Although the substrate scope of PLE is broad, enantioselectivity varies as a function of the structure of the substrate. This section describes substrates that are hydrolyzed by PLE with the highest enantioselectivity, as well as sensitive substrates that may be hydrolyzed to achiral carboxylic acids in high yield without side reactions.
Glutarates were the first substrates to be hydrolyzed with PLE in high enantioselectivity. Although yields are moderate, enantioselectivity is extremely high.
3-Alkyl glutarates with small alkyl substituents are hydrolyzed to the (R)-monoester; however, when a large alkyl substituent is present, the (S)-monoester forms. This switch in enantioselectivity is accurately predicted by the active site model given above.
An opposite trend is observed in desymmetrizing hydrolyses of 2-methyl malonates, which afford the (S) enantiomer when the other substituent on C-2 is small, and the (R) enantiomer when the other C-2 substituent is large.
A number of meso diesters other than the substrates described above may be hydrolyzed by PLE with high enantioselectivity. Cyclic meso diesters tend to be hydrolyzed more selectively than acyclic diesters. The predominant enantiomer of product depends on ring size.
7-Oxabicyclo[2.2.1]heptane-2,3-dicarboxylates are an interesting class of diesters that are hydrolyzed by PLE with high enantioselectivity. These substrates have been used for the enantioselective construction of biologically relevant sugars (see Synthetic Applications below).
Racemic mixtures of all of the substrates described above, as well as additional chiral diesters (such as the epoxy ester in equation (8)), may be resolved using PLE for kinetic resolution. A significant disadvantage of kinetic resolution is a maximum yield of hydrolyzed product of 50%. However, if rapid racemization is occurring alongside hydrolysis (an example of dynamic kinetic resolution), a maximum yield of 100% is possible.
Esterase enzymes may also be used for hydrolysis of base-sensitive monoesters. PLE has been applied to the synthesis of prostaglandins for the selective hydrolysis of the ester without destruction of the β-hydroxy ketone moiety.