Enzyme catalysed hydrolysis of dialkylated propanedioic acid diesters, chain length dependent reversal of enantioselectivity

Björkling, Fredrik; Boutelje, John; Gatenbeck, Sten; Hult, Karl; Norin, Torbjörn; Szmulik, Peter

doi:10.1016/s0040-4020(01)96536-6

Cited by 97 publications

(65 citation statements)

References 7 publications

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“…It now is mainly the (pro-R)-ester group which undergoes hydrolysis. Similar changes of conformations, which are due to the increasing site of the substituents, have been observed in the past in the case of esters of malonic acid [34], aminoglutaric acid [35-371, and of a series of monocyclic diesters [15] [38]. These results indicate that, in the centre of activity of PLE, two additional binding sites of variable size are present besides both regions which bind the hydrolyzed and the non-hydrolyzed ester groups.…”

Section: Substrate Productsupporting

confidence: 81%

Stereoselective Hydrolysis of Substituted Cyclopropanedicarboxylates with Pig Liver Esterase

Walser¹,

Renold²,

N'Goka³

et al. 1991

Helvetica Chimica Acta

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The hydrolysis of the rneso-cyclopropane-l,2-dicarboxylates la-3a, 4, 5a, 6a, and 9, containing various substituents at C(3), and of the rac-3-phenylcyclopropane-1,2-dicarboxylates 7a, Sa, and 10 with pig liver esterase (PLE) is described. The stereoselectivity and absolute configurations of the products were determined. An interpretation of results was attempted on the basis of a recent active-site model for PLE.Introduction. -The efficient synthesis of biologically active compounds, either of natural or unnatural origin, frequently requires chiral synthons. Enzymes as chiral catalysts are now widely used for their preparation [l-41, because it often is rather difficult to introduce centres or chirality or perform regiospecific transformations by the application of purely 'chemical methods'. Especially esterases, such as pig liver esterase (PLE, E.C. 3.1.1.1), a serine hydrolase, have been studied extensively in recent years [5-81. We have used PLE successfully in resolving racemic esters [9] and for the preparation of versatile chirons [5] [6] [9] [lo]. Stability, low costs, and the ability of hydrolyse a wide range of substrates with high stereoselectivity represent additional advantages of this enzyme which operates-without the need for co-enzymes. Until now, more than one hundred different esters, mainly meso-and prochiral-diesters have been subjected to the treatment with PLE [8]. To be able to fully exploit the potential of this enzyme, it is indispensable to understand the factors which are responsible for the specificity. Accordingly, we as well as other research groups have initiated investigations for securing a large number of data on hydrolyses, allowing to gain more insight into the relationship between substrate structure and enzymic activity of PLE. Until recently, it appeared to be very difficult to reach this goal, not only because the physiological role of PLE is unknown [ 1 I], but also because commercially available PLE preparations are mixtures of at least six isoenzymes [12] [ 131 which, however, were found to exhibit essentially the same stereospecificity [14]. These findings justify the attempt to rationalize the results of the hydrolyses by an active-site model which is mainly based on the measured ee values and the absolute configuration of the hydrolysis products. Several approaches to such a model have been reported [14-181. The most recent proposal made by Jones and coworkers which is based on cubic-space descriptors, is at present the most precise published active-site model [19].Here, we report on the results of the hydrolysis of a series of structurally related cyclopropane-l,2-~arboxylates with PLE. These substrates were chosen for the following reasons: I ) The cyclopropane ring provides rigidity. Therefore, only one preferred conformation has to be accounted for the analysis of the substrate/active-site interac-

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Section: Substrate Productsupporting

confidence: 81%

Stereoselective Hydrolysis of Substituted Cyclopropanedicarboxylates with Pig Liver Esterase

Walser¹,

Renold²,

N'Goka³

et al. 1991

Helvetica Chimica Acta

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“…MOPS buffers (Aldrich 99%) also contained 100 mM NaCl (J. T. Baker, Baker analyzed) and 10 mM CaCl 2 (E. Merck, pro analysis). DMBMM was prepared according to Björkling et al (1985a) by alkylation of dimethyl methylmalonate (99%, Aldrich) with benzyl bromide (98%, Aldrich) with 60% yield. Purity was >99% (GC).…”

Section: Methodsmentioning

confidence: 99%

Simple dissolution-reaction model for enzymatic conversion of suspension of solid substrate

Wolff

Zhu

Kielland

et al. 1997

Biotechnol. Bioeng.

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“…Durch Hydrolysc von alkylierten Methylmalonsiiure-estern mit Schweineleberesterase (PLE) oder a-Chymotrypsin als Katalysator erhielten Bjiiukling et al die Monoester in massiger bis guter Enantiomerenreinheit [9]. Katsuki und Mitarbeiter haben ein chirales a-Cyanoessigsaure-Derivat dialkyliert [lo]; nach Hydrolyse wurden Produkte von 80-90°/" ee isoliert.…”

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Elektrochemische Oxidation von (S)‐Äpfelsäure‐Derivaten: ein Weg zu enantiomerenreinen alkylierten Malonaldehydsäure‐estern

Renaud¹,

Hürzeler²,

Seebàch³

1987

Helvetica Chimica Acta

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Electrochemical Oxidation of (S)-Malic-Acid Derivatives: a Route to Enantiomerically Pure Alkylmalonaldehydic EstcrsThe ?.?-di;ilkylinalic-acid diesters. prepared by the pi-eviously described diastereosclective alkylations through dilithiinn alkoxitic enolatea, ;ire s.ipoiiitled to thc rnonomtci-s conlaininp a free a-hydroxycarhoxylic-acid moiety iSdrm7c 31. The monoesters arc suhjected to electl-ocheinical oxidative decarboxy1,ition in MeOH. If the Intermediate monoacids ;ire purified, the iiialonclldchydic esters (2-forinyl-2-alkyIcarboxyl;iles) obraincd by this proccdure are enantioinerically pure; thcy have the s;iine sIructural features, i.t,. two cnantiotopic functionrili.mi branches on the (pcrsuhstituted) stercogenic center, iis the well known 3-hydroxy-2-nicthylpropaiioic acid ('Rorlir acid') which war employed frequently as il starting material f'or the prepar;ition of cither enantioiner of various target inolecules.Einleitung. ~ In1 Rahmen unserer Arbeit iiber die Rereitstellung von chiralen, nicht racemischen Synthcse-Bausteineii haben wir schon uber die elektrochemische Oxidation von P-Hydroxycarbonsiiurcn [ 11 und von cc-Aminocarbonsauren [2] berichtet. Wir be-

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Enzyme catalysed hydrolysis of dialkylated propanedioic acid diesters, chain length dependent reversal of enantioselectivity

Cited by 97 publications

References 7 publications

Stereoselective Hydrolysis of Substituted Cyclopropanedicarboxylates with Pig Liver Esterase

Stereoselective Hydrolysis of Substituted Cyclopropanedicarboxylates with Pig Liver Esterase

Simple dissolution-reaction model for enzymatic conversion of suspension of solid substrate

Elektrochemische Oxidation von (S)‐Äpfelsäure‐Derivaten: ein Weg zu enantiomerenreinen alkylierten Malonaldehydsäure‐estern

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