Irreversible lipase-catalyzed transesterifications

In lipase-catalyzed transesterifications, frequent use of enol esters as acyl agents has been seen [1, 5], since the leaving unsaturated alcohol irreversibly tautomerizes to an aldehyde or a ketone, leading to the desired product in high yields. The polymerization of divinyl adipate and 1,4-butanediol proceeded in the presence of lipase PF at 45 °C [39]. Under similar reaction conditions, adipic acid and diethyl adipate did not afford the polymeric materials, indicating the high polymerizability of bis(enol ester) toward lipase catalyst. 

Kinetic Resolution by Transesterification. Asymmetric transformation involving acylation of chiral alcohols is by far the most common example of kinetic resolution by lipase-catalyzed transesterification, most commonly with irreversible vinyl esters. This field is now becoming the most widely applied technique involving lipases. Recent reports of the numerous secondary alcohol substrates include various monocyclic (eq 6) andacyclic compounds, cyanohydrins, sulfones, and glycals, to name a few. 

Lozano et al. [64—67], and Reetz, Leitner and co-workers [68, 69], simultaneously reported SCCO2-IL biphasic, biocatalytic systems for lipase-catalyzed transesterifications using vinyl esters as the transesterification agent [Eq. (13)]. Vinyl butyrate was used because the product vinyl alcohol tautomerizes to acetaldehyde and hence the reaction is irreversible. 

The lipase-catalyzed transesterifications described earlier are in general equilibrium reactions and a few methods have been proposed to make the reaction irreversible or to slow down the back reaction [120,121]. One approach consists of the use of trifluoroethyl esters as acylating reagents (Scheme 20). In this way trifluoroethanol is produced and the reverse reaction is slow, as the fluorinated alcohol is less nucleophile than ethanol [122]. 

The first 10-step total asymmetric synthesis of herbarumin III (42) in 24% overall was reported in 2004 by Gurjar and coworkers who later synthesized the compound using the RCM approach. Thereafter, a chemoenzymatic asymmetric synthesis of 42 which fixed the hydroxyl stereocenters (C7 and C9) by lipase catalyzed irreversible transesterification was described. 

Miyazawa, T. Kurita, S. Shimaoka, M. Ueji, S. Yamada, T. Resolution of racemic carboxylic acids via the lipase-catalyzed irreversible transesterification of vinyl esters. Chirality 1999, 11 554-560. 

Prochiral Compounds. The enantiodifferentiation of prochi-ral compounds by lipase-catalyzed hydrolysis and transesterification reactions is fairly common, with prochiral 1,3-diols most frequently employed as substrates. Recent reports of asymmetric hydrolysis include diesters of 2-substituted 1,3-propanediols and 2-0-protected glycerol derivatives. The asymmetric transesterification of prochiral diols such as 2-0-benzylglycerol and various other 2-substituted 1,3-propanediol derivatives is also fairly common, most frequently with Vinyl Acetate as an irreversible acyl transfer agent. 

Most of lipase-catalyzed acylations of sugars in organic solvents have been reported as transesterification rather than esterification reactions. The displacement of the equilibrium towards products has been accomplished by using activated acyl donors [58] such as 2,2,2-trichloroethyl esters and, more often, enol esters. The use of enol esters, such as a vinyl or an isopropenyl ester, was, in fact, first reported in lipase-catalyzed reactions with sugars [59]. In the reaction, an unstable enol is liberated which instantaneously tautomerizes to the corresponding aldehyde or ketone, making the reaction irreversible. 

W Adam, M Diaz, R Fell, C Saha-Moller. Kinetic Resolution of Racemic a-Hydroxy Ketones by Lipase-catalyzed Irreversible Transesterification. Tetrahedron Asymmetry 7 2207-2210, 1996. 

B. Lipase-Catalyzed Irreversible Transesterifications by Means of Vinyl Esters and Similar Reagents... 

Recently, 1-ethoxyvinyl acetate has been proposed as a novel and reliable acyl donor for the enzymatic resolution of alcohols (Scheme 24) in a lipase-catalyzed irreversible transesterification procedure [135]. A similar protocol has been utilized for the irreversible acetoacetylation of alcohols with diketene in the presence of lipases in organic solvents [136,137] and the reaction has been reported to proceed with high enantioselectivity [136], as shown in Scheme 25. 

Lipase-Catalyzed Irreversible Transesterification of Primary Alcohols... 

Special attention should be devoted to less conventional applications of the enzymatic transesterification methodology such as resolution of unstable substrates as racemic secondary hydroperoxides [291]. The development of new reactions in the presence of enzymes should pursued, as, for example, the simultaneous formation of a hemithioac-etal and die irreversible transesterification in the presence of a lipase [292]. Also, for synthetic applications, the combination of enzymatic and chemical asymmetrical methods could lead to interesting results, such as the one-pot lipase-catalyzed acylation and the Mitsonobu inversion of the configuration of the unreacted alcohol, which should lead to only one enantiomeric ester [293]. 

Irreversible Transesterification. A new preparation of chiral glycerol acetonide (2,2-dimethyl-l,3-dioxolane-4-methanol) involving an enantioselective hydrolysis of 2-0-benzylycerol diacetate to the (R)-monoacetate catalyzed by a lipoprotein lipase (47) has recently been developed. In an effort to prepare the (S)-enantiomer, we have used the aforementioned irreversible transesterification reaction using isopropenyl acetate as an acylating reagent, which upon reaction gives acetone as a... 

Regioselective acylations of polyhydroxylated compounds such as carbohydrates, glycerols, steroids, or alkaloids have been carried out with lipases, esterases, and proteases [13, 20]. One example is the Candida antartica lipase (immobilized on acrylic resin) catalyzed monoacylation of the signalling steroid ectysone (1) giving selectively the 2-C)-acetate 2 (eq. (1)). Using vinyl acetate for this transesterification the reaction was irreversibly pushed to the product side, since the liberated enol instantaneously isomerizes to acetaldehyde [21]. The sometimes unfavorable aldehyde is avoided when 1-ethoxyvinyl acetates [22], trichloro- or -fluoroethyl esters [23 a, b], oxime esters [23 c] or thioesters [23 d] are employed for the quasi-irreversible reaction courses. 

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