Synthesis of (E)- and (Z)-29-methylidyne-2,3-oxidosqualene derivatives as inhibitors of liver and yeast oxidosqualene cyclase

Abstract

The synthesis of (E)- and (Z)-29-methylidyne-2,3-oxidosqualene derivatives is described starting from the C₂₂ and C₁₇ squalene aldehyde monobromohydrins. The conversion was achieved by means of a Wittig reaction, followed by desilylation of the terminal acetylene. For trisubstituted 1,3-enynes, preliminary alkylation with a suitable allyl bromide was performed. A new procedure for the synthesis of squalene aldehyde C₂₇, C₂₂ and C₁₇ monobromohydrins is also described. Some of the new compounds behaved as inhibitors of pig liver and yeast oxidosqualene cyclase and were time-dependent inhibitors of the animal enzyme.