Stereoselective Synthesis and NMR Characterization of C‐24 Epimeric Pairs of 24‐Alkyl Oxysterols

Abstract

Two pairs of C-24 epimeric (24R)-/(24S)-24-hydroxy-24-methyl-5α-cholestan-3β-yl acetates and (24R)-/(24S)-25-hydroxy-24-methyl-5α-cholestan-3β-yl acetates as well as some related 24-ethyl oxysterol analogs were stereoselectively synthesized directly from the respective parent 24-alkyl sterols by a remote O-insertion reaction with 2,6-dichloropyridine N-oxide (DCP) in the presence of a catalytic amount of (5,10,15,20-tetramesitylporphrinate) ruthenium(II) carbonyl complex [Ru(TMP)CO] and HBr. ¹H- and ¹³C-NMR signals serving to differentiate each of the two epimeric pairs were interpreted. The C-24 alkyl oxysterols epimeric at C-24 were found to be effectively characterized by the aromatic solvent-induced shift (ASIS) by C₅D₅N, particularly for the difference in the ¹³C resonances in the substituted cholestane side chain. A method for differentiating the ¹H and ¹³C signal assignment of the terminal 26-/27-CH₃ in the iso-octane side chain was also discussed on the basis of a combined use of the preferred conformational analysis and HMQC and HMBC techniques. The present method may be useful for determining the stereochemical configuration at C-24 of this type of 24-alkyl oxysterols.