Ester hydrolysis regioselectivity

Applications of lipases include ester hydrolysis, regioselective acylation or deacylation, interesterification, and resolution of racemic mixtures. Such reactions can be employed in conjunction with a variety of substrate types, ranging from glycerol derivatives to organometallics [6]. Consequently, lipases can be utilized in a range of industries, including the manufacture of... 

The Schmidt rearrangement of optically active a,a-bisalkylated 3-keto esters (161) regioselectively proceeds to give N-acyl a-alkylated a-amino acid esters (162) with retention of configuration and little or no racemization." Acid hydrolysis of (162), followed by treatment with propylene oxide, affords a-alkylated a-amino acids (163) in high yield and optical purity (equation 48). 

It is important to emphasize at this point that the stereochemical outcome of hydrolyses by epoxide hydrolases is, in theory, somewhat more complicated to analyze than a normal ester hydrolysis for example. This is due to the fact that, for a racemic substrate, each of the two enantiomers can of course react with different kinetics but also different regioselectivities, leading, in certain cases, to quite puzzling results. This problem, which may lead to erroneous interpretations as well as to wrong E value calculations, has been addressed by the two groups mentioned above [176, 177]. A detailed description of such different stereochemical outcomes, as well as of a new method allowing for the determination of the regioselectivity of the enzymatic attack on both enantiomers, has been described very recently [ 178]. 

The oxidation of the cyclic enol ether 93 in MeOH affords the methyl ester 95 by hydrolysis of the ketene acetal 94 formed initially by regioselective attack of the methoxy group at the anomeric carbon, rather than the a-alkoxy ketone[35]. Similarly, the double bond of the furan part in khellin (96) is converted ino the ester 98 via the ketene acetal 97[l23],... 

Methylbenzotriazole derivatives with an aminoethylene substituent in position 4 also regioselectively produce only the angularly annelated 7-ethoxycarbonyl-6-0X0-6,9-dihydro-2-methyl-2//-triazolo[4,5-/i]quinoline 158. Under alkaline hydrolysis the ester 158 yielded the corresponding acid 159 (90CCC1038, 92FA1001). 

The (S )-valine based bislacdm ether adds regioselectively in a 1,6-fashion to a,/ -y,<5-unsat-urated -substituted esters with both simple and induced diastereoselectivity exceeding 99 1. This provides, after hydrolysis, virtually enantiomerically pure dimethyl ( )-2-amino-3-hep-tene-l,7-dioates 206. 

In some cases enzymes can increase the rate of reaction by up to lO times. Carnell and Roberts (1997) have briefly discussed the scope of biotransformations that are used to make pharmaceuticals like penicillins, cephalosporines, erythromycin, lovastatin, cyclosporin, etc., and for food additives like citric acid, L-glutamate, and L-lysine. A very successful transformation by Zeneca has been that of benzene reduction, with Pseudomonase Putida, to dihydrocatechol and catechol the dihydro derivative is used to produce (+/-) pinitol. Fluorobenzene has been converted to fluorodihydrocatechol, an intermediate for pharmaceuticals. The highly stereo selective Bayer-Villeger reaction has been carried out with genetically engineered S-cerevisvae. Hydrolases have allowed enantioselective, and in some cases regioselective, hydrolysis of racemic esters. 

Carbonyl compounds, such as aldehydes [103, 179], (thio)ketones [31, 94, 180-183], carboxylic acids, and esters [183, 184] with 1 are reduced to alcohols after hydrolysis [5], except in stericaUy hindered cases (see Section 8.5) [185, 186]. Under the same experimental conditions the regioselective reduction of the oxirane ring with 1 gives also the corresponding alcohol [183, 187]. 

R = Me, Et, and PhCH2, respectively Fig. 8.1). In 80% human plasma at pH 7.4 and 37°, these model prodrugs were hydrolyzed with tm values of 3.5, 16, and 2.6 min, respectively [59]. Such rates of enzymatic hydrolysis are comparable to those of various carbamoylmethyl esters of benzoic acid (Table 8.2). It is important to note that the direct liberation of benzoic acid by Reaction a (Fig. 8.1) was severalfold faster than the competitive Reaction b. Reaction c was very slow in human plasma (tm > 100 h). In HO -catalyzed hydrolysis, the opposite regioselectivity was seen, with the terminal ester bridge being cleaved markedly faster than the central one. No data appears to be available on chemical hydrolysis at neutral pH. 

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