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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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Detalles Bibliográficos
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
Descripción
Sumario: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.