Optimised conditions for the synthesis of 17O and 18O labelled cholesterol

Abstract

Conditions are described for the preparation of cholesterol with (17)O and (18)O labels from i-cholesteryl methyl ether using minimal amounts of isotopically enriched water. Optimum yields employed trifluoromethanesulfonic acid as catalyst in 1,4-dioxane at room temperature with 5 equivalents of water. An isotopic enrichment >90% of that of the water used for the reaction could be attained. Tetrafluoroboric acid could also be used as catalyst, at the expense of a lower overall reaction yield. Byproducts from the reaction included dicholesteryl ether, methyl cholesteryl ether, compounds formed by ether hydrolysis, and olefins arising from elimination reactions. Reactions in tetrahydrofuran yielded significant amounts of cholesteryl ethers formed by reaction with alcohols arising from hydrolysis of the solvent.

17O NMR spectroscopy as a tool to study hydrogen bonding of cholesterol in lipid bilayers

“…6,9,10 cholesterol ( 17 O natural abundance = 0.0373%), and the practicalities of measuring quadrupolar NMR. In this work 17 O enriched cholesterol was synthesised using previously published conditions, 26 and utilised in solid state 17 O NMR spectroscopy studies of hydrogen bonding. This exploits the single oxygen site on the cholesterol to provide information about hydrogen bonding.…”