Meso cyclic diesters

Lactide (LA), the cyclic diester of lactic acid, has two stereogenic centers and hence exists as three stereoisomers L-lactide (S,S), D-lactide (R,R), and meso-lactide (R,S). In addition, rac-lactide, a commercially available racemic mixture of the (R,R) and (S,S) forms, is also frequently studied. PLA may exhibit several stereoregular architectures (in addition to the non-stereoregular atactic form), namely isotactic, syndiotactic, and heterotactic (Scheme 15). The purely isotactic form may be readily prepared from the ROP of L-LA (or D-LA), assuming that epimerization does not occur during ring opening. The physical properties, and hence medical uses, of the different stereoisomers of PLA and their copolymers vary widely and the reader is directed to several recent reviews for more information.736 740-743... 

The production of S5mdiotactic PLA starts with a cyclic dimer of lactic acid, meso-lactide, i.e., the cyclic diester of lactic add, which has two centers of asymmetry with the opposite configurations R and S. Meso-lactide is shown in Figure 3.1. 

G. Sabbioni, J. B. Jones, Enzymes in Organic Synthesis. 39. Preparations of Chiral Cyclic Acid-Esters and Bicyclic Lactones via Stereoselective Pig Liver Esterase Catalyzed Hydrolyses of Cyclic meso Diesters ,./. Org. Chem. 1987, 52, 4565 - 4570. 

In addition to cyclic allylic substrates, malonate nucleophiles have been used in reactions with both symmetrical" and unsymmetrical" acyclic systems, and with geminal dicarboxylates. Malonates and Meldrum s acid have also been used as nucleophiles in the desymmetrization of meso diesters. 

The asymmetric hydrolysis of several cyclic meso-diesters has been accomplished and optically pure monoesters have been obtained. A classical example is the hydrolysis of dimethyl cis-4-cyclohexene-1,2-dicarboxylate, which affords the corresponding nearly optically pure half ester, a versatile synthon for various chiral cyclohexane derivatives (eq 3). ... 

Similarly, the two chemically identical groups X, positioned on carbon atoms of opposite (/ ,5)-configuration in a weso-substrate, can react at different rates in a hydrolase-catalyzed reaction (Scheme 2.4). So, the optically inactive meso-substrate is transformed into an optically active product due to the transformation of one of the reactive groups from X into Y along with the destruction of the plane of symmetry within the substrate. Numerous open-chain or cyclic c/s-weso-diesters have been transformed into chiral monoesters by this technique [30]. Again, for dicarboxylates the reaction usually stops after the first step at the carboxylate monoester stage, whereas two hydrolytic steps are usually observed with diacetoxy esters [31]. The theoretical yield of chiral product from single-step reactions based on an enantioface or enantiotopos differentiation or a desymmetrization of meso-compounds is always 100%. 

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