Chromobacterium lipase

Lipase-catalyzed intermolecular condensation of diacids with diols results in a mixture of macrocycUc lactones and liuear oligomers. Interestingly, the reaction temperature has a strong effect on the product distribution. The condensation of a,(D-diacids with a,(D-dialcohols catalyzed by Candida glindracea or Pseudomonas sp. Upases leads to macrocycUc lactones at temperatures between 55 and 75°C (91), but at lower temperatures (<45°C) the formation of oligomeric esters predorninates. Optically active trimers and pentamers can be produced at room temperature by PPL or Chromobacterium viscosum Upase-catalyzed condensation of bis (2,2,2-trichloroethyl) (+)-3-meth5ladipate and 1,6-hexanediol (92). 

Chromobacterium viscosum lipase, cyclohexane, vinyl acetate, THF, 40°." Cleavage... 

Under comparable conditions, the reaction rates of the octyl decanoate synthesis by chromobacterium viscosum lipase in AOT-based microemulsions or immobihzed in AOT-based organogels were similar [286,287],... 

In turn, a lipase-promoted acylahon of prochiral substrates 104, using lipases from Candida cylinracea and Chromobacterium viscosum and methyl isobutyrate or acetoxime isobutyrate as the acyl donors, gave the product 105 in yields up to 80% and with ees up to 75% (Equahon 50). ... 

Isolation of lipase A from lipase B from crude Chromobacterium viscosum extract [80,81]... 

Lipase from Chromobacterium viscosum Esterification of 1-butanol and oleic acid Oil-deionized water (96.6/3.4) 14.2 103... 

Lipase from Chromobacterium viscosum Transesterification of 2-ethyl-l-hexanol and rapeseed oil Oil-water (97/3) 97.2 103... 

A Chromobacterium viscosum lipase is microencapsulated in AOT reversed micelles in isooctane with a Wo=24 and used in the controlled hydrolysis of 50 mM triolein at pH 7.0 and 35°C, in a continous stirred membrane reactor, with a flow rate of 1 l.min 1 Design the reactor in order to achieve 95% of conversion. 

Kinetic optical resolution of racemic alcohols and carboxylic acids by enzymatic acyl transfer reactions has received enormous attention in recent years56. The enzymes generally employed are commercially available lipases and esterases, preferentially porcine liver esterase (PLE) or porcine pancreatic lipase (PPL). Lipases from microorganisms, such as Candida cylindracea, Rhizopus arrhizus or Chromobacterium viscosum, are also fairly common. A list of suitable enzymes is found in reference 57. Standard procedures are described in reference 58. Some examples of the resolution of racemic alcohols are given39. 

However, it seems that empirical trials are still necessary in order to achieve a successful synthesis several enzymes from different natural sources should be tested, and even enzymes having different specificities. For laboratory-scale preparations, the cost of such enzymes as the lipases from porcine pancreas (PPL), Candida cylindracea (CCL), and Chromobacterium viscosum (CVL), and Protease N (Amano) is negligible. Subtilisin, a protease, is much more expensive. 

A number of steroids have been regioselectively acylated in a similar manner (99,104). Chromobacterium viscosum lipase esterifies 5a-androstane-3p,17p-diol [571-20-0] (75) with 2,2,2-trifluoroethyl butyrate in acetone with high selectivity. The lipase acylates exclusively the hydroxy group in the 3-position giving the 3p-(monobutyryl ester) of (75) in 83% yield. In contrast, bacillus subtilis protease (subtilisin) displays a marked preference for the C-17 hydroxyl. Candida cylindracea lipase (CCL) suspended in anhydrous benzene regioselectively acylates the 3a-hydroxyl group of several bile acid derivatives (104). 

Enantioselective enzymatic transesterifications have been successfully used for the synthesis of optically active silanes with the silicon atom as the center of chirality. As shown in Scheme 20, the prochiral bis(hydroxymethyl)silanes 86 and 88 were transformed into the corresponding chiral dextrorotatory isobutyrates (+)-87 and (+)-89, respectively, using Candida cylindracea lipase (CCL, E.C. 3.1.1.3) as the biocatalyst73. For these bioconversions, methyl isobutyrate was used as solvent and acylation agent. When using acetoxime isobutyrate as the acylation agent and Chromobacterium viscosum lipase (CVL ... 

The 5 -(-)-2-cyclohexy 1-1,3-propanediol monoacetate (24) and the S-( )-2-phenyl-1,3-propanediol monoacetate (25) are key chiral intermediates for the chemoenzymatic synthesis of Monopril (26) (Fig. 10), a new antihypertensive drug which acts as an ACE inhibitor. The asymmetric hydrolysis of 2-cyclohexyl-1,3-propanediol diacetate (27) and 2-phenyl-1,3-propanediol diacetate (28) to the corresponding S-( - )-monoacetate (24) and S-( )-monoacetate (25) by porcine pancreatic lipase (PPL) and Chromobacterium viscosum lipase have been demon-... 

Another example using a prochiral acetate and asymmetric hydrolysis was described by the Bristol-Myers Squibb group for an intermediate in the synthesis of Monopril (fosinopril sodium) (41), an ACE inhibitor (Scheme 19.23). The prochiral substrate 42 was hydrolyzed both when R = phenyl or cyclohexyl to the corresponding (S)-(-)-monoacetate 43. The reaction was carried out in a 10% toluene biphasic system with either PPL or Chromobacterium viscosum lipase. The cyclohexyl monoacetate was obtained in 90% yield with an optical purity of 99.8%.107 195... 

A lipase from Arthrobacter species yielded pure (R)-HMPC at 50% hydrolysis with the smallest amount of the enzyme. Lipases from Pseudomonas fluorescens, Chromobacterium viscosum and Alcaligenes species were of less interest to us than the Arthrobacter lipase among others, judging from the optical purity of the product, degree... 

There are also several reports on highly regioselective transesterification of various steroid derivatives, one example being displayed in eq 14 in which butyration occurred exclusively at the 3p-hydroxyl group by Chromobacterium viscosum lipase (CVL). Opposite regioselectivity toward the 17p-hydroxyl group was observed with subtilisin protease. ... 

Microbial lipases from Aspergillus niger (AN), Candida cylindracea (CC), Pseudomonas spp. (PS), Chromobacterium viscosum (CV), Rhizopus delemer (RD), and Rhizopus javanicus (RJ) have been widely used in modifying PUFA-rich oils (117). The fatty acid specificity of lipases (discrimination of PUFA over short-chain fatty acids) is a crucial factor when considering the application of enzymes to modify marine oils rich in PUFA (118-121). Lipases from Rhizopus spp are known to be 1,3-position specific (122). Wanasundara (79) and Wanasundara and Shahidi (123, 124) (seal blubber oil SBO and menhaden oil MHO) and Tanaka et al. (117)... 

Lang, D., Haalck, L., Hofmann, B., Hecht, H.-J., Spener, F., Schmid, R. D. and Schomburg, D. (1994) Crystallization and preliminary X-ray analysis of a lipase from Chromobacterium viscosum. Acta Cryst. 50, 225-227... 

PCL was also degraded to 6-hydroxyhexanoic acid during enzymatic hydrolysis by Lipase Asahi derived from Chromobacterium viscosum and Hp-ase F derived from Rhizopus niveus [74]. In another study formation of oligomers during biotic hydrolysis of PCL was shown by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) [50]. Enzymatic degradation of copolymers of 3-hydroxybutyric acid (3HB) and... 

Table 11.1-11. Lipase-catalyzed enantiotopos-differentiating hydrolysis of prochiral cyclic diol dialkanoates in aqueous solution (CCL Candida cylindracea lipase, PFL Pseudomonas jiuorescens lipase, MML Mucor miehei lipase, CVL Chromobacterium viscosum lipase, PPL pig pancreas lipase, MJL Mucor javanicus lipase, RSL Rhizopus sp. lipase, PCL Pseudomonas cepacia lipase, CCL, Ceotricum candidum lipase, ANL Aspergillus niger lipase, FSPC Fusarium solani pisi cutinase, CRL Candida rugosa lipase, CAL-B Candida antarctica B lipase, LIP Pseudomonas sp. lipase-Toyobo, RDL Rhizopus delemar lipase, MSL Mucor sp. lipase, CAL Candida antarctica lipase, not specified).

Table 11.1-12. Lipase-catalyzed enantiotopos-differentiating hydrolysis of prochiral acyclic and cyclic dicarboxylic acid diesters in aqueous solution (CCL Candida cylindracea lipase, PPL pig pancreas lipase, PSL Pseudomonas sp. lipase, CVL Chromobacterium viscosum lipase,...

R = n-butyryl lipase from Chromobacterium viscosum (CVL), Pseudomonas sp. or Mucormiehei (MML) 91%... 

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