Synthesis of ellagic acid O-alkyl derivatives and isolation of ellagic acid as a tetrahexanoyl derivative from Fragaria ananassa.
Ellagic acid [1] is a gallic acid dimer that occurs in plants, fruits, and nuts, either in its free form, or in a series of ellagitannins, or as a glucoside. It has been shown to inhibit cancer induced by several types of chemical carcinogens including polycyclic aromatic hydrocarbons, N-nitrosamines, aflatoxin, and aromatic amines. It has been extracted from a number of fruits, including strawberries; however, its presence in the extracts was determined only by hplc connected with a diode array detector. In the present report, ellagic acid was isolated as a tetrahexanoyl derivative 2 from Fragaria ananassa and identified by 13C and 1H nmr and ms. The 13C-nmr shifts of the aromatic carbons adjacent to a hexanoyloxy group were assigned using two new synthetic model compounds: 3,3'-dihexanoyloxydiphenic-2,2',6,6'-dilactone [3] and 4,4'-dihexanoyloxydiphenic-2,2',6,6'-dilactone [4]. Two new derivatives of ellagic acid [1],3,3'-di-beta-D-glucopyranosylellagic acid decaacetate [5] and 3,3'-di-n-octyl-4,4'-dihexanoylellagic acid [7], were also synthesized. Both derivatives were less effective as inhibitors of benzo[a]pyrene tumorigenesis in the lungs of strain A/J mice than ellagic acid.
Heur
Y H
YH
Department of Pathology, Medical College of Ohio, Toledo 43614.
Zeng
W
W
Stoner
G D
GD
Nemeth
G A
GA
Hilton
B
B
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000302:isolation & purification / Q000627:therapeutic use; D004610:Ellagic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D008805:Mice, Inbred A; D010936:Plant Extracts / Q000737:chemistry* / Q000627:therapeutic use
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D004610:Ellagic Acid