | DERIVATIVES | - |
dc.subject.keywordPlus | HYDROGENATION | - |
dc.subject.keywordPlus | NITRILES | - |
dc.subject.keywordPlus | SECONDARY | - |
dc.subject.keywordPlus | SELECTIVE SYNTHESIS | - |
dc.subject.keywordPlus | TERTIARY | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
(02841) 서울특별시 성북구 안암로 14502-3290-1114
COPYRIGHT © 2021 Korea University. All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.