Synthetic Studies and Biological Activity of Some Pyrrolidinone Type Compounds

Author

ZURINA SHAAMERI & A HMAD SAZALI HAMZAH

Proceeding

The 21st Annual Seminar of the Malaysian Natural Product Society.(Herbal Medicine:Natural Products Society), Palm Garden, Putrajaya Malaysia.

Date

22/11/2005

Keyword

3-hydroxy-4-methylproline, ß,ß-diketoester, pyrrolidinone

Abstract

Naturally occurring amino acids containing 3-hydroxy-4-methylproline (Hmp) moiety have been extensively studied due to their unique structures and diverse bioactivities.  Such fine chemicals include proteasome inhibitor lactacystin (Streptomyces sp.), marine neurotoxin janolusimide (Janolus sp.), hypertensive antibiotic codonopsinine (Codonopsis sp.) and antifungal agent echinocandin (Aspergillus sp.). In the development towards the synthesis of Hmp, a key intermediateβ,β-diketoester, has been utilized in various asymmetric syntheses in generating over 40 novel compounds containing a pyrrolidinone ring moiety, in good to moderate yields.  Four compounds were found to exhibit neuroprotective ability via the hydrogen peroxide oxidative stress-induced model.  The synthetic work on the assembly of these pyrrolidinone type target molecules such as janolusimide and codonopsinine is currently being investigated in our laboratory.