Lipase CaLB

Very recently the Meerwein-Ponndorf-Verley-Oppenauer (MPVO) reaction has been exploited for the racemization of alcohols using inexpensive aluminum-based catalysts. Combination of these complexes with a lipase (CALB) results in an efficient DKR of sec-alcohols at ambient temperature. To increase the reactivity of the aluminum complexes, a bidentate ligand, such as binol, is required. Also, specific acyl donors need to be used for each substrate [31] (Eigure 4.9). 

A combination of an enzymatic kinetic resolution and an intramolecular Diels-Alder has recently been described by Kita and coworkers [23]. In the first step of this domino process, the racemic alcohols ( )-8-55 are esterified in the presence of a Candida antarctica lipase (CALB) by using the functionalized alkenyl ester 8-56 to give (R)-8-57, which in the subsequent Diels-Alder reaction led to 8-58 in high enantioselectivity of 95 and 91 % ee, respectively and 81 % yield (Scheme 8.15). In-... 

In a similar investigation, transesterification reactions of vinyl acetate with alcohols in [BMIM]BF4 and [BMIM]PF6 in the presence of immobilized lipases CALB and PS-C were found to proceed with higher enantioselectivities than in THF or toluene, with the best result again being observed with [BMIM]PF6 (280). 

As shown in Figure 6.5, two lipases-CalB and PS-showed a remarkable complementary selectivity toward the hydroxyl groups of different 2 -deoxynucleosides. Specifically, CalB acylated the expected C-5 OH, whereas lipase PS directed its action toward the secondary C-3 OH. In this way, several monoesters were prepared in high yields [77]. Moreover, the same selectivity was... 

Figure 6.8 Regioselective deacylation of the polyacetilated flavonoid quercetin (28a) by action of different lipases (CalB, lipase from Candida antarctica Mml, lipase from Mucor miehei f-BME, ferf-butyl methyl ether)...

The single most used lipase for biocatalysis is probably the Candida antarctica B-lipase (CALB) [42]. It is commercialized by Novozymes in liquid formulation as well as in immobilized form under the trade name Novozym 435 (previously SP 435). CALB has high activity on a wide range of substrates (it has some problems with very bulky substrates), often with outstanding selectivities. Formulated as Novozym 435 it is stable up to approx. 90 °C in solvents such as toluene (or solvent-free reaction mixtures). The A-lipase (CALA), currently only commercially available in liquid form, has attractive properties too, including even better thermostability and higher activity on sterically hindered substrates [43]. 

Enantiomerically pure functional polycarbonate, having many potential biomedical uses, was synthesised from a novel seven-membered cyclic carbonate monomer derived from naturally occurring L-tartaric acid, using four commercially available lipases from different sources at 80 ° C, in bulk. The highest number-average MW, Mn = 15,500 g/mol, polydispersity index (PDI) = 1.7, [a]o ° = +77.8 and melting temperature (Tm) = 58.8 °C, optically active polycarbonate was obtained with lipase CALB [61]. 

In the same year, Trauthwein et al. reported the synthesis of an easy-to-handle and stable racemisation catalyst for secondary alcohols by an in situ mixture of readily available [Ru(p-cymene)Cl2]2 with chelating aliphatic amines. The optimisation of the reaction revealed that N,N,N, N -tetr3. methyl-l,3-propanediamine as the ligand racemised aromatic alcohols completely within 5 h. The combination of this catalyst with lipase CALB showed a good performance for the DKR of various alcohols in the presence of p-chlorophenyl acetate as the acyl donor, as shown in Scheme 8.20. 

The lipase-ruthenium-catalysed DKR of other functionalised alcohols, such as diols, has been widely studied by Backvall et al. in recent years. These authors have developed a highly efficient synthesis of enantiopure diacetates of the symmetric diols, 2,4-pentanediol and 2,5-hexanediol, by combining Backvall s catalyst with lipase CALB, in the presence of vinyl acetate or isoproprenyl acetate as the acyl donor, respectively. Excellent yields, and diastereo- and enantioselectivities were obtained in both cases. 

In 2012, Ikariya et al. found that a combined catalyst system of bifunctional amidoiridium complexes derived from benzylic amines with lipase CALB could provide a range of chiral acetates from racemic secondary alcohols through DKR with nearly perfect enantioselectivities, as shown in Scheme 8.65. ° ... 

In another area, the asymmetric reductive acylation of ketoxime of m-methoxyacetophenone was developed by Kim and co-workers, in 2010. This process was catalysed by a combination of lipase CALB with a palladium nanocatalyst in the presence of ethyl methoig acetate as an acyl donor, molecular sieves in toluene at 70 °C under 0.1 bar of hydrogen pressure. It allowed the formation of the corresponding almost enantiopure amide in high yields of up to 91% and with enantioselectivity of 98% ee, as shown in Scheme 8.77. The utility of this novel methodology was applied to the total synthesis of the calcimimetic (-l-)-NPS R-568. 

Finally, Bertrand et al. have developed a highly efficient chemoenzymatic DKR of primary amines using a combination of lipase CALB and octanethiol... 

Reaction System Candida antarctica type B lipase (CalB)-catalyzed esterification of propionic add and 1-butanol in a water/w-decane two-phase system is carried out. Both substrates favor the aqueous phase. Butyl propionate, which is formed as the product, has a partitioning coeffident favoring the organic phase. Selective extraction of the ester from the aqueous phase prevents the reaction to reach equilibrium. 

Racemization of the remnant substrate in a DKR process can be performed either spontaneously or by the employment of a chemo- or biocatalyst, which must be compatible with the reaction conditions used for the KR reaction. In the case of sec-alcohols, most of successful DKRs have been carried out by the use of ruthenium complex catalysts, soluble in the organic reaction media, which promote racemization through redox processes. The first examples describe the resolution of 1-phenylethanol (rac-1) by the combination of a rhodium catalyst (Rh2(OAc) ) with Pseudomonas fluorescens lipase [22], although more effective results were afforded by Backvall and coworkers [23], who developed the DKR of the same substrate and derivatives catalyzed by Candida antarctica lipase (CALB) and a ruthenium complex (Shvo s catalyst, 2 (Figure 14.2)), affording excellent conversions and enantiomeric excess (ee) values [24]. 

Nuijens et al. explored the use of subtilisin cross-linked enzyme aggregates and lipase for the activation of amino acids and peptides to obtain acyl donors for coupling reactions. This included amidation [104], and conversion to esters by attachment of the carboxamidomethyl (Cam) or trifluoroethyl (Tfe) group [11-13]. Interestingly, the esters could be formed and coupled to peptides by the same alcalase. Ester synthesis could also be catalyzed by lipase (CalB), and esterification and peptide bond formation could be catalyzed in the same reaction mixture. In these coupled reactions, the best results were obtained with a mixture of CalB and subtilisin. 

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