Synthesis of (6E)-8-Thia- and (14E)-13-Thia-2,3-oxidosqualene: Inhibitors of 2,3-Oxidosqualene-Lanosterol Cyclase

Article abstract of DOI:10.1021/jo00098a048

Synthesis of (6E)-8-thia-2,3-oxidosqualene (22) and (14E)-13-thia-2,3-oxidosqualene (34) as inhibitors of 2,3-oxidosqualene-lanosterol cyclase are reported.Synthesis of 22 required the stereospecific generation of a vinyl sulfide.This was achieved by a new coupling of a benzenethiosulfonate (15) and a lithiated vinyl iodide (18).Synthesis of 34 involved similar coupling of benzenethiosulfonate 29 with lithium reagent obtained from vinyl iodide 33.The required (E)-vinyl iodides 18 and 33 were prepared by zirconium-catalyzed carboalumination of 4-pentyn-1-ol, (16) and 2,6-dimethyl-2(E),6(E)-dien-10-yne (32) respectively.Both 22 and 34 inhibited 2,3-oxidosqualene-lanosterol cyclase from Candida albicans with IC 50 values of 0.68 and 45 μM, respectively.