Acylated sugars, lipase-catalyzed

In other reports, the lipase-catalyzed acylation of benzylidene derivatives of sugars, useful intermediates in the synthesis of oligosaccharides, has been described [42]. For example, the esterification of 4,6-O-benzylidene-a-D-glucopy-ranoside (13) with vinyl acetate by action of Pseudomonas cepacia lipase gave quantitatively the 2-O-acetate 13a. [42b] As a third case, it deserves to be mentioned the extensive work of Russo and coworkers for the chemo-enzymatic synthesis of milk oligosaccharides [43]. 

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 selective enzyme-catalyzed acylation of carbohydrates is of great interest, as of carbohydrates fatty acid esters of carbohydrates have important applications in detergents, cosmetics, foodstuff, and pharmaceuticals because of their surface-active properties. Monoacylated sugars have been synthesized by lipase-catalyzed transesterifications of activated esters in pyridine and by protease-catalyzed esterifications in DMF. A most remarkable new development... 

Most of lipase-catalyzed acylations of sugars in organic solvents have been reported as transesterification rather than esterification reactions. The displacement of the equilibrium towards products has been accomplished by using activated acyl donors [58] such as 2,2,2-trichloroethyl esters and, more often, enol esters. The use of enol esters, such as a vinyl or an isopropenyl ester, was, in fact, first reported in lipase-catalyzed reactions with sugars [59]. In the reaction, an unstable enol is liberated which instantaneously tautomerizes to the corresponding aldehyde or ketone, making the reaction irreversible. 

Ikeda, I. and Klibanov, A. M., Lipase-catalyzed acylation of sugars solubilized in hydrophobic solvents by complexation, Biotechnol. Bioeng., 42, 788-791, 1993. 

Selective Acylation of Sugar Derivatives Catalyzed by Immobilized Lipase... 

Lipase is an enzyme that catalyzes the hydrolysis of fatty acid esters normally in an aqueous environment in living systems. However, some isolated lipases are stable in organic solvents and can act as catalyst for reverse reactions, esterifications, and transesterifications (Scheme 1) in organic media [1-5]. So far, chiral drugs, liquid crystals, acylated sugar-based surfactants, and functional triglycerides have been synthesized through lipase catalysis [6-10]. 

Maugard, T., Remaud-Simeon, M., Petre, D. and Monsan, P. (1997) Lipase-catalyzed chemos-elective A-acylation of amino-sugar derivatives in hydrophobic solvent acid-amine ion-pair effects. Tetrahedron, 53, 7587-7594. 

Fatty acids of sugars are potentially useful and fully green nonionic surfactants, but the lipase-mediated esterification of carbohydrates is hampered by the low solubility of carbohydrates in reaction media that support lipase catalysis in general. Because the monoacylated product (Figure 10.8) is more soluble in traditional solvents than is the starting compound, the former tends to undergo further acylation into a diester. In contrast, the CaLB-catalyzed esterification of glucose with vinyl acetate in the ionic liquid [EMIm][BF4] was completely selective. The reaction became much faster and somewhat less selective when conducted in... 

It has also been shown that lipase CA can produce reduced sugar-containing polyesters regioselectively from divinyl sebacate and sorbitol, in which sorbitol was exclusively acylated at the 1 and 6-positions (Scheme 23.11) [115]. Mannitol and meso-erythritol were also regioselectively polymerized with divinyl sebacate. The lipase CA-catalyzed polycondensation of adipic acid and sorbitol also took place in... 

Therisod M, Klibanov AM (1987) Regioselective acylation of secondary hydroxy groups in sugars catalyzed by lipases in organic solvents. J Am Chem Soc 109 3977... 

Polar solvents have a log P < 2, moderate solvents have a log P in the range 2apolar solvents log P > 4 (Table 1). Synthesis is best achieved in solvents of intermediate polarity that are able to partially solubilize both the sugar and enzyme, or in solvents with a log P value greater than 1.5 that do not affect the hydration shell of the enzyme and so denature the protein. Tertiary alcohols are particularly effective solvents in this respect as they cannot react with lipases due to steric hindrance at the hydroxy group and their boiling points facilitate their removal after reaction. tert-Butyl alcohol catalyzed by lipase has been employed for sugar acylations [40-42]. Other solvents that have been utilized include 2-pyrrolidone [43] for the synthesis of sorbitol ester derivatives. Pyridine and biphasic mixtures of solvents such as benzene/pyridine and tert-hvXy alcohol/hexane have also been used. 

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