title: 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.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
authors.forename: Shoujiro
authors.initials: S
authors.lastname: Ogawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kawamoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Mitsuma
authors.forename: Hiroki
authors.initials: H
authors.lastname: Fujimori
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Higashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Iida
mesh_terms: D000478:Alkylation; D002384:Catalysis; D006900:Hydroxylation; D009682:Magnetic Resonance Spectroscopy; D010087:Oxides / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry; D012428:Ruthenium / Q000737:chemistry; D013237:Stereoisomerism; D013261:Sterols / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: C512313:2,6-dichloropyridine N-oxide; D010087:Oxides; D011725:Pyridines; D013261:Sterols; D012428:Ruthenium