Synthesis of cholesterol analogs having varying length alkyl side chains including cholesterol-23, 23, 24, 24, 25, 26, 26, 26, 27, 27, 27-d11 as probes of cholesterol's functions and properties

•We report a practical synthesis of isoalkyl side-chain analogs of cholesterol bearing a long aliphatic chain.•We describe a short synthesis of cholesterol-d11, which bears deuterium atoms at C23, 23, 24, 24, 25, 26, 26, 26, 27, 27, 27.•Cholesterol-d11 may be a useful probe for coherent anti-Stokes Raman scattering and stimulated Raman scattering microscopy.•Cyano-containing sterols were alkylated with 1 equiv. of alkyl bromides, alkyl tosylates, or alkyl mesylates.•The CCN bond was converted to a CH bond by reductive decyanation with potassium and a crown ether in toluene.

Cholesterol-23, 23, 24, 24, 25, 26, 26, 26, 27, 27, 27-d11 and nondeuterated long-chain analogs of cholesterol were prepared by alkylation of cyano-containing sterols with isopentyl-d11 4-methylbenzenesulfonate (1.0 equiv.) or with isoalkyl bromides, followed by reductive decyanation with excess potassium metal and a crown ether in toluene. The products are potentially useful probes of the role of the side-chain of cholesterol in the sterol's interactions with membrane lipids and proteins.

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