Synthesis of a transition-state analog for the hydrolysis of the zearalenone lactone

The development of a catalytic antibody for the hydrolysis of the lactone functionality in zearalenone (1) is viewed as a potential solution to animal fertility problems associated with the estrogenic mycotoxin. A phosphonomacrolactone is proposed as a hapten for the generation of such antibodies. A suitably functionalized aryl phosphonic acid 4 was condensed with the racemic aliphatic fragment 5 via a Mitsunobu reaction. Macrocyclic formation was achieved via RCM to give advanced intermediate 23, a phosphonate analog of zearalenone, ready for deprotection and conjugation to a carrier protein.