Synthesis and biological activity of 19-azasqualene 2,3-epoxide as inhibitor of 2,3-oxidosqualene cyclase

Article abstract of DOI:10.1016/0223-5234(93)90026-B

19-Azasqualene 2,3-epoxide and its N-oxide, high-energy intermediate analogue inhibitors of 2,3-oxidosqualene (SO) cyclase were obtained by total synthesis.These compounds were designed to mimic the C-20 carbonium ion precursor of lanosterol formed during SO cyclization.The synthesis involved the preparation of C22squalenoid aldehyde epoxide through a new procedure and the reconstruction of the squalenoid chain bearing a nitrogen at C-19 (pro C-20). 19-Azasqulene 2,3-epoxide was active on SO cyclase from rat and pig liver with an IC50 of 1.5 μM in pig. while in SO cyc lases of yeast (S cerevisiae and C albicans) microsomes it was 20-30-fold less active.It was inactive on squalene epoxidase from rat and pig liver at the highest concentrations tested (100 μM). 2,3-oxidosqualane cyclase inhibitors/ epoxy azasqualanes/ hypocholesterolemic/ antifungals