Lipases in organic solvents

Using this approach, racemates of (27) were enantiomerically enriched using a lipase in organic solvent, followed by racemization of the unreacted enantiomer in buffer. Acylated derivatives (S)-(28) were obtained in yields >50% and >99% ee. Lipases with the opposite enantioselectivity produced (R)-28 in >99% ee. Subsequent chemical deacylation of (28) yielded enantiomerically enriched (27). 

In particular, the combined action of a transition metal catalyst and a lipase in organic solvents for the racemization and esterification steps, respectively, has been applied for the conversion of racemic secondary alcohols into their esters... 

K. Naemura, K. Kittaka, M. Murata, H. Ida, K. Hirose, Y. Tobe, Lipase-Catalyzed Enantioselective Alcoholysis of Enol Acetates Optical Resolution of Ketones and Aldehydes Using Lipases in Organic Solvents , Enantiomer 1996, 1, 219-222. 

K. Yamamoto, T. Nishioka, J. Oda, Y. Yamamoto, Asymmetric Ring Opening of Cyclic Acid Anhydrides with Lipase in Organic Solvents , Tetrahedron Lett. 1988, 29, 1717-1720. 

By screening a variety of lipases in organic solvent for their ability to acylate the racemic hydroxynitrile with succinic anhydride, Novozym 435 was found to yield the best results, affording product in 94-95 % ee at conversions of 47 9 % (Scheme 1.34). After optimization, the reaction was successfully run at 22 kg scale. The immobilized catalyst could be easily isolated by filtration and reused. 

Secundo, E., Riva, S. and Carrea, G., Effects of medium and of reaction conditions on the enantioselectivity of lipases in organic solvents and possible rationales. Tetrahedron Asymm. 1992, 3, 267-280. 

It is worth noting that the enzyme can be withdrawn and recycled by using supercritical CO2. The success of the polymerizations carried out in organic solvents stems directly from the sustained activity of several lipases in organic solvents. In this respect, it must be noted that water has a manifold influence on the course of the polymerization. On the one hand, water can initiate the polymerization. On the other hand, a minimum amount of water has to be bound to the surface of the enzyme to maintain its conformational flexibility, which is essential for its catalytic activity [94]. Lipase-mediated polymerization cannot therefore be achieved in strictly anhydrous conditions. 

Surfactants have been used to solubilise lipases in organic solvents (Okahata and Mori, 1997). One method starts with mixing aqueous solutions of the surfactant and the enzyme. The enzyme-surfactant complex precipitates and can subsequently be dissolved in organic media. Several surfactants have been tested and especially good results have been obtained with dialkyl glucosyl glutamates. In one case it was shown that the complex consisted of one enzyme molecule surrounded by approximately 150 surfactant molecules. 

Lara, P. V., and Park, E. Y. 2004. Potential application of waste activated bleaching earth on the production of fatty acid alkyl esters using Candida cylindracea lipase in organic solvent system. Enzyme and Microb. Technol., 34, 270-277. 

Inagaki M, Hiratake J, Nishioka T, Oda J (1989) Kinetic resolution of racemic benzaldehyde cyanohydrin via stereoselective acetylation catalyzed by lipase in organic solvent. Bull Inst Chem Res, Kyoto Univ 67 132-135... 

A search for analogues of Castanospermine as inhibitors for human immunodeficiency virus (HIV)627 illustrates the use of lipases in organic solvents pioneered in Klibanov s laboratory.62 Castanospermine [333.1, Scheme 4.333J underwent selective esterification of the Cl hydroxyl function using subtilisin in pyridine. A second selective acylation of the C7 hydroxyl in 333.2 was accomplished with the lipase isolated from Chromohacterium viscosum (CV) to give the 1,7-di-w-butanoyl derivative 333J from which the Cl acyl function was selectively removed using subtilisin in aqueous media. 

Importance of Enzyme Formulation for the Activity and Enantioselectivity of Lipases in Organic Solvents... 

Why do Additives Affect the Activity and Enantioseiectivity of Lipases in Organic Solvent ... 

Kwon, D.Y., Hong, Y.J., and Yoon, S.H., Enantiomeric synthesis of (S)-2-methylbutanoic acid methyl ester, apple flavor, using lipases in organic solvent, J. Agric. Food Chem., 48, 524, 2000. 

Bovara, R., Carrea, G., Ottolina, G., and Riva, S., Water activity does not influence the enantioselectivity of lipase and lipoprotein lipase in organic solvents, Biotechnol. Lett., 15, 169-174, 1993. 

Thus, the coumarine 180, the chromanone 181, the chalcone 182, the flavanone 183 as well as several flavones, e. g. 183 and 185 were regioselectively deacylated by employing different lipases in organic solvents (Fig. 18-24). Porcine pancreatic lipase (PPL) predominantly attacks one of the phenolic acetates present in 180-183 with... 

Li, Z.Y, and Ward, O.P. 1994. Synthesis of monoglyceride containing omega-3 fatty acids by microbial lipase in organic solvent. J. Ind. Microbiol. 13 49-52. 

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... 

Buisson P, Pierre AC (2006) Immobilization in quartz fiber felt reinforced silica aerogel improves the activity of Candida rugosa lipase in organic solvents. J Mol Catal B Enzym 39 77-82... 

Herbst D, Peper S, Fernandez JF, Ruck W, Niemeyer B. Pressure effects on activity and selectivity of Candida rugosa lipase in organic solvents.J Mol Catal B Enzym 2014 100 104-10. 

Mine, Y., Fukunaga, K., Itoh, K., Yoshimoto, M., Nakao, K., and Sugjmura, Y., Enhanced enzyme activity and enantioselectivity of lipases in organic solvents by crown ethers and cyclodextrins, f. Biosci. Bioeng., 95(5) 441-447, 2003. 

A number of selective acylations and deacylations catalysed by enzymes, especially by lipases in organic solvents, have been reported. Methyl pentofuranosides could be selectively acetylated at 0-5 on a preparative scale by use of a lipase and 2,2,2-trifluoroethyl acetate as acyl donor in THF, while selective hydrolysis could be effected at the primary positions of peracetylated methyl pentofuranosides and hexopyranosides, and at the anomeric centres of peracetylated D-rilao- and D-xylo-furanoses and -pyranoses with lipases in aqueous DMF. ° Methyl -D-glucopyranoside, D-mannose, and 2-acetamido-2-deoxy-D-mannose were all substituted selectively at 0-6 by lipase-mediated... 

Millqvist-Fureby, A. Gao, C. Vulfson, E.N. Enzymatic synthesis of ethoxylat-ed glycoside esters using glycosidases in supersaturated solutions and lipases in organic solvents. Biotech. Bioeng. 1998, 59, 747-753. 

The secondary butanoylation of 6-0-butanoyl esters (17) and (18) and thdr enantimners by a number of lipases in organic solvents has been investigated in some detail. Good yields of the 2,6- and 2,4-diester, respectively, were obtained from the D-galactoside and from the L-mannoside. ... 

Berger, M and Schneider, MP (1991) Lipases in organic solvents the fatty acid chain length profile. Biotechnol. Lett., 13, 641-645. 

B.C. Koops, H.M. Verheij, A.J. Slotboom, M.R. Egmond, Effect of chemical modification on the activity of lipases in organic solvents. Enzyme Microb. Tech., 25 (7) 622-631,1999. 

Gardossi L, Bianchi D KUbanov AM. 1991. Selective acylation of peptides catalyzed by lipases in organic solvents. Journal of the American Chemical Society 113(16) 6328-6329. 

Watanabe Y, Nagai M, Yamanaka K, Jose K, Nomura M. 2009. Synthesis of lauroyl phenoUc glycosides by immobiLized lipase in organic solvent and its antioxidative activity. Biochem Eng J 43 261-265. 

Maugard, T., Remaud-Simeon, M. and Monsan, P. (1998) Kinetic study of chemoselective acylation of amino-alditol by immobilized lipase in organic solvent effect of substrate ionization. 

Lipase-catalyzed kinetic resolution of a-methylbenzylamine using lipases in organic solvents. 

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