A PRACTICAL CHEMOENZYMATIC SYNTHESIS OF AN LTD4 ANTAGONIST

Enzymatic asymmetrization of a prochiral diester having 4 bonds betwee n the ester group and prochiral center is the cornerstone of a short a nd efficient synthesis of an LTD4 antagonist. The enzymatic hydrolysis occurs in a heterogeneous slurry, but a kinetic analysis shows that t he reaction takes place in solution. Product inhibition of the enzyme is severe, requiring that a substantial amount of enzyme be used relat ive to substrate. To more efficiently use the expensive enzyme, it was immobilized on several supports, the most effective of which was XAD 7 with crosslinked enzyme.