In order to gain a more detailed insight into the relationship between substrate structure and the stereoselectivity of the enzyme pig liver esterase (E.C. 3.1.1 .I .) a large series of mainly meso and prochiral diesters with an open chain or a cyclic structure has been studied and evaluated. Results obtained with 3substituted cyclopropane-l,2-dicarboxylates are incompatible with the three-dimensional (cubic) active-site model of PLE proposed by J.B. Jones et a/. Kinetic resolution of mesoand racemic diesters as well as of racemic monoesters has been observed. Their synthetic potential as versatile enantiomerically pure synthons for the construction of complex natural products is demonstrated by the synthesis of the pheromone endo1,3-dimethyI-2,9-dioxabicyclo[3.3.l]nonane, C(IS)-to-C(27)-Segment of rifamycin S and the C(1)to C(7)segment of 14-membered macrolide antibiotics. 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 (ref. 1-1 l ) , because it is often rather difficult to introduce centres of 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 .I.), a serine hydrolase, have been studied extensively in recent years (ref. 7, 12-15). 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 mesoand prochiral-diesters have been subjected to the treatment with PLE (ref. 7). 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 realtionship between substrate structure and enzymic activity of PLE. Commercially available PLE preparations are mixtures of at least six isoenzymes which, however were found to exhibit essentially the same stereospecificity (ref. 16). These findings justify the attempts 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. The following selected examples of results which were obtained by us and various other authors from mesodiesters in the malonate series appear to be very inconsistent and unpredictable with respect to the ee values and absolute configurations at first sight: