Synthesis of [14α-methyl-3H]-24,25-dihydrolanosterol†

We describe, herein, the first synthesis of isomerically pure title compound (6) at high specific activity. This required the development of a convenient, regiospecific synthesis of the Δ8(9)-15-ketone (15) and subsequent alkylation with methyl-[3H3] iodide. A key step in our procedure was the use of an electrochemical reduction of the intermediate [14α-methyl-3H]- 15-oxo -dihydrolanosterol (19). This process was effected cleanly and in high yield to give (6), an important assay tool in the search for cholesterol lowering agents. This approach was found to be significantly superior to the Wolff-Kishner reduction of the corresponding 3-benzoate (18).