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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...

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Autores principales: Aoki, Toshiaki, Ohnishi, Kensuke, Kimoto, Masaaki, Fujieda, Satoshi, Kuramochi, Kouji, Takeuchi, Toshifumi, Nakazaki, Atsuo, Watanabe, Nobuo, Sugawara, Fumio, Arai, Takao, Kobayashi, Susumu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International 2010
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.
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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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