Synthesis of MDM2-p53 Inhibitor BI-0282 via a Dipolar Cycloaddition and Late-Stage Davis–Beirut Reaction

[Image: see text] Herein, we report the structure and synthesis of the potent MDM2-p53 inhibitor BI-0282. The complex spirooxindole scaffold bearing four stereocenters embedded in a rigid polycyclic ring-system was effectively prepared on a multi-gram scale in only five synthesis steps employing a t...

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Autores principales: Ramharter, Juergen, Kulhanek, Michael, Dettling, Maike, Gmaschitz, Gerhard, Karolyi-Oezguer, Jale, Weinstabl, Harald, Gollner, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9396656/
https://www.ncbi.nlm.nih.gov/pubmed/36032359
http://dx.doi.org/10.1021/acs.oprd.2c00192
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author Ramharter, Juergen
Kulhanek, Michael
Dettling, Maike
Gmaschitz, Gerhard
Karolyi-Oezguer, Jale
Weinstabl, Harald
Gollner, Andreas
author_facet Ramharter, Juergen
Kulhanek, Michael
Dettling, Maike
Gmaschitz, Gerhard
Karolyi-Oezguer, Jale
Weinstabl, Harald
Gollner, Andreas
author_sort Ramharter, Juergen
collection PubMed
description [Image: see text] Herein, we report the structure and synthesis of the potent MDM2-p53 inhibitor BI-0282. The complex spirooxindole scaffold bearing four stereocenters embedded in a rigid polycyclic ring-system was effectively prepared on a multi-gram scale in only five synthesis steps employing a three-component 1,3-dipolar cycloaddition and a late-stage Davis–Beirut reaction as key steps.
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spelling pubmed-93966562022-08-24 Synthesis of MDM2-p53 Inhibitor BI-0282 via a Dipolar Cycloaddition and Late-Stage Davis–Beirut Reaction Ramharter, Juergen Kulhanek, Michael Dettling, Maike Gmaschitz, Gerhard Karolyi-Oezguer, Jale Weinstabl, Harald Gollner, Andreas Org Process Res Dev [Image: see text] Herein, we report the structure and synthesis of the potent MDM2-p53 inhibitor BI-0282. The complex spirooxindole scaffold bearing four stereocenters embedded in a rigid polycyclic ring-system was effectively prepared on a multi-gram scale in only five synthesis steps employing a three-component 1,3-dipolar cycloaddition and a late-stage Davis–Beirut reaction as key steps. American Chemical Society 2022-07-07 2022-08-19 /pmc/articles/PMC9396656/ /pubmed/36032359 http://dx.doi.org/10.1021/acs.oprd.2c00192 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Ramharter, Juergen
Kulhanek, Michael
Dettling, Maike
Gmaschitz, Gerhard
Karolyi-Oezguer, Jale
Weinstabl, Harald
Gollner, Andreas
Synthesis of MDM2-p53 Inhibitor BI-0282 via a Dipolar Cycloaddition and Late-Stage Davis–Beirut Reaction
title Synthesis of MDM2-p53 Inhibitor BI-0282 via a Dipolar Cycloaddition and Late-Stage Davis–Beirut Reaction
title_full Synthesis of MDM2-p53 Inhibitor BI-0282 via a Dipolar Cycloaddition and Late-Stage Davis–Beirut Reaction
title_fullStr Synthesis of MDM2-p53 Inhibitor BI-0282 via a Dipolar Cycloaddition and Late-Stage Davis–Beirut Reaction
title_full_unstemmed Synthesis of MDM2-p53 Inhibitor BI-0282 via a Dipolar Cycloaddition and Late-Stage Davis–Beirut Reaction
title_short Synthesis of MDM2-p53 Inhibitor BI-0282 via a Dipolar Cycloaddition and Late-Stage Davis–Beirut Reaction
title_sort synthesis of mdm2-p53 inhibitor bi-0282 via a dipolar cycloaddition and late-stage davis–beirut reaction
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9396656/
https://www.ncbi.nlm.nih.gov/pubmed/36032359
http://dx.doi.org/10.1021/acs.oprd.2c00192
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