Candida antarctica lipase CALA

The rather complex furylvinylcarbinol derivative 76 shown in Scheme 4.28 was required in enantiopure form as a key intermediate in the synthesis of the natural product cneorin. The carbinol moiety is heavily substituted with sterically demanding groups. Therefore attempts to resolve the furylvinylcarbinol with CALB or lipase PS-II led to very slow reactions. However, the rarely used enzyme Candida antarctica lipase A (CALA), which is known to act on sterically hindered substrates offers an alternative. Thus acylation of the furylvinylcarbinol 76 with 2,2,2-trifluoroethyl butanoate catalyzed by CALA (immobilized on celite with sucrose at pH 7.9) furnished the enantiomerically enriched propanoate of S-76 and R-76 (Scheme 4.28) [90]. Small-scale experiments gave E > 300. 

Tertiary alcohols are very unreactive toward hydrolases. There are, however, exceptions. Some enzymes have a certain amino acid motif located in the oxyanion binding pocket that allows the docking of space-demanding alcohols such as tertiary ones into the acylated enzyme [104]. One such hydrolase is Candida antarctica lipase A (CALA), which has been found to catalyze the acylation of the tertiary 2-phenyl-3-butyn-2-ol rac-110 by vinyl acetate in organic solvents. Thus efficient resolution of 110 was achieved in isooctane at room temperature (Scheme 4.34) [105]. 

Scheme 4.39 Candida antarctica lipase A (CALA)-catalyzed ...

Candida antarctica lipase A (CaLA), which was ten times more active in [BMPy][BF4] and [BMIm][ Tf2N] than in diisopropyl ether (DIPE) [54] is an exception. 

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. ... 

The application of ionic liquids in lipase biocatalysis has not remained entirely restricted to CaLB, PcL or CrL. Other lipases have been used in ionic liquids for ester synthesis such as Candida antarctica lipase A (CaLA) [15,16], Thermomyces lanuginosus lipase [17] (TLL), Rhizomucor miehei lipase (PmL), Pseudomonas fluorescens lipase (PJL) [18], Pig pancreas lipase (PpL) [17] and Alcaligenes sp. lipase (A5 L) [16]. 

In the same area, the DKR of p-amino esters, including aliphatic, aromatic as well as heteroaromatic ones, was performed hy Backvall et al, using a palladium nanocatalyst [Pd°/AlO(OH)] in combination with immobilised Candida antarctica lipase A (CALA/GAmP-MCF), providing the corresponding chiral amides in both excellent yields and enantioselectivities, as shown in Scheme 8.75. ... 

More recently, interest in the immobilization of catalysts has increased. Candida antarctica lipase A (CALA) immobilized in mesoceUular foam (MCF) showed a dramatic increase in the enantioselectivity, as well as an improved thermostability of the enzyme. The immobilized enzyme (CALA/GAmp-MCF) was combined with the para-methoxyphenyl derivative of the Shvo catalyst, in an efficient DKR of 3-amino-3-phenylpropanoate at 90°C (24) [90]. The chiral acy-lated p-amino ester was obtained in 85% yield and with an ee value of 89%. 

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]. 

---