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Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs
Herein, we report the enantiospecific synthesis of two artificial glutamate analogs designed based on IKM-159, an antagonist selective to the AMPA-type ionotropic glutamate receptor. The synthesis features the chiral resolution of the carboxylic acid intermediate by the esterification with ʟ-menthol...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Beilstein-Institut
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934734/ https://www.ncbi.nlm.nih.gov/pubmed/33727977 http://dx.doi.org/10.3762/bjoc.17.48 |
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author | Morokuma, Kenji Tsukamoto, Shuntaro Mori, Kyosuke Miyako, Kei Sakai, Ryuichi Irie, Raku Oikawa, Masato |
author_facet | Morokuma, Kenji Tsukamoto, Shuntaro Mori, Kyosuke Miyako, Kei Sakai, Ryuichi Irie, Raku Oikawa, Masato |
author_sort | Morokuma, Kenji |
collection | PubMed |
description | Herein, we report the enantiospecific synthesis of two artificial glutamate analogs designed based on IKM-159, an antagonist selective to the AMPA-type ionotropic glutamate receptor. The synthesis features the chiral resolution of the carboxylic acid intermediate by the esterification with ʟ-menthol, followed by a configurational analysis by NMR, conformational calculation, and X-ray crystallography. A mice in vivo assay showed that (2R)-MC-27, with a six-membered oxacycle, is neuroactive, whereas the (2S)-counterpart is inactive. It was also found that TKM-38, with an eight-membered azacycle, is neuronally inactive, showing that the activity is controlled by the ring C. |
format | Online Article Text |
id | pubmed-7934734 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Beilstein-Institut |
record_format | MEDLINE/PubMed |
spelling | pubmed-79347342021-03-15 Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs Morokuma, Kenji Tsukamoto, Shuntaro Mori, Kyosuke Miyako, Kei Sakai, Ryuichi Irie, Raku Oikawa, Masato Beilstein J Org Chem Full Research Paper Herein, we report the enantiospecific synthesis of two artificial glutamate analogs designed based on IKM-159, an antagonist selective to the AMPA-type ionotropic glutamate receptor. The synthesis features the chiral resolution of the carboxylic acid intermediate by the esterification with ʟ-menthol, followed by a configurational analysis by NMR, conformational calculation, and X-ray crystallography. A mice in vivo assay showed that (2R)-MC-27, with a six-membered oxacycle, is neuroactive, whereas the (2S)-counterpart is inactive. It was also found that TKM-38, with an eight-membered azacycle, is neuronally inactive, showing that the activity is controlled by the ring C. Beilstein-Institut 2021-02-24 /pmc/articles/PMC7934734/ /pubmed/33727977 http://dx.doi.org/10.3762/bjoc.17.48 Text en Copyright © 2021, Morokuma et al. https://creativecommons.org/licenses/by/4.0https://www.beilstein-journals.org/bjoc/terms/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 author(s) and source are credited and that individual graphics may be subject to special legal provisions. The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: (https://www.beilstein-journals.org/bjoc/terms/terms) |
spellingShingle | Full Research Paper Morokuma, Kenji Tsukamoto, Shuntaro Mori, Kyosuke Miyako, Kei Sakai, Ryuichi Irie, Raku Oikawa, Masato Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs |
title | Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs |
title_full | Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs |
title_fullStr | Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs |
title_full_unstemmed | Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs |
title_short | Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs |
title_sort | menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs |
topic | Full Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934734/ https://www.ncbi.nlm.nih.gov/pubmed/33727977 http://dx.doi.org/10.3762/bjoc.17.48 |
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