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

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Lipids

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.

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Abbreviations

ASIS:

Aromatic solvent-induced shift

LIS:

Lanthanide-induced shift

NMR:

Nuclear magnetic resonance

HMQC:

Heteronuclear multiple quantum coherence

HMBC:

Heteronuclear multiple bond correlation

DEPT:

Distortionless enhancement by polarization transfer

HR:

High resolution

ESI:

Electrospray ionization

MS:

Mass spectrometry

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Acknowledgments

This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Sciences and Technology of Japan (to T.I., 24550107) for 2012–2014 and for the Strategic Research Base Development Program for Private Universities subsidized MEXT 2009 (S0901022) for 2009–2013.

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Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba, 278-8510, Japan

    Shoujiro Ogawa & Tatsuya Higashi

  2. Department of Chemistry, College of Humanities and Sciences, Nihon University, Sakurajousui, Setagaya, Tokyo, 156-8550, Japan

    Hiroaki Kawamoto, Takashi Mitsuma, Hiroki Fujimori & Takashi Iida

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  1. Shoujiro Ogawa
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  2. Hiroaki Kawamoto
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  3. Takashi Mitsuma
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  4. Hiroki Fujimori
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  5. Tatsuya Higashi
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  6. Takashi Iida
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Correspondence to Takashi Iida.

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Ogawa, S., Kawamoto, H., Mitsuma, T. et al. Stereoselective Synthesis and NMR Characterization of C-24 Epimeric Pairs of 24-Alkyl Oxysterols. Lipids 48, 197–207 (2013). https://doi.org/10.1007/s11745-012-3739-1

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  • DOI: https://doi.org/10.1007/s11745-012-3739-1

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