Lipase-mediated synthesis

Aleu, J. Brenna, E. Fuganti, C. Serra, S. Lipase-mediated synthesis of the enantiomeric forms of 4,5-epoxy-4,5-dihydro-a-ionone and 5,6-epoxy-5,6-dihydro-/ -ionone. A new direct access to enantiopure (R)- and (S)-a-ionone. 

Welsh, F.W., Williams, R.E., and Dawson, K.H., Lipase mediated synthesis of low molecular weight flavor esters, J. Food Sci., 55, 1679, 1990. 

More recently, Lopez-Luna et al. [54] reported the successful enzyme-mediated syntheses of polyester structures in SCCO2 and R-134a. Lipase-mediated synthesis of relatively high molecular weight poly(S-valerolactone) (PVL) was reported in SCCO2 and liquid R-134a solvent media. However, they found that polymers and copolymers... 

Karuna, M.S.L., Reddy, J.R.C., Rao, B.V.S.K., Prasad, R.B.N., 2005. Lipase-mediated synthesis of alkyl ricinoleates and 12-hydroxy stearates and evaluation of the surfactant properties of their sulfated sodium salts. J. Surfactants Deterg. 8, 271-276. 

Dynamic Kinetic Resolution Synthesis of a Fluorinated Amino Acid Ester Amide by a Continuous Process Lipase-mediated Ethanolysis of an Azalactone... 

T Sugai, H Ohta. Lipase-mediated efficient preparation of both enantiomers of 2-acetoxytetraconsanoic acid, the intermediate for sphingolipid synthesis. Tetrahedron Lett 7063-7064, 1991. 

The full capacity of the lipase-mediated technique for C-terminal deprotection is demonstrated in the synthesis of complex C>-glycopeptides, which are sensitive to both acids and bases, The key starting material, serine glycoside heptyl ester 11, is selectively depro-tected at the C-terminus by lipase obtained from the fungus Mucor javanicus (Scheme 22). The free carboxylic acid derivative 12 is coupled with an N-terminally protected glyco-dipeptide 13 to generate the tripeptide 14. 

The whole capacity of the lipase-mediated deprotection techniques described above was demonstrated in the synthesis of complex and sensitive glycopeptides carrying the characteristic linkage region present in biologically important 0-glycoproteins [48, 54]. Thus, the serine glycoside heptyl ester 43 was selec-... 

Immobilized enzymes are currently the object of considerable interest. This is due to the expected benefits over soluble enzymes or alternative technologies. The number of applications of immobilized enzymes is increasing steadily [5]. Occasionally, however, experimental investigations have produced unexpected results such as a significant reduction or even an increase in activity compared with soluble enzymes. Thus, cross-linked crystals of subtihsin showed 27 times less activity in the aqueous hydrolysis of an amino acid ester compared to equal amounts of soluble enzyme [6]. On the other hand, in the application of hpo-protein lipase in the solvent-mediated synthesis of esters there was a 40-fold increase in activity using immobihzed or otherwise modified enzyme preparations as compared to enzyme powder [7]. 

The first chemoenzymatic synthesis of organoselenium containing amines was recently reported by Andrade and Silva (Figure 14.7) [10]. Compounds containing a selenium atom have important antioxidant and anti inflammatory activities. Lipase mediated acylation of amine 13 gave the corresponding chiral amides 14 and amines 13 with excellent enantioselectivity (up to 99% ee). 

Bjorkling, R, Frykman, H., Godtfredsen, S. E., and Kirk, O., Lipase catalyzed synthesis of peroxycarboxyhc acids and lipase mediated oxidations. Tetrahedron, 48, 4587-4592, 1992. 

Esterification. The lipase-mediated esterification is promoted by microwave (90°, 15 min.). Four lipases immobilized in microemulsion-based gels retain their activity in catalyzing esterification. Resolution by selective acetylation of ethyl 6-hydroxy-1-cyclohexenecarboxylate gives access to a chiral intermediate for a synthesis of the spirocyclic alkaloids (+)-nitramine, (+)-isonitramine, and (-)-sibirine. 

Finally, the use of stoichiometric amounts of transition metal complexes can play an important role in the synthesis of functionalized piperidines. <01H14.39> Liebeskind and coworkers have developed a chiral transition metal complex and have used it in the synthesis of (-)-indolizidine 209B <01JA12477>. A lipase mediated allylic alcohol resolution provides access to both antipodes of enantiomerically pure allyl acetates (115) which can be used to form an ri -allyl molybdenum complex (116), Hydride abstraction followed by methoxide quench yields a reactive species 117 which may be further functionalized through reactions with Grignard reagents. The eventual products 119 arc 2,3,6-trisubstituted piperidines in enantiomerically pure form. 

Lipase-catalyzed polyester synthesis has received considerable interest [31] due to the harsh conditions used in traditional chemical polymerization (> 200 C), and has also been subjected to reaction in ILs. Both CaLB and PcL lipases have been found to catalyze polyester synthesis in [BMIM][BF4] and [BMIM][PF6], but this approach does not seem to offer any advantages over state-of-the-art lipase-mediated polyester synthesis [32, 33] [Eq. (3)]. Still, the polydispersity index of the polymers formed in ILs were remarkably affected, giving values close to 1, which indicate a very narrow molecular weight range compared to material prepared by conventional polymerization processes [33]. 

Frykman, H. B. and T.A. Isbell, Synthesis of 6-Hydroxy 8-Lactones and 5,6-Dihydroxy Eicosanoic/Docosanoic Acids from Meadowfoam Fatty Acids via Lipase-Mediated Self-Epoxidation, J. Am. Oil Chem. Soc. 74 719-722 (1997). 

Bjorkliiig, F., H. Fiykman, S.E. Godtfredsen, and O. Kirk, Lipase Catalyzed Synthesis of Peroxycarboxylic Acids and Lipase Mediated Oxidations, Tetrahedron 48 4587-4592 (1992). 

High yields and >99% ee were achieved in the lipase-mediated desymmetrization of 2,3-0-cyclohexylidene-erythritol 34, as shown in Scheme 3. The acetonide 35 was similarly asymmetrically acetylated to give the monoacetate 36, which was employed in a synthesis of (+)-em/o-brevicomin (see Chapter 24). The enzymatic kinetic resolution of racemic synthetic glycals is referred to in Chapter 13. 

Excellent yields were achieved in the selective acylation at 0-3 of 6-0-acelyl-l,5-anhydro-2-deoxy-D-arafe/no-hex-l-enitol (25) by lipase mediated acyltransfer from several vinylesters. As shown in Scheme 7, the starting material (25) could be recovered in 80% yield from two of the products (26) by enzymatic hydrolysis. Reports have been published on the lipase mediated selective synthesis of 2-functionalised 3-monoesters (27) of methyl 5-0-decyl-a-D-arabinofuranoside, on the regioselective, lipase-catalysed acylation of methyl a- and -D-arabino- and -xylo-pyranoside, on the regioselective acylation and deacylation of 2 -deoxynucleoside derivatives by use of a Pseudomonas fluorescens lipase and a Bacillus subtilis protease, respectively, and on the regioselective acylation of castanospermin with a variety of enzymes in pyridine. 

Hydrolases, especialy lipases, are noted for their tolerance of organic solvents, and are obvious candidates for the enzymatic synthesis in ILs (Sureshkumar Lee, 2009). Indeed, lipases from Candida antarctica, Burkholderia cepacia (formerly Pseudomonas cepacia), and Alcaligenes sp. are catalytically active in ILs (Itoh et al, 2001 Nara et al., 2002). Additionally, lipases mediate transesterification reactions in these ILs with an efficiency comparable to that in tert-butyl alcohol, dioxane, or toluene (Lau et al., 2000 Nara et al., 2002 Park Kazlauskas, 2001). 

Tetroses and Pentoses. - The application of the Strecker synthesis to the preparation of 2-amino-2-deoxytetrose derivatives is covered in Chapter 9 and a lipase-mediated route to 4-carbon diols and triols is referred to in Chapter 18. 

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