The Isoxazoline Route to the Hypocholesterolemic Agent Compactin: Use of the Isoxazoline as a 1,3-Diene Equivalent

Article abstract of DOI:10.1021/jo00392a009

A total synthesis of the hypocholesterolemic agent compactin is described in which the hexahydronaphthalene portion of this molecule is constructed by an intramolecular nitrile oxide cycloaddition reaction.In the context of this synthesis, the isoxazoline ring system was found to serve as a useful 1,3-diene equivalent.The protocol developed for this conversion involves transformation of the isoxazoline to an allylic alcohol followed by regioselective dehydration using aluminum oxide.Molecular mechanics calculations on compactin-related octahydronaphthisoxazoles are also presented.