Transition-State-Stabilized Macrolide Closures

Article abstract of DOI:10.1021/jo01296a046

Thiol-functionalized crown ethers serve as reagents for macrolide closures.The thioesters derived from these crown ethers and ω-hydroxy carboxylic acids yield macrolides when treated with potassium tert-butoxide.The reaction proceeds via a templated conformation in which the ω-alkoxide is held proximate to the thioester through ionic bonding to the crown-bound potassium cation.Variations in crown ether structure show that the criterion of proximate binding is necessary but not sufficient to ensure efficient macrolide closure.The optimal crown ether reagent provides transition-state stabilization for the attack of the alkoxide on the thioester carbonyl by situating the carbonyl oxygen immediately adjacent to the crown-bound potassium cation.