Lipase-catalyzed enantioselective

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). 

R)-3-Phenoxybutanoic acid and the corresponding butyl (S)-ester were obtained by Burkholderia cepacia lipase-catalyzed enantioselective esterification of the racemic acid with 1-butanol in hexane containing anhydrous sodium sulfate to remove the water produced during the reaction (Figure 6.17) [64]. 

A chemoenzymatic methodology has been developed using indium-mediated allylation (and propargylation) of heterocyclic aldehydes under aqueous conditions followed by Pseudomonas cepacia lipase-catalyzed enantioselective acylation of racemic homoallylic and homo-propargylic alcohols in organic media.192... 

K. Naemura, K. Kittaka, M. Murata, H. Ida, K. Hirose, Y. Tobe, Lipase-Catalyzed Enantioselective Alcoholysis of Enol Acetates Optical Resolution of Ketones and Aldehydes Using Lipases in Organic Solvents , Enantiomer 1996, 1, 219-222. 

In a succeeding publication, the same authors reported on an enantiose-lective approach to diquinane enones 6 and ent-6 by combining the above-described synthesis with an enzymatic kinetic resolution (Scheme 4) [12]. After lipase-catalyzed enantioselective transesterification of diol rac-12. 

The infrared radiation caused by the heat of reaction of an enantioselective enzyme-catalyzed transformation can be detected by modern photovoltaic infrared (IT)-thermographic cameras equipped with focal-plane array detectors. Specifically, in the lipase-catalyzed enantioselective acylation of racemic 1-phenylethanol (20), the (K)- and (S)-substrates were allowed to react separately in the wells of microtiter plates, the (7 )-alcohol showing hot spots in the IR-thermographic images (113,114). Thus, enantioselective enzymes can be identified in kinetic resolution. However, quantification has not been achieved thus far by this method, which means that only those mutants can be identified which have E values larger than 100 (113-115). 

Scheme 7.9 Resolution of racemic amines by lipase-catalyzed enantioselective amide formation (BASF).

The resolution of chiral amines via lipase-catalyzed enantioselective acylation is now a major industrial process, but interest in adopting ionic liquid reaction media has been surprisingly scant. Interestingly, acids could be used as the acyl donor (Figure 10.15) rather than the usual activated ester in a range ofionic liquids. CaLB was employed as the biocatalyst, and water was removed to shift the equilibrium toward the product [130, 131]. The highest rates were found in [BMMIm][TfO], [EMIm][TfO], and [EMIm][BF4]. 

M. Onaka, Efficient lipase-catalyzed enantioselective acylation in an ionic liquid solvent system. In Ionic Liquids as Green Solvents, R. D. Rogers, K. R. Seddon, Eds., ACS Symposium Series Vol. 856, ACS Washington D.C., 2003, p 251. 

H. Ebiike, and K. Achiwa, Drastic solvent effect on lipase-catalyzed enantioselective hydrolysis of prochiral 1,4-dihydropyridi-nes, Tetrahedron Lett. 1992, 33, 7157-7160. 

Martins, J. F. de Carvalho, I.B. de Sampaio, T. C. Barreiros, S. Lipase-Catalyzed Enantioselective Esterification of Glycidol in Supercritical Carbon Dioxide. Enzyme Microb. Technol. 1994, 16, 785-790. 

Figure 8 Lipase-catalyzed enantioselective acylation of 2-methoxy-2-phenylethanol (rac-1) using either vinyl acetate or isopropenyl acetate as acyl donor.

In the transesterification of (7 ,.S)-secondary alcohols, the (A)-alcohol was the faster reacting enantiomer yielding the (A(-acetate in high ee and leaving (.S )-alcohol as enantiomerically pure unreacted enantiomer. Trims-4-phenyl-3-butene-2-ol 29, another substrate pocessing an allylic strain has been successfully resolved on gram-scale via lipase-catalyzed enantioselective acylation of the alcohol and hydrolysis of its acetate.57... 

Figure 19 Lipase-catalyzed enantioselective hydrolysis of racemic 31) using phosphate buffer (pH =6) and...

Figure 22 Lipase-catalyzed enantioselective acetylation of l-azido-3-aryloxy-2-propanols 35.

Figure 24 Lipase-catalyzed enantioselective transesterification of 4-hydroxy-2-methyl-2-/>tolyl-cyclopentane-...

Figure 25 Lipase-catalyzed enantioselective hydrolysis of dZ-menthyl benzoate (dl-41).

Figure 29 Lipase-catalyzed enantioselective transesterification of 2-phenylbut-3-yn-2-ol 51.

A broad spectrum of racemic 2-hydroxy acids 65 were resolved via lipase-catalyzed enantioselective acetylation to their corresponding 2-acetoxy acids 66 using vinyl acetate as acyl donor in methyl Art-butyl ether as organic solvent. The unreacted enantiomer (R)-65 was recovered with ee values up to >99%.80... 

Inure et al94 reported the enzymatic resolution of trans-10-Azido-9-acetoxy-9,10-dihydrophenanthrene 111 in gram-scale using Candida cyclindracea lipase-catalyzed enantioselective hydrolysis in phosphate buffer. The substrate 111 (the ester) was obtained in 89 % yield and 83 % ee while the product 112 (the alcohol) was obtained in 90 % yield and 98 % ee. 

Figure 56 lipase-catalyzed enantioselective ring opening of unactivated alicyclic /J-lactams. 

Pchelka, K. B. Loupy, A. Plenkiewicz, J. Blanco, L. Resolution of racemic l-azido-3-aryloxy-2-propanols by lipase-catalyzed enantioselective acetylation. Tetrahedron Asymmetry 2000, 11,2719-2732. 

Shang, C-S. Hsu, C-S. Lipase-catalyzed enantioselective esterification of (S)-naproxen hydroxyalkyl ester in organic media. Biotechnology Letters 2003, 25 413-416. 

Adam, W. Lazams, M. Schmerder, A. Humpf, H-U, Saha-Moller, C. R. Schreier, P. synthesis of optically active e -hydroxy acids by kinetic resolution through lipase-catalyzed enantioselective acetylation. Eur. J. Org. Chem. 1998,2013-2018. 

Forro, E. Fulop, F. Lipase-catalyzed enantioselective ring opening of unactivated alicyclic-fused / lactams in an organic solvent. Organic Letters 2003, 5(8), 1209-1212. 

The use of extracellular lipases of microbial origin to catalyze the stereoselective hydrolysis of esters of 3-acylthio-2-methylpropionic acid in an aqueous system has been demonstrated to produce optically active 3-acylthio-2-methyl-propionic acid [41-43], The synthesis of the chiral side chain of captopril by the lipase-catalyzed enantioselective hydrolysis of the thioester bond of racemic 3-acetylthio-2-methylpropionic acid (15) to yield 5 -(-)-(15) has been demonstrated [44], Among various lipases evaluated, lipase from Rhizopus oryzae ATCC 24563 (heat-dried cells), BMS lipase (extracellular lipase derived from the fermentation of Pseudomonas sp. SC 13856), and lipase PS-30 from Pseudomonas cepacia in an organic solvent system (l,l,2-trichloro-l,2,2-tri-fluoroethane or toluene) catalyzed the hydrolysis of thioester bond of undesired enantiomer of racemic (15) to yield desired S-(-) (15), R-(+)-3-mercapto-2-methylpropionic acid (16) and acetic acid (17) (Fig. 8A). The reaction yield of... 

Lipase-catalyzed enantioselective ring cleavage of racemic cis- and rra r-13-azabicyclo[10.2.0]tetradecan-14-one has given enantiopure /3-aminoacids and /3-lactams (see Section 2.04.6.4) <2006TA3193>. 

A subfield in this area is using SCFs to control the stereoselectivity of biologically active chiral compounds. For example, supercritical CO2 has been used to do the lipase-catalyzed enantioselective esterification of ibuprofen. Enantiomeric purities exceeding 90% at an ibuprofen conversion of 25% have been reported [20]. 

In particular, the use of hydroxynitrile lyase has proved to be a general and reliable method for obtaining a-hydroxy nitriles of both configurations [22]. An interesting approach is the Upase- and baseacyl-cyanohydrin for a synthetic DKR [23]. This is a combination of two reaction systems the dynamic, base-catalyzed equiUbrium between acetone cyanohydrin, acetone, HCN, aldehyde and a racemic cyanohydrin and the lipase-catalyzed enantioselective and irreversible acylation of the hydroxyl group. The combination yields the... 

There are also recent reports of the lipase-catalyzed enantioselective hydrolysis of prochiral diacid derivatives such as 2-substituted malonates, barbiturates, and highly substituted, sterically hindered 1,4-dihydropyridine derivatives using acy-loxymethyl groups to enhance the reaction rate. An example of a prochiral diester hydrolysis is illustrated in eq 10. ... 

Lipase-catalyzed enantioselective esterification of racemic ibuprofen coupled with pervaporation... 

Won K, Hong JK, Kim KJ, and Moon SJ. Lipase catalyzed enantioselective esterification of racemic ibuprofen coupled with pervaporation. Proc. Biochem. 2006 41(2) 264—269. 

ATT. Yokomatsu. T.. Sato. M., and Shibuya. S., Lipase-catalyzed enantioselective acylation of prochiral 2-(co-phosphono)alkyl-L3-propanediols. Application to the enantioselective synthesis of m-phosphono-a-amino acids. Tetrahedron Asymmetry. 7. 2743, 1996. 

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