Next Article in Journal
Lessons Learned from Surveillance of Antimicrobial Susceptibilities of Pseudomonas aeruginosa at a Large Academic Medical Center
Previous Article in Journal
Cell-Penetrating Peptides: A Comparative Study on Lipid Affinity and Cargo Delivery Properties
Pharmaceuticals 2010, 3(4), 1063-1069; doi:10.3390/ph3041063

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

1,2, 1,2, 3, 3, 2,3, 3, 1, 3, 2,3, 3 and 1,2,*
Received: 21 December 2009 / Revised: 5 January 2010 / Accepted: 29 March 2010 / Published: 31 March 2010
(This article belongs to the Special Issue Asymmetric Synthesis and Medicinal Chemistry)
View Full-Text   |   Download PDF [207 KB, 1 April 2010; original version 31 March 2010]   |   Browse Figures


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 neoechinulin A; intramolecular cyclization; cytoprotective activity
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Share & Cite This Article

Further Mendeley | CiteULike
Export to BibTeX |
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.

View more citation formats

Related Articles

Article Metrics

For more information on the journal, click here


Cited By

[Return to top]
Pharmaceuticals EISSN 1424-8247 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert