137846-76-5Relevant academic research and scientific papers
29-Methylidene-2,3-oxidosqualene derivatives as stereospecific mechanism-based inhibitors of liver and yeast oxidosqualene cyclase
Ceruti, Maurizio,Rocco, Flavio,Viola, Franca,Balliano, Gianni,Milla, Paola,Arpicco, Silvia,Cattel, Luigi
, p. 540 - 554 (1998)
Two pairs of isomers (18Z)- (8), (18E)-29-methylidene-2,3- oxidohexanorsqualene (21), and (18Z)-(31), (18E)-29-methylidene-2,3- oxidosqualene (34), have been obtained in a fully stereospecific manner, as inhibitors of rat and yeast oxidosqualene cyclase. A new method for the synthesis of C22 squalene aldehyde 2,3-epoxide is reported, as well as that of other 19-modified 2,3-oxidosqualene analogues. We found that the activity is the opposite in the two series: the (E)-hexanormethylidene 21 and the (Z)- methylidene 31 are potent and irreversible inhibitors of oxidosqualene cyclase, while (Z)-hexanormethylidene 8 and (E)-methylidene 34 are almost completely inactive. Reduction of the 18,19-double bond, such as in 39, eliminates the activity, while removal of both of the 19-linked groups such as in heptanor derivative 40 greatly reduces inhibition of the enzyme. (E)- Hexanormethylidene 21 results the first irreversible inhibitor of the series toward the yeast enzyme.
