Pharmaceuticals 2010, 3(4), 1063-1069; doi:10.3390/ph3041063
Article

Synthesis and Neuroprotective Action of Optically Pure Neoechinulin A and Its Analogs

1 Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan 2 Genome and Drug Discovery Center, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan 3 Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan
* Author to whom correspondence should be addressed.
Received: 21 December 2009; in revised form: 5 January 2010 / Accepted: 29 March 2010 / Published: 31 March 2010
(This article belongs to the Special Issue Asymmetric Synthesis and Medicinal Chemistry)
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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 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.
Keywords: neoechinulin A; intramolecular cyclization; cytoprotective activity

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MDPI and ACS Style

Aoki, T.; Ohnishi, K.; Kimoto, M.; Fujieda, S.; Kuramochi, K.; Takeuchi, T.; Nakazaki, A.; Watanabe, N.; Sugawara, F.; Arai, T.; Kobayashi, S. Synthesis and Neuroprotective Action of Optically Pure Neoechinulin A and Its Analogs. Pharmaceuticals 2010, 3, 1063-1069.

AMA Style

Aoki T, Ohnishi K, Kimoto M, Fujieda S, Kuramochi K, Takeuchi T, Nakazaki A, Watanabe N, Sugawara F, Arai T, Kobayashi S. Synthesis and Neuroprotective Action of Optically Pure Neoechinulin A and Its Analogs. Pharmaceuticals. 2010; 3(4):1063-1069.

Chicago/Turabian Style

Aoki, Toshiaki; Ohnishi, Kensuke; Kimoto, Masaaki; Fujieda, Satoshi; Kuramochi, Kouji; Takeuchi, Toshifumi; Nakazaki, Atsuo; Watanabe, Nobuo; Sugawara, Fumio; Arai, Takao; Kobayashi, Susumu. 2010. "Synthesis and Neuroprotective Action of Optically Pure Neoechinulin A and Its Analogs." Pharmaceuticals 3, no. 4: 1063-1069.

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