Practical Synthetic Method of (2Z,3E)-1,4-Diphenylbutadiene T-2639, an Inhibitor of Plasminogen Activator Inhibitor-1 (PAI-1) Production

A practical synthetic method of (2Z,3E)-1,4-diphenylbutadiene derivative T-2369 (1), a potent inhibitor of plasminogen activator inhibitor-1 (PAI-1) production, is described. Conditions of Stobbe condensation in the conventional synthesis of T-2369 were examined, and a new method to efficiently synthesize the key intermediate, (2Z,3E)-2,was derived. (2Z,3E)-2 was selectively obtained in 82% (with 91:9 selectivity) by predominant precipitation of (2Z,3E)-2 Na salt and in situ isomerization of (2E,3E)-2 to (2Z,3E)-2.