A Concise Total Synthesis of the Fungal Isoquinoline Alkaloid TMC-120B

Recent reports of antiepileptic activity of the fungal alkaloid TMC-120B have renewed the interest in this natural product. Previous total syntheses of TMC-120B comprise many steps and have low overall yields (11–17 steps, 1.5–2.9% yield). Thus, to access this compound more efficiently, we herein pr...

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Detalles Bibliográficos
Autores principales: Haidar, Ahmad K., Kjeldsen, Niels D., Troelsen, Nikolaj S., Previtali, Viola, Lundquist, Kasper P., Larsen, Thomas O., Clausen, Mads H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779217/
https://www.ncbi.nlm.nih.gov/pubmed/35056832
http://dx.doi.org/10.3390/molecules27020521
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author Haidar, Ahmad K.
Kjeldsen, Niels D.
Troelsen, Nikolaj S.
Previtali, Viola
Lundquist, Kasper P.
Larsen, Thomas O.
Clausen, Mads H.
author_facet Haidar, Ahmad K.
Kjeldsen, Niels D.
Troelsen, Nikolaj S.
Previtali, Viola
Lundquist, Kasper P.
Larsen, Thomas O.
Clausen, Mads H.
author_sort Haidar, Ahmad K.
collection PubMed
description Recent reports of antiepileptic activity of the fungal alkaloid TMC-120B have renewed the interest in this natural product. Previous total syntheses of TMC-120B comprise many steps and have low overall yields (11–17 steps, 1.5–2.9% yield). Thus, to access this compound more efficiently, we herein present a concise and significantly improved total synthesis of the natural product. Our short synthesis relies on two key cyclization steps to assemble the central scaffold: isoquinoline formation via an ethynyl-imino cyclization and an intramolecular Friedel-Crafts reaction to form the furanone.
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spelling pubmed-87792172022-01-22 A Concise Total Synthesis of the Fungal Isoquinoline Alkaloid TMC-120B Haidar, Ahmad K. Kjeldsen, Niels D. Troelsen, Nikolaj S. Previtali, Viola Lundquist, Kasper P. Larsen, Thomas O. Clausen, Mads H. Molecules Article Recent reports of antiepileptic activity of the fungal alkaloid TMC-120B have renewed the interest in this natural product. Previous total syntheses of TMC-120B comprise many steps and have low overall yields (11–17 steps, 1.5–2.9% yield). Thus, to access this compound more efficiently, we herein present a concise and significantly improved total synthesis of the natural product. Our short synthesis relies on two key cyclization steps to assemble the central scaffold: isoquinoline formation via an ethynyl-imino cyclization and an intramolecular Friedel-Crafts reaction to form the furanone. MDPI 2022-01-14 /pmc/articles/PMC8779217/ /pubmed/35056832 http://dx.doi.org/10.3390/molecules27020521 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Haidar, Ahmad K.
Kjeldsen, Niels D.
Troelsen, Nikolaj S.
Previtali, Viola
Lundquist, Kasper P.
Larsen, Thomas O.
Clausen, Mads H.
A Concise Total Synthesis of the Fungal Isoquinoline Alkaloid TMC-120B
title A Concise Total Synthesis of the Fungal Isoquinoline Alkaloid TMC-120B
title_full A Concise Total Synthesis of the Fungal Isoquinoline Alkaloid TMC-120B
title_fullStr A Concise Total Synthesis of the Fungal Isoquinoline Alkaloid TMC-120B
title_full_unstemmed A Concise Total Synthesis of the Fungal Isoquinoline Alkaloid TMC-120B
title_short A Concise Total Synthesis of the Fungal Isoquinoline Alkaloid TMC-120B
title_sort concise total synthesis of the fungal isoquinoline alkaloid tmc-120b
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779217/
https://www.ncbi.nlm.nih.gov/pubmed/35056832
http://dx.doi.org/10.3390/molecules27020521
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