A Study of Stereoselective Hydrolysis of Symmetrical Diesters with Pig Liver Esterase

Abstract

SummaryPig liver esterase-(PLE) catalyzed hydrolysis of dimethyl esters of symmetrical dicarboxylic acids, including meso-diacids, cis-1,2-cycloalkanedicarboxylic acids, and diacids with a prochiral center, was studied with 14 substrates. The products of these stereoselective hydrolyses are chiral monoesters of dicarboxylic acids, with an enantiomeric excess (e.e.) from 10% to 100%. Some of these optically active monoesters are valuable synthons in natural products synthesis.An additivity pattern of a-and /3-substituents with the glutaric esters on the stereoselectivity of enzymatic hydrolysis was observed. Analysis of the experimental results leads to a model of enzyme stereoselectivity of diester hydrolysis in which the substitution pattern at a-and a-C-atoms is found to determine the absolute configuration of the resulting monoester.The control of absolute stereochemistry is of fundamental importance for natural product synthesis [l]. Although a plethora of chemical methods has been developed for the construction of optically active compounds [2], the unique opportunity provided by enzymes as catalysts in asymmetric synthesis is being increasingly exploited [3].It is theoretically possible, by utilizing the enantioselectivity of enzymes towards meso-compounds and compounds with a prochiral center to transform the total amount of starting material into a target molecule. The classical example of this kind of transformation represents the synthesis of (R)-mevalonolactone using the high selectivity provided by pig liver esterase (PLE) towards dimethyl 3-hydroxy-3-methylglutarate [4]. From a preparative standpoint it is important to note that by appropriate manipulation of the functional groups (S)-mevalonolactone can also be synthesized.We can envisage that by using enzymes which possess low substrate selectivity but which at the same time catalyze reactions with a high degree of stereoselectivity, a large number of new chiral synthons can be provided. a-Chymotrypsin [5], horse liver alcohol dehydrogenase [6], PLE [7], and some other esterases from different microorganisms [8] have already been used to provide chiral synthons of highest optical purity for the synthesis of natural products.

Crystal and molecular structure of cyclic sulfoxides: 2‐cyano‐2‐ethoxycarbonyl‐3,6‐dihydro‐4,5‐dimethyl‐2H‐thiapyran 1‐oxide and 2‐phenyl‐2‐methoxycarbonyl‐3,6‐dihydro‐2H‐thiapyran 1‐oxide

“…There are, however, some indications that may enable one to explain these differences in terms of the Tamm's model [9]. First of all, since the S = 0 and the alkoxycarbonyl groups are trans oriented both in l b and lc, the conformation adopted by each substrate seems to be of much greater importance.…”

“…Trying to find an explanation of the difference in reactivity of these substrates, we took into account a substrate model for pig liver esterase (PLE) proposed by Mohr et al [9]. According to this model, the optimal acceptance of the substrate by the enzyme takes place when a polar function and the reacting ester group are in a trans arrangement, and, in the case of cyclic substrates (particularly sixmembered ones), when the ester group occupies an equatorial position.…”

Synthesis of hydrophobic weak-acid monomers by enzymatic action and their polymerization to obtain hydrophobic polyelectrolytes

“…For n7, although the addition of a tensoactive compound increased the yield from 11 to 29% (Table 1), it was lower than the yield reported using LiI [11], PLE has been studied to catalyze hydrolysis of dimethyl esters of symmetrical dicarboxylic acids. The results show selective hydrolysis of only one of methyl esters [19,20]. Selectivity depends on the substituents of α-and β-C-atoms.…”

Synthetic Studies ond-Biotin, Part 8:[1] An Efficient Chemoenzymatic Approach to the Asymmetric Total Synthesis ofd-Biotinvia a Polymer-Supported PLE-Mediated Desymmetrization ofmeso-Symmetic Dicarboxylic Esters

“…[7] In particular, esterases, such as pig liver esterase (PLE), are now widely used in asymmetric organic synthesis, notably in the desymmetrization of meso compounds. [8] In this way, prochiral diesters can be hydrolyzed to enantiomerically enriched hemiesters in up to quantitative yield. [9] In 1982, Iriuchijima and co-workers [10] realized the first PLE-catalyzed asymmetric hydrolysis of prochiral diesters 3 into the corresponding (4S,5R)-hemiester 4 as a precursor for the formation of (3aS,6aR)-lactone 5 to perform an asymmetric total synthesis of 1.…”