Total Synthesis of the Antimitotic Marine Macrolide (−)-Leiodermatolide**

Leiodermatolide is an antimitotic macrolide isolated from the marine sponge Leiodermatium sp. whose potentially novel tubulin-targeting mechanism of action makes it an exciting lead for anticancer drug discovery. In pursuit of a sustainable supply, we report a highly stereocontrolled total synthesis...

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Detalles Bibliográficos
Autores principales: Paterson, Ian, Ng, Kenneth K-H, Williams, Simon, Millican, David C, Dalby, Stephen M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: WILEY-VCH Verlag 2014
Materias:
Communications
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4499261/
https://www.ncbi.nlm.nih.gov/pubmed/24481746
http://dx.doi.org/10.1002/anie.201310164
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author Paterson, Ian
Ng, Kenneth K-H
Williams, Simon
Millican, David C
Dalby, Stephen M
author_facet Paterson, Ian
Ng, Kenneth K-H
Williams, Simon
Millican, David C
Dalby, Stephen M
author_sort Paterson, Ian
collection PubMed
description Leiodermatolide is an antimitotic macrolide isolated from the marine sponge Leiodermatium sp. whose potentially novel tubulin-targeting mechanism of action makes it an exciting lead for anticancer drug discovery. In pursuit of a sustainable supply, we report a highly stereocontrolled total synthesis (3.2 % yield) based on a convergent sequence of palladium-mediated fragment assembly and macrolactonization. Boron-mediated aldol reactions were used to configure the three key fragments 2, 5, and 6 by employing the appropriate enantiomer of the lactate-derived ketone 7.
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spelling pubmed-44992612015-07-16 Total Synthesis of the Antimitotic Marine Macrolide (−)-Leiodermatolide** Paterson, Ian Ng, Kenneth K-H Williams, Simon Millican, David C Dalby, Stephen M Angew Chem Int Ed Engl Communications Leiodermatolide is an antimitotic macrolide isolated from the marine sponge Leiodermatium sp. whose potentially novel tubulin-targeting mechanism of action makes it an exciting lead for anticancer drug discovery. In pursuit of a sustainable supply, we report a highly stereocontrolled total synthesis (3.2 % yield) based on a convergent sequence of palladium-mediated fragment assembly and macrolactonization. Boron-mediated aldol reactions were used to configure the three key fragments 2, 5, and 6 by employing the appropriate enantiomer of the lactate-derived ketone 7. WILEY-VCH Verlag 2014-03-03 2014-01-30 /pmc/articles/PMC4499261/ /pubmed/24481746 http://dx.doi.org/10.1002/anie.201310164 Text en © 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Communications
Paterson, Ian
Ng, Kenneth K-H
Williams, Simon
Millican, David C
Dalby, Stephen M
Total Synthesis of the Antimitotic Marine Macrolide (−)-Leiodermatolide**
title Total Synthesis of the Antimitotic Marine Macrolide (−)-Leiodermatolide**
title_full Total Synthesis of the Antimitotic Marine Macrolide (−)-Leiodermatolide**
title_fullStr Total Synthesis of the Antimitotic Marine Macrolide (−)-Leiodermatolide**
title_full_unstemmed Total Synthesis of the Antimitotic Marine Macrolide (−)-Leiodermatolide**
title_short Total Synthesis of the Antimitotic Marine Macrolide (−)-Leiodermatolide**
title_sort total synthesis of the antimitotic marine macrolide (−)-leiodermatolide**
topic Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4499261/
https://www.ncbi.nlm.nih.gov/pubmed/24481746
http://dx.doi.org/10.1002/anie.201310164
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