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 |
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Pages (from-to) | 1063-1069 |
Number of pages | 7 |
Journal | Pharmaceuticals |
Volume | 3 |
Issue number | 4 |
DOIs | |
Publication status | Published - 2010 |
Externally published | Yes |
Keywords
- Cytoprotective activity
- Intramolecular cyclization
- Neoechinulin A
ASJC Scopus subject areas
- Molecular Medicine
- Pharmaceutical Science