James J. Bergan

The enantioselective synthesis of LTD4 antagonist L-708,738

Abstract An efficient, 9-step synthesis of LTD 4 antagonist L-708,738 is described. The asymmetric center is set via a chiral borane reduction.

A convergent synthesis of a novel non-peptidyl growth hormone secretagogue, L-692,429

Abstract A practical, convergent synthesis of L-692,429 (1) from three key intermediates - the 3- aminobenzlactam 2, the β-lactam 3 and the biphenyltetrazole 4 is described. The mechanism of the coupling reaction in which 3 is used as a β-aminoacid equivalent is also presented.

A practical chemoenzymatic synthesis of an LTD4 antagonist

Abstract Enzymatic asymmetrization of a prochiral diester having 4 bonds between the ester group and prochiral center is the cornerstone of a short and efficient synthesis of an LTD4 antagonist. The enzymatic hydrolysis occurs in a heterogeneous slurry, but a kinetic analysis shows that the reaction takes place in solution. Product inhibition of the enzyme is severe, requiring that a substantial amount of enzyme be used relative 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.

Enzymes and practical asymmetric synthesis

A practical, chemoenzymatic, four-step synthesis of the LTD4 antagonist MK-0679 is described. The key steps are enzymatic hydrolysis of the prochiral diester to the ester-acid in 99% enantiomeric excess followed by aluminum mediated amidation of the methyl ester to afford MK-0679 in high overall yield. This synthesis is superior to the synthesis of the racemate MK-0571.