Studies Concerned with the Structure and Synthesis of the Anti‐viral Tropolone Glycoside Liriosmaside A

Abstract A bromotropone corresponding to the agylcone of the glycosylated sesquiterpenoid natural product liriosmaside A has been prepared over ten steps and in a fully regio‐controlled manner through the gem‐dibromocyclopropane‐mediated ring‐expansion of a readily accessible decalenone. A Pd[0]‐med...

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Main Authors: Qi Chen, Yaping Zhan, Michael G. Gardiner, Zeinab G. Khalil, Amila A. Dewa, Thulasi Sritharan, Robert J. Capon, Ping Lan, Shen Tan, Martin G. Banwell
Format: Article
Language:English
Published: Wiley-VCH 2025-08-01
Series:ChemistryOpen
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Online Access:https://doi.org/10.1002/open.202500011
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author Qi Chen
Yaping Zhan
Michael G. Gardiner
Zeinab G. Khalil
Amila A. Dewa
Thulasi Sritharan
Robert J. Capon
Ping Lan
Shen Tan
Martin G. Banwell
author_facet Qi Chen
Yaping Zhan
Michael G. Gardiner
Zeinab G. Khalil
Amila A. Dewa
Thulasi Sritharan
Robert J. Capon
Ping Lan
Shen Tan
Martin G. Banwell
author_sort Qi Chen
collection DOAJ
description Abstract A bromotropone corresponding to the agylcone of the glycosylated sesquiterpenoid natural product liriosmaside A has been prepared over ten steps and in a fully regio‐controlled manner through the gem‐dibromocyclopropane‐mediated ring‐expansion of a readily accessible decalenone. A Pd[0]‐mediated glucosylation reaction applied to this bromotropone afforded a product mixture from which an enantiomerically pure cross‐coupling product could be obtained and its structure confirmed through single‐crystal X‐ray analysis of a derivative. Various (unsuccessful) attempts are described to selectively acylate the last compound and thereby install the 3‐hydroxy‐3‐methylglutaric acid or HMGA‐containing side chain of the title natural product. A literature survey of other natural products embodying the HMGA motif suggest that liriosmaside A and its co‐metabolite liriosmaside B could be S‐configured at C3”. The evaluation of the glucosylated tropone in a series of anti‐bacterial, anti‐fungal and cytotoxicity assays reveals that it is inactive in all of these and so emphasizing the prospect that this and related troponoids, including the natural products liriosmaside A and B, can serve as useful models for new anti‐viral agents.
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spelling doaj-art-0388037916ad40ebbbd14b152b4575ed2025-08-21T12:05:32ZengWiley-VCHChemistryOpen2191-13632025-08-01148n/an/a10.1002/open.202500011Studies Concerned with the Structure and Synthesis of the Anti‐viral Tropolone Glycoside Liriosmaside AQi Chen0Yaping Zhan1Michael G. Gardiner2Zeinab G. Khalil3Amila A. Dewa4Thulasi Sritharan5Robert J. Capon6Ping Lan7Shen Tan8Martin G. Banwell9Institute for Advanced and Applied Chemical Synthesis College of Pharmacy Jinan University Guangzhou 510632 ChinaCollege of Pharmacy Jinan University Guangzhou 510632 ChinaResearch School of Chemistry Institute of Advanced Studies The Australian National University Canberra ACT 2601 AustraliaInstitute for Molecular Bioscience University of Queensland St Lucia QLD 4072 AustraliaInstitute for Molecular Bioscience University of Queensland St Lucia QLD 4072 AustraliaInstitute for Molecular Bioscience University of Queensland St Lucia QLD 4072 AustraliaInstitute for Molecular Bioscience University of Queensland St Lucia QLD 4072 AustraliaInstitute for Advanced and Applied Chemical Synthesis College of Pharmacy Jinan University Guangzhou 510632 ChinaInstitute for Advanced and Applied Chemical Synthesis College of Pharmacy Jinan University Guangzhou 510632 ChinaInstitute for Advanced and Applied Chemical Synthesis College of Pharmacy Jinan University Guangzhou 510632 ChinaAbstract A bromotropone corresponding to the agylcone of the glycosylated sesquiterpenoid natural product liriosmaside A has been prepared over ten steps and in a fully regio‐controlled manner through the gem‐dibromocyclopropane‐mediated ring‐expansion of a readily accessible decalenone. A Pd[0]‐mediated glucosylation reaction applied to this bromotropone afforded a product mixture from which an enantiomerically pure cross‐coupling product could be obtained and its structure confirmed through single‐crystal X‐ray analysis of a derivative. Various (unsuccessful) attempts are described to selectively acylate the last compound and thereby install the 3‐hydroxy‐3‐methylglutaric acid or HMGA‐containing side chain of the title natural product. A literature survey of other natural products embodying the HMGA motif suggest that liriosmaside A and its co‐metabolite liriosmaside B could be S‐configured at C3”. The evaluation of the glucosylated tropone in a series of anti‐bacterial, anti‐fungal and cytotoxicity assays reveals that it is inactive in all of these and so emphasizing the prospect that this and related troponoids, including the natural products liriosmaside A and B, can serve as useful models for new anti‐viral agents.https://doi.org/10.1002/open.202500011troponering-expansioncross-couplingglycosylationanti-viral
spellingShingle Qi Chen
Yaping Zhan
Michael G. Gardiner
Zeinab G. Khalil
Amila A. Dewa
Thulasi Sritharan
Robert J. Capon
Ping Lan
Shen Tan
Martin G. Banwell
Studies Concerned with the Structure and Synthesis of the Anti‐viral Tropolone Glycoside Liriosmaside A
ChemistryOpen
tropone
ring-expansion
cross-coupling
glycosylation
anti-viral
title Studies Concerned with the Structure and Synthesis of the Anti‐viral Tropolone Glycoside Liriosmaside A
title_full Studies Concerned with the Structure and Synthesis of the Anti‐viral Tropolone Glycoside Liriosmaside A
title_fullStr Studies Concerned with the Structure and Synthesis of the Anti‐viral Tropolone Glycoside Liriosmaside A
title_full_unstemmed Studies Concerned with the Structure and Synthesis of the Anti‐viral Tropolone Glycoside Liriosmaside A
title_short Studies Concerned with the Structure and Synthesis of the Anti‐viral Tropolone Glycoside Liriosmaside A
title_sort studies concerned with the structure and synthesis of the anti viral tropolone glycoside liriosmaside a
topic tropone
ring-expansion
cross-coupling
glycosylation
anti-viral
url https://doi.org/10.1002/open.202500011
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