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

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

7 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
Externally published	Yes

Keywords

Cytoprotective activity
Intramolecular cyclization
Neoechinulin A

ASJC Scopus subject areas

Molecular Medicine
Pharmaceutical Science

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10.3390/ph3041063

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title = "Synthesis and neuroprotective action of optically pure neoechinulin A and its analogs",

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.",

keywords = "Cytoprotective activity, Intramolecular cyclization, Neoechinulin A",

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

year = "2010",

doi = "10.3390/ph3041063",

language = "English",

volume = "3",

pages = "1063--1069",

journal = "Pharmaceuticals",

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TY - JOUR

T1 - Synthesis and neuroprotective action of optically pure neoechinulin A and its analogs

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

Y1 - 2010

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.

KW - Cytoprotective activity

KW - Intramolecular cyclization

KW - Neoechinulin A

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U2 - 10.3390/ph3041063

DO - 10.3390/ph3041063

M3 - Article

AN - SCOPUS:77952113759

VL - 3

SP - 1063

EP - 1069

JO - Pharmaceuticals

JF - Pharmaceuticals

SN - 1424-8247

IS - 4

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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