Studies on Hydroxy- Citric AcidLactones-Synthesis of Chiral Pyrrolidines

Abstract

(2S, 3s) and (2S,3R)-tetrahyclro-3-hydroxy-5-oxo-2,3-furandicarboxylic acids (Garcinia and Hibiscus acids), two less known less studied optically active hydroxyl acid lactones have been used fclr the syntheses of rare and novel 3 and 3,4- disubstituted chiral pyrrolidines , reserve for several pyrrolidine based natural products. While Garcinia acid with alkyl amines forms novel 3,4-disubstituted pyrrolidinediones its diastereomer Hibiscus acid failed to form 3,4-trans fused five membered rings. 3-substituted pyrrolidinediones were obtained in large amount from the di and triesters of Garcinia acid and the diester of Hibiscus acid. Novel 3- substituted pyrrolidinediones, sy5:tems capable of forming C2 symmetric supramolecular entities, were also obtained from the triesters of (+) and (-) -2- hydroxycitric acids. The pyrrolidiriedione, [(3aS,6aS)-512-(3,4-dimethoxyphenyl) ethyl]-3a-hydroxydihydro-2H-furo[2,3~~c]pyrrole-2,4,6[3H,5H]-trione], obtained from Garcinia acid has been ultimately identified as an analogue of mescaline isocitrimide lactone, a psychotropic bioprinciple obtained from an endangered cactus species, Mescal. Garcinia and Hibiscus acids and related (3aS, 6aS)-3a-(acetyloxy) dihydro- 5-(phenylmethy1)-6H- furo[2,3-c] pyrrole-2,4,6 (3H,4H)-trione and Methyl (2s)-, [2(3S~lp-methoxybenzyl-3-hydroxy-2-5-clioxotet~-l H-pyrrol-3-yl]-2-hydroxyethanoate synthesized for the first time have been subjected to a systematic VCD analysis for establishing the absolute configuration as it is necessary to understand and fine tune the mechanism of interaction of these molecules in solution state in the fat metabolism pathway. For the first time the absolute configuration of Garcinia and Hibiscus acids have been verified with VCD. The conformation sub population of Garcinia acid varies with solvents as revealed by the spectral behaviour of the same in DMSO and acetonitrile. Nevertheless, peak to peak comparison with the calculated spectrum helps to assign the absolute configuration as ;lS,3S.