Diels–Alder Adducts of Morphinan-6,8-Dienes and Their Transformations
6,14-ethenomorphinans are semisynthetic opiate derivatives containing an ethylene bridge between positions 6 and 14 in ring-C of the morphine skeleton that imparts a rigid molecular structure. These compounds represent an important family of opioid receptor ligands in which the 6,14-etheno bridged s...
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| Format: | Article |
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MDPI AG
2022-04-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/9/2863 |
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| author | János Marton Anikó Fekete Paul Cumming Sándor Hosztafi Pál Mikecz Gjermund Henriksen |
| author_facet | János Marton Anikó Fekete Paul Cumming Sándor Hosztafi Pál Mikecz Gjermund Henriksen |
| author_sort | János Marton |
| collection | DOAJ |
| description | 6,14-ethenomorphinans are semisynthetic opiate derivatives containing an ethylene bridge between positions 6 and 14 in ring-C of the morphine skeleton that imparts a rigid molecular structure. These compounds represent an important family of opioid receptor ligands in which the 6,14-etheno bridged structural motif originates from a [4 + 2] cycloaddition of morphinan-6,8-dienes with dienophiles. Certain 6,14-ethenomorphinans having extremely high affinity for opioid receptors are often non-selective for opioid receptor subtypes, but this view is now undergoing some revision. The agonist 20<i>R</i>-etorphine and 20<i>R</i>-dihydroetorphine are several thousand times more potent analgesics than morphine, whereas diprenorphine is a high-affinity non-selective antagonist. The partial agonist buprenorphine is used as an analgesic in the management of post-operative pain or in substitution therapy for opiate addiction, sometimes in combination with the non-selective antagonist naloxone. In the context of the current opioid crisis, we communicated a summary of several decades of work toward generating opioid analgesics with lesser side effects or abuse potential. Our summary placed a focus on Diels–Alder reactions of morphinan-6,8-dienes and subsequent transformations of the cycloadducts. We also summarized the pharmacological aspects of radiolabeled 6,14-ethenomorphinans used in molecular imaging of opioid receptors. |
| first_indexed | 2024-03-10T03:53:56Z |
| format | Article |
| id | doaj.art-af20237bf0bf4df0875ae85eccac937f |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T03:53:56Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-af20237bf0bf4df0875ae85eccac937f2023-11-23T08:50:46ZengMDPI AGMolecules1420-30492022-04-01279286310.3390/molecules27092863Diels–Alder Adducts of Morphinan-6,8-Dienes and Their TransformationsJános Marton0Anikó Fekete1Paul Cumming2Sándor Hosztafi3Pál Mikecz4Gjermund Henriksen5ABX Advanced Biochemical Compounds Biomedizinische Forschungsreagenzien GmbH, Heinrich-Glaeser-Strasse 10-14, D-01454 Radeberg, GermanyDepartment of Medical Imaging, Division of Nuclear Medicine and Translational Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, HungaryDepartment of Nuclear Medicine, Bern University Hospital, Freiburgstraße 18, 3010 Bern, SwitzerlandInstitute of Pharmaceutical Chemistry, Semmelweis Medical University, Högyes Endre utca 9, H-1092 Budapest, HungaryDepartment of Medical Imaging, Division of Nuclear Medicine and Translational Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, HungaryNorwegian Medical Cyclotron Centre Ltd., Sognsvannsveien 20, N-0372 Oslo, Norway6,14-ethenomorphinans are semisynthetic opiate derivatives containing an ethylene bridge between positions 6 and 14 in ring-C of the morphine skeleton that imparts a rigid molecular structure. These compounds represent an important family of opioid receptor ligands in which the 6,14-etheno bridged structural motif originates from a [4 + 2] cycloaddition of morphinan-6,8-dienes with dienophiles. Certain 6,14-ethenomorphinans having extremely high affinity for opioid receptors are often non-selective for opioid receptor subtypes, but this view is now undergoing some revision. The agonist 20<i>R</i>-etorphine and 20<i>R</i>-dihydroetorphine are several thousand times more potent analgesics than morphine, whereas diprenorphine is a high-affinity non-selective antagonist. The partial agonist buprenorphine is used as an analgesic in the management of post-operative pain or in substitution therapy for opiate addiction, sometimes in combination with the non-selective antagonist naloxone. In the context of the current opioid crisis, we communicated a summary of several decades of work toward generating opioid analgesics with lesser side effects or abuse potential. Our summary placed a focus on Diels–Alder reactions of morphinan-6,8-dienes and subsequent transformations of the cycloadducts. We also summarized the pharmacological aspects of radiolabeled 6,14-ethenomorphinans used in molecular imaging of opioid receptors.https://www.mdpi.com/1420-3049/27/9/2863morphine alkaloidsopioid receptorsmorphinan-6,8-dienesDiels–Alder reactionGrignard addition<i>O</i>-demethylation |
| spellingShingle | János Marton Anikó Fekete Paul Cumming Sándor Hosztafi Pál Mikecz Gjermund Henriksen Diels–Alder Adducts of Morphinan-6,8-Dienes and Their Transformations Molecules morphine alkaloids opioid receptors morphinan-6,8-dienes Diels–Alder reaction Grignard addition <i>O</i>-demethylation |
| title | Diels–Alder Adducts of Morphinan-6,8-Dienes and Their Transformations |
| title_full | Diels–Alder Adducts of Morphinan-6,8-Dienes and Their Transformations |
| title_fullStr | Diels–Alder Adducts of Morphinan-6,8-Dienes and Their Transformations |
| title_full_unstemmed | Diels–Alder Adducts of Morphinan-6,8-Dienes and Their Transformations |
| title_short | Diels–Alder Adducts of Morphinan-6,8-Dienes and Their Transformations |
| title_sort | diels alder adducts of morphinan 6 8 dienes and their transformations |
| topic | morphine alkaloids opioid receptors morphinan-6,8-dienes Diels–Alder reaction Grignard addition <i>O</i>-demethylation |
| url | https://www.mdpi.com/1420-3049/27/9/2863 |
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