Regioisomerically pure 1(3)-rac-monoacylglycerols are conveniently prepared in high yields (>75%) and in multigram quantities by enzymatic esterification of glycerol in the presence of various lipases(Chromobacterium viscosum, Rhizopus delemar, Rhizomucor miehei) with a variety of different acyl donors, such as free fatty acids, fatty acid alkyl esters, vinyl esters and triacylglycerols, as well as natural fats and oils. All reactions are carried out in aprotic organic solvents with low water content, namelyn-hexane, diethyl ether, tBuOMe or mixtures of these solvents. Essential for the success of these transformations were the following two factors. First, the creation of an artificial interphase between the solvent-immiscible hydrophilic glycerol and the hydrophobic reaction medium by its adsorption onto a solid support. Second, a facile system for the separation of the desired monoacylglycerol from the reaction mixture, coupled with the continuous recycling of acyl donor and undesirable by-products.

Enzymatic esterification of glycerol II. Lipase-catalyzed synthesis of regioisomerically pure 1(3)-rac-monoacylglycerols

http://www.farm.ucl.ac.be/Full-texts-FARM/Lambert-2000-1.pdf

Rationale and applications of lipids as prodrug carriers.

1,3-Diacylglycerols were synthesized by direct esterification of glycerol with free fatty acids in a solvent-free system. Free fatty acids with relatively low melting points (<45°C) such as unsaturated and medium-chain saturated fatty acids were used. With stoichiometric ratios of the reactants and water removal by evaporation at 3 mm Hg vacuum applied at 1 h and thereafter, the maximal 1,3-diacylglycerol content in the reaction mixture was: 84.6% for 1,3-dicaprylin, 84.4% for 1,3-dicaprin, 74.3% for 1,3-dilinolein, 71.7% for 1,3-dieicosapentaenoin, 67.4% for 1,3-dilaurin, and 61.1% for 1,3-diolein. Some of the system’s parameters (temperature, water removal, and molar ratio of the reactants) were optimized for the production of 1,3-dicaprylin, and the maximal yield reached 98%. The product was used for the chemical synthesis of 1,3-dicapryloyl-2-eicosapentaenoylglycerol. The yield after purification was 42%, and the purity of the triacylglycerol was 98% (both 1,3-dicapryloyl-2-eicosapentaenoylglycerol and 1,2-dicapryloyl-3-eicosapentaenoylglycerol included) by gas chromatographic analysis, of which 90% was the desired structured triacylglycerol (1,3-dicapryloyl-2-eicosapentaenoylglycerol) as determined by silver ion high-performance liquid chromatographic analysis.

Enzymatic synthesis of symmetrical 1,3-diacylglycerols by direct esterification of glycerol in solvent-free system

Swelling of charged bilayers can extend to well over 100 nm without loosing long range order. Attraction induced by solutes or screening induced by salt or buffers reduce the maximum periodicity. Microstructural evolutions near the maximum swelling are reviewed as well as associated equations of state, i.e. osmotic pressures versus interlayer distances. We describe the different mechanisms which have been identified as limiting the swelling of a lamellar phase, and the phase equilibria involved when maximum swelling limit is reached.

Swelling limits for bilayer microstructures: the implosion of lamellar structure versus disordered lamellae

Lipases that display high regioselectivities and broad substrate tolerance were used as catalysts for the efficient esterification of glycerol under the conditions of irreversible acyl transfer. A variety of unsaturated fatty acids, such as oleic, linoleic, erucic, ricinolic, hydroxystearic and coriolic acid, were used for this purpose in the form of their vinyl esters. Suitable biocatalysts were chosen on the basis of systematic screening experiments regarding their regioselectivities (RE) and substrate tolerances. Distinct differences were found and expressed in numerical RE values as a measure for differences of these biocatalysts as being specific, selective, and nonspecific. Based on these experiments, a variety of molecules were synthesized on a preparative scale (>150 mmol) in good yield (ca.85%) and with high regioisomerical purities (>95% RE).

Enzymatic esterification of glycerol III. Lipase-catalyzed synthesis of regioisomerically pure 1,3-sn-diacylglycerols and 1 (3)-rac-monoacylglycerols derived from unsaturated fatty acids

P. Speiser

Papers

Phase behaviour of a diglyceride prodrug: spontaneous formation of unilamellar vesicles.