Synthesis of Ellagic Acid O-Alkyl Derivatives and Isolation of Ellagic Acid as a Tetrahexanoyl Derivative from Fragaria ananassa

• Published in: Journal of natural products (Washington, D.C.) Vol. 55; no. 10; pp. 1402 - 1407
• Main Authors: Heur, Young-Hun, Zeng, Wenguang, Stoner, Gary D, Nemeth, Gregory A, Hilton, Bruce
• Format: Journal Article
• Language: English
• Published: CINCINNATI American Chemical Society 01.10.1992; AMER SOC PHARMACOGNOSY; American Society of Pharmacognosy
• Subjects: Animals; Antineoplastic Agents, Phytogenic - chemical synthesis; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - therapeutic use; Biological and medical sciences; Chemistry, Medicinal; Ellagic Acid - analogs & derivatives; Ellagic Acid - chemical synthesis; Ellagic Acid - therapeutic use; General pharmacology; Life Sciences & Biomedicine; Lung Neoplasms - drug therapy; Magnetic Resonance Spectroscopy; Mass Spectrometry; Medical sciences; Mice; Mice, Inbred A; Pharmacognosy. Homeopathy. Health food; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Plant Extracts - chemistry; Plant Extracts - therapeutic use; Plant Sciences; Science & Technology; CULTURED RAT; INHIBITION; MOUSE; Fragaria; Molecular structure; Pharmacognosy; Dicotyledones; Angiospermae; Rosaceae; Plant origin; Isolation; Spermatophyta; Anticarcinogen; Medicinal plant
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np50088a003

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 C-13 and H-1 nmr and ms. The C-14-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.