Synthesis and neuroprotective action of optically pure neoechinulin A and its analogs

Toshiaki Aoki; Kensuke Ohnishi; Masaaki Kimoto; Satoshi Fujieda; Kouji Kuramochi; Toshifumi Takeuchi; Atsuo Nakazaki; Nobuo Watanabe; Fumio Sugawara; Takao Arai; Susumu Kobayashi

doi:10.3390/ph3041063

Synthesis and neuroprotective action of optically pure neoechinulin A and its analogs

Toshiaki Aoki, Kensuke Ohnishi, Masaaki Kimoto, Satoshi Fujieda, Kouji Kuramochi, Toshifumi Takeuchi, Atsuo Nakazaki, Nobuo Watanabe, Fumio Sugawara, Takao Arai, Susumu Kobayashi

MED - Medical Sciences

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

Abstract

We developed an efficient, stereoselective synthetic method for the diketopiperazine moiety of neoechinulin A and its derivatives. The intramolecular cyclization at 80 °C proceeded with minimal racemization of the stereogenic center at C-12 on neoechinulin A, even though the cyclization at 110 °C 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.

Original language	English
Pages (from-to)	1063-1069
Number of pages	7
Journal	Pharmaceuticals
Volume	3
Issue number	4
DOIs	https://doi.org/10.3390/ph3041063
Publication status	Published - 2010

Keywords

Cytoprotective activity
Intramolecular cyclization
Neoechinulin A

ASJC Scopus subject areas

Molecular Medicine
Pharmaceutical Science

Access to Document

10.3390/ph3041063

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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.

In: Pharmaceuticals, Vol. 3, No. 4, 2010, p. 1063-1069.

Research output: Contribution to journal › Article › peer-review

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abstract = "We developed an efficient, stereoselective synthetic method for the diketopiperazine moiety of neoechinulin A and its derivatives. The intramolecular cyclization at 80 °C proceeded with minimal racemization of the stereogenic center at C-12 on neoechinulin A, even though the cyclization at 110 °C 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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AU - Aoki, Toshiaki

AU - Ohnishi, Kensuke

AU - Kimoto, Masaaki

AU - Fujieda, Satoshi

AU - Kuramochi, Kouji

AU - Takeuchi, Toshifumi

AU - Nakazaki, Atsuo

AU - Watanabe, Nobuo

AU - Sugawara, Fumio

AU - Arai, Takao

AU - Kobayashi, Susumu

PY - 2010

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N2 - We developed an efficient, stereoselective synthetic method for the diketopiperazine moiety of neoechinulin A and its derivatives. The intramolecular cyclization at 80 °C proceeded with minimal racemization of the stereogenic center at C-12 on neoechinulin A, even though the cyclization at 110 °C 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.

AB - We developed an efficient, stereoselective synthetic method for the diketopiperazine moiety of neoechinulin A and its derivatives. The intramolecular cyclization at 80 °C proceeded with minimal racemization of the stereogenic center at C-12 on neoechinulin A, even though the cyclization at 110 °C 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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