Esterification enantioselective

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]. 

To a much smaller extent non-enzymic processes have also been used to catalyse the stereoselective acylation of alcohols. For example, a simple tripeptide has been used, in conjunction with acetic anhydride, to convert rram-2-acctylaminocyclohexanol into the (K),(R)-Qster and recovered (S),(S)-alcohol[17]. In another, related, example a chiral amine, in the presence of molecular sieve and the appropriate acylating agent, has been used as a catalyst in the conversion of cyclohexane-1(S), 2(/ )-diol into 2(S)-benzoyloxy-cyclohexan-1 f / j-ol1 IS]. Such alternative methods have not been extensively explored, though reports by Fu, Miller, Vedejs and co-workers on enantioselective esterifications, for example of 1-phenylethanol and other substrates using /. vo-propyl anhydride and a chiral phosphine catalyst will undoubtedly attract more attention to this area1191. 

Burgess, K. Jennings, L. D. Enantioselective esterifications of unsaturated alcohols mediated by a lipase prepared from Pseudomonas sp. J. Am. Chem. Soc. 1991,113, 6129-6139. 

Hexane Enantioselective esterification of Menthol with several anhydrides [128]... 

Isooctane (glucose based Enantioselective esterification of 2-Octanol and [59]... 

Enzymes such as pig liver esterase have been successfully applied in enantioselective hydrolysis of allenyl esters on a scale of 2 mmoles131. This provides the enantiomerically enriched allene-carboxylic acid as well as the ester of opposite configuration, by what is in fact a catalytic kinetic resolution (6-90% oy). Conversely, partial enantioselective esterification of /1-hydroxy-allenes (3-72% oy) employing lipases has been reported132,133. 

Figure 10.12 Enantioselective esterification of 2-substituted propanoic acids.

The enantioselective esterification of 2-arylpropionic acids catalysed by a lipase was discussed earlier.26 Steady-state kinetics of the Pseudomonas cepacia lipase-catalysed hydrolysis of five analogous chiral and achiral esters (R)- and (.S )-(235 R1 = Me, R2 = H), (R)- and (reaction mixtures of water-insoluble substrates.212 The Km values were all die same and the apparent kcat values reflected the binding abilities of the alcoholate ions for the fast-reacting enantiomers. All the substrates are believed to be... 

Enantioselective enzymatic esterifications represent a further type of biotransformation that has been used for the synthesis of optically active organosilicon compounds. The first example of this particular type of bioconversion (kinetic racemate resolution) is illustrated in Scheme 22. Starting from the racemic l-silacyclohexan-2-ol rac-43, the optically active 5-phenylpentanoate (S)-94 was prepared by enantioselective esterification with 5-phenylpentanoic acid using 2-methylheptane as solvent and crude Candida cylin-dracea lipase (CCL E.C. 3.1.1.3) as biocatalyst7. The enantiomeric purity of (S)-94 was ca 65% ee (bioconversion not optimized). 

Enzymatic kinetic resolutions via enantioselective esterifications have been successfully used for the preparation of optically active (hydroxymethyl)silanes, with the silicon atom... 

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. 

Rantakyla, M. Aaltonen, O. Enantioselective Esterification of Ibuprofen in Supercritical Carbon Dioxide by Immobilized Lipase. Biotechnol. Lett. 1994, 16, 825-830. 

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

Various lipases and esterases have been used for the enantioselective esterification of alcohols and hydrolysis of esters. For example, Burkholderia cepacia lipases (PS, Amano Enzyme Inc.) and Candida antarctica lipase (CAL, Novozymes) have been widely used for its wide substrate specificities, high activities and chemo, regio and enantioselectivities. Fundamentals and some selected applications are shown in this section. The origins and abbreviations of lipases introduced here are as follows. 

Dynamic kinetic resolutions of secondary alcohols and amines have been achieved by the combination of biocatalysts with metal catalysts.12 For example, a metal catalyst was used to racemize the substrate, phenylethanol, and a lipase was used for the enantioselective esterification as shown in Figure 12. The yield was improved from 50% in kinetic resolution without racemization of the substrate to 100% with metal catalyzed racemization. 

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]. 

The enantioselective esterification of (R,S)-2-phenylpropanoic acid in organic solvent was studied by using dry myceUa of A. oryzae MIM and R. oryzae CBS... 

Scheme 6.1 Enantioselective esterification of (R,S)-fiurbiprofen with 1-octanoi.

Subsequent studies by Morihara s group established that it was possible to obtain chiral selective catalysts as well [51,52]. Enantioselective esterification was observed for amino acid derivatives and chiral amines. 

An enzyme-catalyzed enantioselective esterification of racemic LA 3 with -alcohols containing one to eight carbon atoms in hexane as a solvent, using Candida rugosa lipase <1997TA337>, has been described (Scheme 24). The best selectivity at 30% conversion was obtained with -hexanol, yielding the (3)-ester 176 with 72% ee, along with (K)-lipoic acid (20% ee) this decreased with -octanol (58% ee for an ester and 24% for acid) and there was a drastic drop... 

A preparatively useful synthesis of (R)-lipoic acid involves Baeyer-Villiger monooxygenase-catalyzed biotransformation of 2-(2-acetoxyethyl)cyclohexanone 351 to the key precursor, that is, chiral lactone 352 (Scheme 68) < 1997BMCL253, 1995CC1563>. The enzyme-catalyzed lactone 352 was then converted by a standard reaction procedure into the desired acid on enantioselective esterification of racemic lipoic acid, using C. rugosa lipase. 

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. 

Rantakyla M, Aaltonen O. Enantioselective esterification of ibuprofen in supercritical carbon dioxide by immobilized lipase. Biotechnol Lett 1994 16 825-830. 

Enantioselective esterification can be pressure dependent in supercritical fluoroform. For example, the selectivity of the transesterification of A -acetyl-phenylalanine ethyl ester with methanol catalyzed by Subtilisin Carlsberg was shown by Kamat et al. (26) to be greater at higher pressures than at lower pressures [Eq. (9)] ... 

Mori T, Funasaki M, Kobayashi A, Okahata Y. Reversible activity changes of a lipid-coated lipase for enantioselective esterification in supercritical fluoroform. Chem Commun, 2001 1832-1833. 

Martins JF, de Carvalho IB, de Sampaio TC, Barreiros S. Lipase-catalyzed enantioselective esterification of glycidol in supercritical carbon dioxide. Enzyme Microb Technol 1994 16 785-790. 

Ionic liquids have also been used as reaction media in biocatalytic esterification reactions. In this context, the enantioselective esterification of 2-substituted-pro-panoic acids with 1-butanol catalysed by CrL in ionic liquids has been carried out by Ulbert et al. [76] (Fig. 7.10). It was demonstrated that application of [hmim+] [PF ] and [onim ][PF ] ionic hquids was beneficial from not only enzyme activity... 

Yuan Y, Bai S, Sun Y (2006) Comparison of Upase-catalysed enantioselective esterification of (9)-menthol in ionic liquids and organic solvents. Food Chem 97 324-330... 

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