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Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry

The regioselective difunctionalization of cyclodextrins (CDs) leading to derivatives amenable to further transformations is a daunting task due to challenging purification and unambiguous characterization of the obtained regioisomers with similar physicochemical properties. The primary-side homo-dif...

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Autores principales: Benkovics, Gábor, Bálint, Mihály, Fenyvesi, Éva, Varga, Erzsébet, Béni, Szabolcs, Yannakopoulou, Konstantina, Malanga, Milo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Beilstein-Institut 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444459/
https://www.ncbi.nlm.nih.gov/pubmed/30992718
http://dx.doi.org/10.3762/bjoc.15.66
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author Benkovics, Gábor
Bálint, Mihály
Fenyvesi, Éva
Varga, Erzsébet
Béni, Szabolcs
Yannakopoulou, Konstantina
Malanga, Milo
author_facet Benkovics, Gábor
Bálint, Mihály
Fenyvesi, Éva
Varga, Erzsébet
Béni, Szabolcs
Yannakopoulou, Konstantina
Malanga, Milo
author_sort Benkovics, Gábor
collection PubMed
description The regioselective difunctionalization of cyclodextrins (CDs) leading to derivatives amenable to further transformations is a daunting task due to challenging purification and unambiguous characterization of the obtained regioisomers with similar physicochemical properties. The primary-side homo-difunctionalization of β-CD can lead to three regioisomers, while the hetero-difunctionalization can generate three pairs of pseudoenantiomers. Previously, approaches with several synthetic steps, expensive reagents, high purification demands and low yields of the products have been employed. Herein we present direct, short and efficient primary-side difunctionalization strategies featuring reproducibility, ease of product purification, scalability of the reactions and versatility of the substituents introduced. Specifically, the prepared ditosylated β-CDs were separated using preparative reversed-phase column chromatography and their structures were elucidated by NMR experiments. Azidation led to the corresponding pure diazido regioisomers. Direct monotosylation of 6-monoazido-β-CD or monoazidation of the single regioisomers 6(A),6(X)-ditosyl-β-CDs afforded hetero-difunctionalized 6(A)-monoazido-6(X)-tosyl-β-CDs in significant yields. Overall, the single regioisomers, 6(A),6(X)-ditosyl-, 6(A),6(X-)diazido- and 6(A)-monoazido-6(X)-monotosyl-β-CD were prepared in one or two steps and purified in multigram scale thus opening the way towards further selective and orthogonal functionalizations of β-CD hosts.
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spelling pubmed-64444592019-04-16 Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry Benkovics, Gábor Bálint, Mihály Fenyvesi, Éva Varga, Erzsébet Béni, Szabolcs Yannakopoulou, Konstantina Malanga, Milo Beilstein J Org Chem Full Research Paper The regioselective difunctionalization of cyclodextrins (CDs) leading to derivatives amenable to further transformations is a daunting task due to challenging purification and unambiguous characterization of the obtained regioisomers with similar physicochemical properties. The primary-side homo-difunctionalization of β-CD can lead to three regioisomers, while the hetero-difunctionalization can generate three pairs of pseudoenantiomers. Previously, approaches with several synthetic steps, expensive reagents, high purification demands and low yields of the products have been employed. Herein we present direct, short and efficient primary-side difunctionalization strategies featuring reproducibility, ease of product purification, scalability of the reactions and versatility of the substituents introduced. Specifically, the prepared ditosylated β-CDs were separated using preparative reversed-phase column chromatography and their structures were elucidated by NMR experiments. Azidation led to the corresponding pure diazido regioisomers. Direct monotosylation of 6-monoazido-β-CD or monoazidation of the single regioisomers 6(A),6(X)-ditosyl-β-CDs afforded hetero-difunctionalized 6(A)-monoazido-6(X)-tosyl-β-CDs in significant yields. Overall, the single regioisomers, 6(A),6(X)-ditosyl-, 6(A),6(X-)diazido- and 6(A)-monoazido-6(X)-monotosyl-β-CD were prepared in one or two steps and purified in multigram scale thus opening the way towards further selective and orthogonal functionalizations of β-CD hosts. Beilstein-Institut 2019-03-18 /pmc/articles/PMC6444459/ /pubmed/30992718 http://dx.doi.org/10.3762/bjoc.15.66 Text en Copyright © 2019, Benkovics et al. https://creativecommons.org/licenses/by/4.0https://www.beilstein-journals.org/bjoc/termsThis is an Open Access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0). Please note that the reuse, redistribution and reproduction in particular requires that the authors and source are credited. The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: (https://www.beilstein-journals.org/bjoc/terms)
spellingShingle Full Research Paper
Benkovics, Gábor
Bálint, Mihály
Fenyvesi, Éva
Varga, Erzsébet
Béni, Szabolcs
Yannakopoulou, Konstantina
Malanga, Milo
Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry
title Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry
title_full Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry
title_fullStr Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry
title_full_unstemmed Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry
title_short Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry
title_sort homo- and hetero-difunctionalized β-cyclodextrins: short direct synthesis in gram scale and analysis of regiochemistry
topic Full Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444459/
https://www.ncbi.nlm.nih.gov/pubmed/30992718
http://dx.doi.org/10.3762/bjoc.15.66
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