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 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.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.|Genome and Drug Discovery Center, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Aoki
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.|Genome and Drug Discovery Center, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Ohnishi
authors.affiliation: Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kimoto
authors.affiliation: Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujieda
authors.affiliation: Genome and Drug Discovery Center, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.|Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Kuramochi
authors.affiliation: Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Takeuchi
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Nakazaki
authors.affiliation: Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Watanabe
authors.affiliation: Genome and Drug Discovery Center, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.|Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Sugawara
authors.affiliation: Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Arai
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. kobayash@rs.noda.tus.ac.jp.|Genome and Drug Discovery Center, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. kobayash@rs.noda.tus.ac.jp.
authors.forename: Susumu
authors.initials: S
authors.lastname: Kobayashi
keywords: cytoprotective activity; intramolecular cyclization; neoechinulin A