Sugar fatty acid esters synthesis

A comparison of the synthesis of Z-Phe-Leu-NH2 in ten different solvents revealed that the highest overall yields could be expected in solvents where the substrate solubility is minimized. The highest yields in terms of solid product were found in solvents where both substrate and product solubility are minimized [45]. These simple rules may not hold when special factors apply, such as the formation of solid solvates. This may account for a few apparent exceptions, such as the product precipitation in dichloromethane of both a peptide and a sugar fatty acid ester [45, 63]. 

Yan, Y., U.T. Bornscheuer, L. Cao, and R.D. Schmid, Lipase-Catalyzed Solid-Phase Synthesis of Sugar Fatty Acid Esters. Removal of By-Products by Azeotropic Distillation, Enzyme Microb. Technol. 25 725-728 (1999). 

Sarney, D.B. Vulfson, E.N. Enzymatic synthesis of sugar fatty acid esters in solvent-free media. In Enzymes in Nonaqueous Solvents Methods and Protocols (Methods in Biotechnology Vol. 15) Vulfson, E.N., Hailing, P.J., Holland, H.L., Eds. Humana Press Totawa, 2001 531-543. 

Cao, L., Fischer, A., Bomscheuer, U. T., and Schmid, R. D., Lipase-catalyzed sohd phase synthesis of sugar fatty acid esters. Biocat. Biotrans., 14 269-283, 1997. 

Cao L, Eischer A, Bornscheuer UT et al. (1997) Lipase-catalysed solid phase synthesis of sugar fatty acid esters. Biocatal Biotransfor 14 269-283 Cao L, van Langen L, Sheldon, R (2(X)3) Immobilised enzymes carrier-bound or carrier-free Curr Opin Biotechnol 14 1-8... 

The synthesis of sugar fatty acid esters has recently been described in several reviews [1-6]. In the following section, we highlight recent trends and provide a brief historical overview of the production of sugar fatty acid esters with particular emphasis on the sucrose esters. 

B. Chemical Synthesis of Sugar Fatty Acid Esters... 

The enzymatic synthesis of sugar fatty acid esters has been reviewed in recent times [2,6,32]. The biocatalytic properties of lipases and the basic principles governing lipase-catalyzed esterification have been described in the... 

Enzymatic solvent-free synthesis of sugar fatty acid esters was first reported by Adelhorst et al. [32] who performed regioselective acylation of... 

Fregapane, G., Sarney, D. B., and Vulfson, E. N., Enzymic solvent-free synthesis of sugar acetal fatty acid esters. Enzyme Microb. Technol., 13, 796-800, 1991. 

Eerrer P, Montesinos JL, Valero E et al. (2001) Production of native and recombinant lipases by Candida rugosa a review. Appl Biochem Biotechnol 95 221—255 Fregapane G, Samey DB, Vulfson EN (1991) Enzymic solvent-free synthesis of sugar acetal fatty acid esters. Enzyme Microb Technol 13(10) 796-800 Fuenzalida M, Markovits A, Martinez I (2006) Process for producing sterol or stand esters by enzymatic transesterification in solvent and water free media. EP 1285969 Bl. Issued on November 10, 2006... 

SCHEME 1 Ryoto sugar ester synthesis is based on transesteriiication of sucrose with a methyl fatty acid ester under conditions in which methanol is continuously removed. The product includes a complex mixture of K-soaps, diesters and mono-/ diglycerides, as well as the sucrose monoester when produced from crude beef tallow. An excess of sucrose is required (3 mol) to enhance the yield of the monoester over higher substituted products. DMF must be recovered for economic operation and because of its toxicity. 

Typically, lipases are employed in esterification however, proteases have also been utilized in organic medium although their normal function is peptidic bond hydrolysis. Their action in ester bond formation is rationalized in terms of the similarity between the active center that is mechanistically essential for transesterification. Several lipases originating from various sources have been utilized in sugar fatty acid synthesis. The activity of these enzymes is highly dependent on the reaction conditions employed and whether they are used in the free state or immobilized on a support. Immobilization confers better homogeneity of the enzyme for reaction and promotes greater thermostability of the protein [30]. The prochiral selectivity and substrate preference of lipases and protease also depend on the solvent system [34,35]. 

Inositols, ie, hexaliydrobenzenehexols, are sugars that have received increasing study and are useful in the treatment of a wide variety of human disorders, including vascular disease, cancer, cirrhosis of the Hver, frostbite, and muscular dystrophy (269). Myoinositol esters prepared by reaction with lower fatty acid anhydrides are useful as Hver medicines and nonionic surfactants the aluminum and ammonium salts of inositol hexasulfate are useful anticancer agents (270). Tetraarjloxybenzoquinones are intermediates in the preparation of dioxazine dyes (266,271). The synthesis of hexakis(aryloxy)benzenes has also beenpubUshed (272). 

Once bearing some substituents, the decrease of polarity of the sucrose derivatives makes them soluble in less-polar solvents, such as acetone or tert-butanol, in which some lipases are able to catalyze esterifications. Unlike proteases, which necessitate most often the use of an activated acyl donor (such as vinyl or trifluoroethyl esters), lipases are active with simple esters and even the parent carboxylic acids in the presence of a water scavenger. The selectivity of the lipase-catalyzed second esterification is specific for OH-6 allowing the synthesis of mixed T,6 -diesters.123,124 For some lipases, a chain-length dependence on the regiochemistry was observed.125 Selectively substituted monoesters were thus prepared and studied for their solution and thermotropic behavior.126,127 Combinations of enzyme-mediated and purely chemical esterifications led to a series of specifically substituted sucrose fatty acid diesters with variations in the chain length, the level of saturation, and the position on the sugar backbone. This allowed the impact of structural variations on thermotropic properties to be demonstrated (compare Section III.l).128... 

The glycosidation of the reducing sugars obtained from hemicelluloses leads to the alkyl polypentosides surfactants. Glycosylation needs fatty alcohols as raw materials. Natural fatty alcohols derived, for example, from coconut or palm kernel oil are used in the alkyl polyglycoside synthesis to buUd up the hydrophobic part of the surfactants. These alcohols are used as blends obtained after transesterification and fractionation of oils leading to corresponding fatty acid methyl esters, and... 

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