Lipase synthesis

Ester synthesis of cholesterol linoleate. Cholesterol fatty acid ester is an important cell membrane lipids and has many applications in cosmetics, pharmaceutical and other industries. Akehoshi et aL(7) reported the ester synthesis of the cholesterol fatty acid ester with native lipase. Synthesis of the cholesterol fatty acid ester was also carried out in water-saturated n-hexane by palmitic acid-modified lipase. As shown in Table III, this system made it possible for the synthesis of the cholesterol fatty acid ester in organic solvents using the modified lipase. 

Lipoprotein lipase, like many enzymes, has several isozymic forms that differ from one tissue to the next. Insulin is known to enhance lipoprotein lipase synthesis in the capillary endotheliiun next to adipocytes, whereas it has no such effect in the myocardium. Why might this have come about ... 

Defective pancreozymin stimulation Decreased lipase synthesis... 

Iriuchijima, S. and Kojima, N. (1982) Asymmetric hydrolysis of (+)-l,2-diacetoxy-3-chloropropane and its related compounds with lipase. Synthesis of optically pure (5)-propranolol. Agric. Biol Chem. 46, 1153-1157. 

A. Cuetos, M.L. Valenzuela, L. Lavandera, G.A. Carriedo, Polyphosphazenes as tunable and recyclable supports to immobilize alcohol dehydrogenases and lipases synthesis, catalytic activity, and recycling efficiency, Biomacromolcules 11 (2010) 1291-1297. 

The ability of lipases to synthesize the amide bond has been shown (26). Mucor miehei lipase (NOVO tipozyme) has been used in the reaction of laurylamine and oleic acid at 60°C. Water was shown to inhibit the synthesis of this Ai-lauryloleamide (27). 

Both saturated (50) and unsaturated derivatives (51) are easily accepted by lipases and esterases. Lipase P from Amano resolves azide (52) or naphthyl (53) derivatives with good yields and excellent selectivity. PPL-catalyzed resolution of glycidyl esters (54) is of great synthetic utiUty because it provides an alternative to the Sharpless epoxidation route for the synthesis of P-blockers. The optical purity of glycidyl esters strongly depends on the stmcture of the acyl moiety the hydrolysis of propyl and butyl derivatives of epoxy alcohols results ia esters with ee > 95% (30). 

Lipase-catalyzed enantioselective transesterification of 0-substituted-l,2-diols is another practical route for the synthesis of P-blockers. Lipase PS suspended in toluene catalyzes the transesterification of (63) with vinyl acetate to give the (5)-ester in 43% yield and >98% ee (78). The desired product, optically pure (R)-ttitylglycidol, is then easily obtained by treating the ester with alcohoHc alkaU. Moreover, Pseudomonas Hpase catalyzes the acylation of oxazohdinone (64) with acetic anhydride in very good yield and selectivity (74). PPL-catalyzed transesterification of a number of /n j -norbomene derivatives proceeds in about 30% yield and 92% ee (79,80). 

FIGURE 25.17 Hormonal signals regulate fatty acid synthesis, primarily through actions on acetyl-CoA carboxylase. Availability of fatty acids also depends upon hormonal activation of triacylglycerol lipase. 

A benzyl carbonate was prepared in 83% yield from the sodium alkoxide of glycerol and benzyl chloroformate (20°, 24 h). It was also prepared by a lipase-catalyzed ester exchange with allyl benzyl carbonate. It is cleaved by hydrogenolysis (H2/Pd-C, EtOH, 20°, 2 h, 2 atm, 76% yield) and electrolytic reduction (—2.7 V, R4N X, DMF, 70% yield). A benzyl carbonate was used to protect the hydroxyl group in lactic acid during a peptide synthesis." ... 

The advantages of the methoxyethyl ester over some of the other water-solubilizing esters are that many of the amino acid esters are crystalline and thus easily purified, are cleaved with a number of readily available lipases, and are useful for the synthesis of A-linked glycopeptides. ... 

Increased lipid synthesis/inhibi-tion of lipolysis Activation of lipoprotein lipase (LPL)/induc-tion of fatty acid synthase (FAS)/inactivation of hormone sensitive lipase (HSL) Facilitated uptake of fatty acids by LPL-dependent hydrolysis of triacylglycerol from circulating lipoproteins. Increased lipid synthesis through Akt-mediated FAS-expression. Inhibition of lipolysis by preventing cAMP-dependent activation of HSL (insulin-dependent activation of phosphodiesterases )... 

A very attractive and efficient method for the synthesis of L-aminoacids via DKR has been reported by Turner et al. [41a,b]. They employed enzyme-catalyzed ring opening of 5(4H)-oxazolones in combination with a catalytic amount of Et3N. The relatively low pKa of the C-4 proton (8.9) of oxazolones facilitates racemization. Hydrolysis of the ester obtained through DKR, followed by debenzoylation, yields L-aminoacids in excellent enantiomeric excess (99.5%) (Figure 4.16). In their initial studies, they employed Rhizomucor miehei lipase (Lipozyme) as the biocatalyst [41]. More recently, they have obtained excellent results employing CALB [41bj. This method has also been employed by Bevinakatti [41c,d] and Sih [41e,fj. 

In 1992, Oda et al. reported a one-pot synthesis of optically active cyanohydrin acetates from aldehydes, which were converted to the corresponding racemic cyanohydrins through transhydrocyanation with acetone cyanohydrin, catalyzed by a a strongly basic anion-exchange resin [46]. The racemic cyanohydrins were acetylated by a lipase from P. cepacia (Amano) with isopropenyl acetate as the acyl donor. The reversible nature of the base-catalyzed transhydrocyanation enabled continuous racemization of the unreacted cyanohydrins, thereby effecting a total conversion (Figure 4.21). 

The first asymmetric synthesis of (—)-Y-jasmolactone, a fruit fiavor constituent, vas achieved via the enantioselective lactonization (desymmetrization) of a prochiral hydroxy diester promoted by porcine pancreas lipase (PPL) (Figure 6.23) [71]. 

The principal methods for the hydrolase-promoted synthesis of enantiomerically pure alcohols are depicted in Figure 6.44. Biocatalytic acylation and alcoholysis have been reviewed recently [116,117]. Lipases, esterases, and proteases catalyze these reactions, but CAL-B [118-120], CRL [121,122], and diverse lipase preparations from Pseudomonas species are common place. 

Combination of lipase-catalyzed transesterification with unsaturated vinyl esters as acyl donors and ring-closing metatheses (RCMs) have also been reported [146-148]. Two groups applied this strategy for the synthesis of goniothalamin from cinnamaldehyde [147,148]. The key steps were a transesterification using vinyl acrylate as acyl donor, followed by an RCM, as depicted in Figure 6.55. 

---