Carbohydrate esters enzymatic synthesis

In the pharmaceutieal area, the reaction of oleic acid catalyzed by lipase is used for the production of monoolein and carbohydrate fatty aeid esters, compounds with emulsifiers and surfactant properties (Wang et al., 2013 Abdulmalek et al., 2012). Another important surfactant produced is the fatty acid ester of vitamin C (Stojanovic et al., 2013). Enzymatic synthesis of aseorbyloleate is very attractive, as well as surfactants, which have high antioxidant potential (Viklrmd Alander Hult, 2003). Due to biological... 

Efficient enzymatic conversion can be achieved even though most of the reactants are present as solids, provided that there is a liquid phase in which the reaction can occur. This approach has been successfully used for carbohydrate ester synthesis with synthesis of glucose esters of fatty acids between C12 and C18 as typical examples [34]. It is important that the substrates dissolve during the reaction, and often the products precipitate as they are formed, which can be an advantage due to a favourable effect on the equilibrium position. Candida antarctica lipase B is an efficient catalyst in this system and solvents used (in moderate amounts) include ethyl methyl ketone, acetone or dioxane. In order to increase the ester yield, water formed in the reaction can be removed by azeotropic distillation and the solvent (e.g. ethyl metyl ketone) can after condensation be dried by pervaporation, giving a practically useful complete process [35]. 

Janssen, A. E. M., Klabbers, C., Franssen, M. C. R. and Vantriet, K. (1991) Enzymatic-synthesis of carbohydrate esters in 2-p5urolidone. Enzyme Microb. Technol., 13, 565-572. Inada, Y., Nishimura, H., Takahashi, K. et al. (1984) Ester synthesis catalysed by polyethylene glycol-modified lipase in benzene. Biochem. Biophys. Res. Commim., 122, 845-850. 

Seino, H., T. Uchibori, T. Nishitani, S. Inama.su, Enzymatic synthesis of carbohydrate esters of fatty acid. I Esterification of sucrose, glucose, fructose and sorbitol,/. Am. Oil Chem. Soc., 1984,6/, 1761-1765. 

Much of the chemistry of monosaccharides is the familiar chemistry of alcohols and aldehydes/ketones. Thus, the hydroxyl groups of carbohydrates form esters and ethers. The carbonyl group of a monosaccharide can be reduced with NaBH4 to form an alditol, oxidized with aqueous Br2 to form an aldonic acid, oxidized with HNO3 to form an aldaric acid, oxidized enzymatically to form a uronic acid, or treated with an alcohol in the presence of acid to form a glycoside. Monosaccharides can also be chain-lengthened by the multistep Kiliani-Fischer synthesis and can be chain-shortened by the Wohl degradation. 

Surprisingly, the introduction of the pyridine ring not only influences the velocity of the enzymatic transformations, but also induces promising stereochemical effects (Table 1). For instance, at 40% conversion (R)-phenylethanol is obtained from the pyridyl acetate 25 with 73 % ee, whereas the value for the corresponding phenylacetate is only 28%. Also, the secondary alcohol liberated from the ester 26 displays 98% ee at 40% conversion, whereas the respective phenylacetate leads to 1-phenylpropanol with 94% ee but at a conversion rate of 12% only [19,20]. These results demonstrate that the stereoselecting properties of penicillin acylase may be enhanced by appropriate engineering of the substrate. This is of particular interest since this enzyme has already been used for the kinetic resolution of various chiral alcohols [21-24], e.g. furyl alkyl carbinols [24], which are valuable precursors for the de novo synthesis, with moderate to high ee values, of carbohydrates. 

Several improvements of the process, such as the reaction with acyl chlorides or the application of two-phase reaction systems with propylene glycol and an emulsifier in order to build a microemulsion, have been described in the literature and patents [21]. Another approach for the synthesis of sugar esters is the use of enzymes. Enzymatic catalysis in the field of carbohydrate chemistry has been actively explored over years in laboratory... 

Most studies of enzymatic sugar ester synthesis have focused on the esterification of monosaccharides, since the problems with poor substrate miscibility increase significantly with increasing size of the carbohydrate. However, by careful choice of reaction conditions it has been shown possible to acylate several di- and trisaccharides efficiently. Solvent mixtures of 2-methyl-2-butanol and dimethylsulfoxide have thus been used in... 

Ionic liquids are promising nonaqueous solvents for the dissolution of carbohydrates and they have been used in several studies on enzymatic sugar ester synthesis. Candida antarctica lipase B was the best enzyme for synthesis of glucose esters in a two-phase system containing an ionic liquid and rm-butanol [31]. Recently, the use of supersaturated sugar solutions [32] and ultrasonic treatment [33] has been reported to make sugar ester synthesis in ionic liquids even more efficient. 

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