Stereospecific synthesis of squalenoid epoxide vinyl ethers as inhibitors of 2,3-oxidosqualene cyclase

The stereospecific synthesis of squalenoid epoxide vinyl ethers with an isopentyloxy group is described. The synthesis involves the preparation of the C22 squalenoid aldehyde bromohydrin (15) by a new method via a one-step cleavage of lipophilic epoxides using periodic acid in diethyl ether, and the preparation of (1-isopentyloxyethyl)diphenylphosphine oxide (24). The structure of this compound has been confirmed by X-ray analysis. The configuration of vinyl ethers, synthesized using a Wittig-Horner reaction, has been determined by 13C n.m.r. Biological results show that vinyl ethers (5) and (27) are competitive inhibitors of 2,3-oxidosqualene cyclase from rat liver.