Pseudomonas sp. lipase

Further studies of Pseudomonas sp. lipase revealed a strong influence of the water content of the reaction medium (Entry 20) [48]. To be able to compare the enzyme activity and selectivity as a function of the water present in solvents of different polarities, it is necessary to use the water activity (a ) in these solvents. We used the... 

Enzyme-catalyzed stereoselective hydrolysis allows the preparation of enantio-merically enriched lactones. For instance. Pseudomonas sp. lipase (PSL) was found to be a suitable catalyst for the resolution of 5-undecalactone and 5-dodecalactone (Figure 6.20). Relactonization of the hydroxy acid represents an efficient method for the preparation of both enantiomers of a lactone [67]. 

Five-membered unsubstituted lactone, y-butyrolactone (y-BL), is not polymerized by conventional chemical catalysts. However, oligomer formation from y-BL was observed by using PPL or Pseudomonas sp. lipase as catalyst. Enzymatic polymerization of six-membered lactones, 8-VL and l,4-dioxan-2-one, was reported. 8-VL was polymerized by various lipases of different origins. The molecular weight of the enzymatically obtained polymer was relatively low (less than 2000). 

Five-membered unsubstituted lactone, y-butyrolactone, is not polymerized by conventional chemical catalysts. On the other hand, oligomer formation from y-butyrolactone was observed by using PPL or Pseudomonas sp. lipase as catalyst [23,69]. 

Early reports on the effects of the choice of solvent on enzymatic enantioselectivity showed that substantial changes may be observed. For the transesterification reaction of sec-phenethyl alcohol with vinyl butyrate catalyzed by subtilisin Carlsberg, a 20-fold increase in the E-value was reported when the medium was changed from acetonitrile to dioxane [59]. Similar changes were recorded for the prochiral selectivity of Pseudomonas sp. lipase in the hydrolysis of 2-substituted... 

Although lipases from Pseudomonas are usually the catalysts of choice for primary alcohols, 2-(2-furyl)-propan-l-ol (Scheme 4.8 7 n = 0 with instead of S) actually gives a higher E (E = 20) with Candida antarctica lipase (CALB) than it does with Pseudomonas sp. lipase (PSL) (E = 2) on acylation with vinyl acetate in pentane [78]. 

A number of racemic 2-aryloxy-1-propanols 8 have been resolved by Pseudomonas sp. lipase (Amano AK)-catalyzed acylation in diisopropyl ether (DIPE) at 25 °C (Scheme 4.9) [46]. Because an oxygen atom is directly attached to the stereogenic center, the selection rule described in Figure 4.3 does not hold. 

Chiral enantiopure 2,2 -dihydroxybiaryls are important as chiral ligands and are also structural motifs occurring in some natural products. Hydrolase-catalyzed resolution by acylation in organic solvents of some dihydroxybiaryls has been successfully achieved. Thus, the racemic binaphthols 111-113 have been resolved by mono acylation with vinyl acetate in t-butylmethyl ether ( ME) at 45 °C catalyzed by Pseudomonas sp. lipase (Scheme 4.35) [106]. In a similar way the 2,2 -dihydroxybiphenyl 114 can be acylated with vinyl acetate catalyzed by PSL immobilized on celite in TBME at 45 °C (Scheme 4.35) [107]. Butanolysis of the racemic monobutyrate of binaphthol rac-115 catalyzed by CALB in toluene at 80 °C for 72 h gives (R)-binaphthol (93% ) at ca. 50% conversion [108]. 

TIL Thermomyces lanuginosus lipase, RdL Rhizopus delemar lipase, RnL Rhizopus niveus lipase, MmE Mucor miehei esterase, PsL Pseudomonas sp. lipase, MmL Mucor miehei lipase, RoL Rhizopus orvzae lipase, CaLA Candida antarctica lipase A, CaLB Candida antarctica lipase B, PLE Pig liver esterase, EP Enteropeptidase, PKA Porcine kidney acylase, CE Cholesterol esterase Figure 8.1 (S)-Selective enzyme hits from hydrolase screening. ... 

Pseudomonas fragi (enantioselective) Pseudomonas sp. lipase (enantioselective)... 

PPL and lipase from Pseudomonas sp. catalyze enantioselective hydrolysis of sulfinylalkanoates. For example, methyl sulfinylacetate (46) was resolved by Pseudomonas sp. lipase in good yield and excellent selectivity (62). This procedure was suitable for the preparation of sulfinylalkanoates where the ester and sulfoxide groups are separated by one or two methylene units. Compounds with three methylene groups were not substrates for the lipase (65). 

Lipase-catalyzed intermolecular condensation of diacids with diols results in a mixture of macrocyclic lactones and linear oligomers. Interestingly, the reaction temperature has a strong effect on the product distribution. The condensation of a,CO-diacids with a,(0-dialcohols catalyzed by Candida cyiindracea or Pseudomonas sp. lipases leads to macrocyclic lactones at temperatures between 55 and 75°C (91), but at lower temperatures (<45°C) the formation of oligomeric esters predominates. Optically active trimers and pentamers can be produced at room temperature by PPL or Chromobacterium viscosum lipase-catalyzed condensation of bis (2,2,2-trichloroethyl) (+)-3-methyladipate and 1,6-hexanediol (92). 

Table 12.5 Effects of the hydrophobicity (log P) of solvents on the prochiral selectivity (S) of Pseudomonas sp. lipase in the monohydrolysis of 2-(l-naphthoylamino)trimethylene dibutyrate (Terradas, 1993).

At the end of the previous chapter, we discussed the medium dependence of the lipase-catalyzed synthesis of nifedipines, dihydropyridines with an aromatic substituent in the 4-position and often asymmetric ester derivatives in the 3- and 5-positions, which are active as calcium antagonists in cardiovascular therapy. At the Amano Company in Nagoya, Japan, lipase-catalyzed hydrolyses of methylene-oxypropionyl or -pivaloyl diesters with Amano PS (Pseudomonas sp.) lipase were found to yield varying enantiomeric excesses depending on the solvent in cyclohexane the different esters yielded half-esters with 88.8-91.4% e.e. (R)-specificity for a triple mutant ( FVL ) of Amano PS lipase, whereas the same transformation with the same enzyme in diisopropyl ether (DIPE) yielded between 68.1 and > 99% e.e. of the (S)-product (Chapter 12, Figure 12.10) (Hirose, 1992,1995). 

A set of -methylene-/ -hydroxy esters 42 were resolved via enzymatic enantioselective transesterification with Pseudomonas sp. lipase (PCL), free and immobilized one using either vinyl or isopropenyl acetate as acyl donors under different conditions. The corresponding (R)-(+)-acetates (R)-43 and the unreacted (S)-(-)-substrates (S)-42 were obtained with an ee up to >99%.70... 

Enzymatic polymerization of lactones is a promising approach and has been investigated by several workers [45,46,71-78]. Poly(e-CL) with Mn=14,500 and a molecular weight distribution of 1.23 has recently been reported using Pseudomonas sp. lipase as the catalyst [71]. A complex mechanism involving both ring-opening and linear condensation polymerizations has been proposed for the enzymatic polymerization of lactones. 

DKR of aldehydes via cyanohydrins One-pot (iPr)20 Acetone cyanohydrin + anion exchange resin Pseudomonas sp. lipase + 29... 

DKR of alcohol acetylation One-pot C6H12 or CH2C12 and Al, Ir, or Rh catalysts for secondary alcohol Pseudomonas sp. lipase or 21... 

Acyloxygen fission (63 64), e.g., propiolactone reacts with MeOH, H+ to give 64 (Nu = OMe). A Pseudomonas sp. lipase-promoted asymmetric transesterification reaction allows kinetic resolution of racemic 2-oxetanones <2000J(PI)71>. 

In the system described by Williams a rhodium catalyst was used, in the presence of an inorganic base and phenanthroline, and one equivalent of acetophenone, for the racemization, and a Pseudomonas sp. lipase for the acylation using vinyl acetate as the acyl donor (Fig. 9.3). 

Deracemization of mandelic add with the combined action of two enzymes has been reported. rac-MandeUc acid is acylated by a Pseudomonas sp. lipase in diisopropyl ether. After solvent removal the mfacture of mandeUc acid enriched in the R-form and the 0-acetyl derivative of the S-configuration are subjected to the mandelate racemase-catalyzed racemization in aqueous buffer. In these conditions only the non-acetylated hydroxy acid is racemized. In order to obtain (S)-0-acetylmandelic acid in an 80% isolated yield and a >98% e.e. the process must be repeated four times [9]. 

PPL catalyzed the polymerization of methyl esters of 5-hydroxypentanoic and 6-hydroxyhexanoic acids.149 In the polymerization of the latter in hexane at 69 °C for more than 50 days, the polymer with DP up to 100 was formed. Relationships between solvent type and polymerization behaviors were systematically investigated hydrophobic solvents such as hydrocarbons and diisopropyl ether were suitable for the enzymatic production of high molecular weight polymer. Pseudomonas sp. lipase catalyzed the polymerization of ethyl esters of 3- and 4-hydroxybu-tyric acids, 5- and 6-hydroxyhexanoic acids, 5-hy-droxydodecanoic acid, and 15-hydroxypentadecanoic acid.157 Oxyacid vinyl esters were demonstrated as new monomers for polyester production under mild reaction conditions, yielding the corresponding polyesters with A/n of several thousands.276... 

FIGURE 8.2. Transesterification rate of Pseudomonas sp. lipase immobilized by adsorption onto Celite as a function of enzyme loading. (Redrawn from Bovara, R. et al., Biotechnol. Lett., 15, 169-174, 1993. With permission. 

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