Irreversible lipase-catalyzed secondary alcohols

Lipase-Catalyzed Irreversible Transesterification of Secondary Alcohols... 

The low-temperature method has been applied to some primary and secondary alcohols (Fig. 1) For example, solketal, 2,2-dimethyl-1,3-dioxolane-4-methanol (3) had been known to show low enantioselectivity in the lipase-catalyzed resolution (lipase AK, Pseudomonas fluorescens, E = 16 at 23°C, 27 at 0oc) 2ia however, the E value was successfully raised up to 55 by lowering the temperature to —40°C (Table 1). Further lowering the temperature rather decreased the E value and the rate was markedly retarded. Interestingly, the loss of the enantioselectivity below —40°C is not caused by the irreversible structural damage of lipase because the lipase once cooled below —40°C could be reused by allowing it to warm higher than -40°C, showing that the lipase does not lose conformational flexibility at such low temperatures. 

Kinetic Resolution by Transesterification. Asymmetric transformation involving acylation of chiral alcohols is by far the most common example of kinetic resolution by lipase-catalyzed transesterification, most commonly with irreversible vinyl esters. This field is now becoming the most widely applied technique involving lipases. Recent reports of the numerous secondary alcohol substrates include various monocyclic (eq 6) andacyclic compounds, cyanohydrins, sulfones, and glycals, to name a few. 

Special attention should be devoted to less conventional applications of the enzymatic transesterification methodology such as resolution of unstable substrates as racemic secondary hydroperoxides [291]. The development of new reactions in the presence of enzymes should pursued, as, for example, the simultaneous formation of a hemithioac-etal and die irreversible transesterification in the presence of a lipase [292]. Also, for synthetic applications, the combination of enzymatic and chemical asymmetrical methods could lead to interesting results, such as the one-pot lipase-catalyzed acylation and the Mitsonobu inversion of the configuration of the unreacted alcohol, which should lead to only one enantiomeric ester [293]. 

---