RESUMO
6-O-dodecanoyl-2-O-α-D-glucopyranosyl-L-ascorbic acid (6-sDode-AA-2G) was synthesized from 2-O-α-D-glucopyranosyl-L-ascorbic acid and vinyl laurate with a protease from Bacillus subtilis in 30% dimethylformamide (DMF)/dioxane with a low water content. The addition of 3% (v/v) water to DMF/dioxane dramatically enhanced the 6-sDode-AA-2G synthesis. The optimum reaction conditions enabled 6-sDode-AA-2G to be synthesized in a yield of 38.1%.
Assuntos
Ácido Ascórbico/análogos & derivados , Endopeptidases/metabolismo , Acilação , Ácido Ascórbico/química , Bacillus subtilis/enzimologia , Catálise , Dimetilformamida , Dioxanos , Endopeptidases/química , Microbiologia Industrial/métodos , Solventes , ÁguaRESUMO
A stable ascorbic acid derivative, 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G), exhibits vitamin C activity in vitro and in vivo after enzymatic hydrolysis to ascorbic acid. AA-2G has been approved by the Japanese Government as a quasi-drug principal ingredient in skin care and as a food additive. In order to achieve efficient action as an ascorbic acid source, a pro-vitamin C agent, on a variety of cells or tissues, we have synthesized a series of monoacyl AA-2G derivatives. Our previous studies indicate that a series of the derivatives is a readily available source of AA activity in vitro and in vivo, and suggested that intramolecular acyl migration of the derivatives might have occurred in a neutral aqueous solution. In this study, intramolecular acyl migration and enzymatic hydrolysis of a monoacyl AA-2G derivative, 6-O-dodecanoyl-2-O-alpha-D-glucopyranosyl-L-ascorbic acid (6-sDode-AA-2G), were investigated. 6-sDode-AA-2G underwent an intramolecular acyl migration to yield ca. 10% of an isomer in neutral aqueous solutions, and the acyl-migrated isomer was isolated and characterized as 5-O-dodecanoyl-2-O-alpha-D-glucopyranosyl-L-ascorbic acid (5-sDode-AA-2G). In some tissue homogenates from guinea pigs as well as in neutral aqueous solutions, 6-sDode-AA-2G underwent partial acyl migration to give 5-sDode-AA-2G. 6-sDode-AA-2G and the resulting 5-sDode-AA-2G were predominantly hydrolyzed with esterase to AA-2G and then with alpha-glucosidase to ascorbic acid in the tissue homogenates. The results will provide a further basis for its use as an ingredient in skin care, as an effective pharmacological agent and as a promising food additive.
Assuntos
Ácido Ascórbico/análogos & derivados , Ácido Ascórbico/metabolismo , Animais , Ácido Ascórbico/química , Esterases/metabolismo , Cobaias , Hidrólise , Masculino , alfa-Glucosidases/metabolismoRESUMO
2-O-alpha-D-Glucopyranosyl-L-ascorbic acid (AA-2G) laurate was synthesized from AA-2G and vinyl laurate with a protease from Bacillus subtilis in N,N-dimethylformamide (DMF) with low water content. Addition of water to DMF dramatically enhanced monoacyl AA-2G synthesis. Maximum synthetic activity was observed when 3% (v/v) water was added to the reaction medium. Under the optimal reaction conditions, 5-O-dodecanoyl-2-O-alpha-D-glucopyranosyl-L-ascorbic acid, 2-O-(6'-O-dodecanoyl-alpha-D-glucopyranosyl)-L-ascorbic acid, and 6-O-dodecanoyl-2-O-alpha-D-glucopyranosyl-L-ascorbic acid were synthesized in yields of 5.5%, 3.2%, and 20.4%, respectively.