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

Ahmad K. Haidar; Niels D. Kjeldsen; Nikolaj S. Troelsen; Viola Previtali; Kasper P. Lundquist; Thomas O. Larsen; Mads H. Clausen

doi:10.3390/molecules27020521

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

Ahmad K. Haidar, Niels D. Kjeldsen, Nikolaj S. Troelsen, Viola Previtali, Kasper P. Lundquist, Thomas O. Larsen, Mads H. Clausen^*

^*Corresponding author for this work

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Abstract

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.

Original language	English
Article number	521
Journal	Molecules
Volume	27
Issue number	2
Number of pages	9
ISSN	1420-3049
DOIs	https://doi.org/10.3390/molecules27020521
Publication status	Published - 2022

Keywords

Isoquinolines
Alkaloids
Epilepsy

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title = "A Concise Total Synthesis of the Fungal Isoquinoline Alkaloid TMC-120B",

abstract = "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. ",

keywords = "Isoquinolines, Alkaloids, Epilepsy",

author = "Haidar, {Ahmad K.} and Kjeldsen, {Niels D.} and Troelsen, {Nikolaj S.} and Viola Previtali and Lundquist, {Kasper P.} and Larsen, {Thomas O.} and Clausen, {Mads H.}",

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doi = "10.3390/molecules27020521",

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T1 - A Concise Total Synthesis of the Fungal Isoquinoline Alkaloid TMC-120B

AU - Haidar, Ahmad K.

AU - Kjeldsen, Niels D.

AU - Troelsen, Nikolaj S.

AU - Previtali, Viola

AU - Lundquist, Kasper P.

AU - Larsen, Thomas O.

AU - Clausen, Mads H.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - Isoquinolines

KW - Alkaloids

KW - Epilepsy

U2 - 10.3390/molecules27020521

DO - 10.3390/molecules27020521

M3 - Journal article

C2 - 35056832

SN - 1420-3049

VL - 27

JO - Molecules

JF - Molecules

IS - 2

M1 - 521

ER -

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

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