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Synthesis and Neuroprotective Action of Optically Pure Neoechinulin A and Its Analogs
We developed an efficient, stereoselective synthetic method for the diketopiperazine moiety of neoechinulin A and its derivatives. The intramolecular cyclization at 80 ºC proceeded with minimal racemization of the stereogenic center at C-12 on neoechinulin A, even though the cyclization at 110 ºC ca...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Molecular Diversity Preservation International
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4034020/ https://www.ncbi.nlm.nih.gov/pubmed/27713287 http://dx.doi.org/10.3390/ph3041063 |
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author | Aoki, Toshiaki Ohnishi, Kensuke Kimoto, Masaaki Fujieda, Satoshi Kuramochi, Kouji Takeuchi, Toshifumi Nakazaki, Atsuo Watanabe, Nobuo Sugawara, Fumio Arai, Takao Kobayashi, Susumu |
author_facet | Aoki, Toshiaki Ohnishi, Kensuke Kimoto, Masaaki Fujieda, Satoshi Kuramochi, Kouji Takeuchi, Toshifumi Nakazaki, Atsuo Watanabe, Nobuo Sugawara, Fumio Arai, Takao Kobayashi, Susumu |
author_sort | Aoki, Toshiaki |
collection | PubMed |
description | We developed an efficient, stereoselective synthetic method for the diketopiperazine moiety of neoechinulin A and its derivatives. The intramolecular cyclization at 80 ºC proceeded with minimal racemization of the stereogenic center at C-12 on neoechinulin A, even though the cyclization at 110 ºC caused partial racemization. In contrast with these results, the cyclization on diketopiperazine of 8,9-dihydroneoechinulin A derivatives did not cause epimerization of the stereogenic centers, even at 110 °C. We examined the structure-activity relationships for the cytoprotective activity against cytotoxicity induced by 3-morpholinosydnonimine (SIN-1) in nerve growth factor (NGF)-differentiated PC12 cells. The C-8/C-9 double bond, but not the stereogenic center derived from alanine, was found to play a key role in the cytoprotective activity. |
format | Online Article Text |
id | pubmed-4034020 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Molecular Diversity Preservation International |
record_format | MEDLINE/PubMed |
spelling | pubmed-40340202014-05-27 Synthesis and Neuroprotective Action of Optically Pure Neoechinulin A and Its Analogs Aoki, Toshiaki Ohnishi, Kensuke Kimoto, Masaaki Fujieda, Satoshi Kuramochi, Kouji Takeuchi, Toshifumi Nakazaki, Atsuo Watanabe, Nobuo Sugawara, Fumio Arai, Takao Kobayashi, Susumu Pharmaceuticals (Basel) Article We developed an efficient, stereoselective synthetic method for the diketopiperazine moiety of neoechinulin A and its derivatives. The intramolecular cyclization at 80 ºC proceeded with minimal racemization of the stereogenic center at C-12 on neoechinulin A, even though the cyclization at 110 ºC caused partial racemization. In contrast with these results, the cyclization on diketopiperazine of 8,9-dihydroneoechinulin A derivatives did not cause epimerization of the stereogenic centers, even at 110 °C. We examined the structure-activity relationships for the cytoprotective activity against cytotoxicity induced by 3-morpholinosydnonimine (SIN-1) in nerve growth factor (NGF)-differentiated PC12 cells. The C-8/C-9 double bond, but not the stereogenic center derived from alanine, was found to play a key role in the cytoprotective activity. Molecular Diversity Preservation International 2010-03-31 /pmc/articles/PMC4034020/ /pubmed/27713287 http://dx.doi.org/10.3390/ph3041063 Text en © 2010 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Aoki, Toshiaki Ohnishi, Kensuke Kimoto, Masaaki Fujieda, Satoshi Kuramochi, Kouji Takeuchi, Toshifumi Nakazaki, Atsuo Watanabe, Nobuo Sugawara, Fumio Arai, Takao Kobayashi, Susumu Synthesis and Neuroprotective Action of Optically Pure Neoechinulin A and Its Analogs |
title |
Synthesis and Neuroprotective Action of Optically Pure Neoechinulin A and Its Analogs |
title_full |
Synthesis and Neuroprotective Action of Optically Pure Neoechinulin A and Its Analogs |
title_fullStr |
Synthesis and Neuroprotective Action of Optically Pure Neoechinulin A and Its Analogs |
title_full_unstemmed |
Synthesis and Neuroprotective Action of Optically Pure Neoechinulin A and Its Analogs |
title_short |
Synthesis and Neuroprotective Action of Optically Pure Neoechinulin A and Its Analogs |
title_sort | synthesis and neuroprotective action of optically pure neoechinulin a and its analogs |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4034020/ https://www.ncbi.nlm.nih.gov/pubmed/27713287 http://dx.doi.org/10.3390/ph3041063 |
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