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 journalArticlepeer-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 languageEnglish
Pages (from-to)1063-1069
Number of pages7
JournalPharmaceuticals
Volume3
Issue number4
DOIs
Publication statusPublished - 2010

Keywords

  • Cytoprotective activity
  • Intramolecular cyclization
  • Neoechinulin A

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science

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