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

Abstract

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.

Strategies to improve ellagic acid bioavailability: from natural or semisynthetic derivatives to nanotechnological approaches based on innovative carriers

“…These findings suggest that it is possible to deduce qualitative rules for predicting the activity of EA analogues, taking into account their chemical differences from the parental compound [67]. Conversely, two other semisynthetic derivatives, such as 3,3 ′ -di-beta-Dglucopyranosylellagic acid decaacetate and 3,3 ′ -di-n-octyl-4,4 ′ -dihexanoylellagic acid, were less effective than EA in inhibiting lung tumour formation after exposure of A/J mice to benzo[a]pyrene [68]. Interestingly, the peracetate derivative (3,4,3,4-tetra-O-acetylellagic acid) was more efficient than EA in protecting bone marrow and lungs from genotoxicity induced by aflatoxin B 1 [69].…”

Convenient Synthesis of Ellagic Acid from Methyl Gallate and SARS-CoV-2 3CLpro Antiviral Activity

“…Ellagic acid (1) is poorly soluble in water and organic solvents, because of this reason direct identification was complicated by this behavior. 19 The 1 H NMR of ellagic acid showed only one peak in the aromatic zone, confirming that ellagic acid is a symmetrical molecule. The NMR, IR and Rf data are agree with data of commercial sample purchased from Aldrich Chemicals and purified by crystallization from ethanol.…”

“…Ellagic acid ( 1 ) is poorly soluble in water and organic solvents; thus, direct identification was complicated by this behavior. 19…”