Synthesis of 2α- and 2β-(3-hydroxypropyl)- 7,8-cis-14-epi-1α,25-dihydroxy-19-norvitamin D3 and their biological activity

Daisuke Sawada, Eiji Ochiai, Akiko Takeuchi, Shinji Kakuda, Midori Kamimura-Takimoto, Fumihiro Kawagoe, Atsushi Kittaka

Research output: Contribution to journal › Article

1 Citation (Scopus)

Abstract

According to the binding mode of 14-epi-1α,25-dihydroxy-19-nortachysterol in the ligand binding domain of human vitamin D receptor (hVDR), i.e., 5,6- and 7,8-s-trans configuration that was shown by X-ray co-crystallographic analysis, 7,8-cis-locked 1α,25(OH)2D3 analogs were synthesized. In this paper, the synthesis and biological activity of 2α- and 2β-(3-hydroxypropyl)-7,8-cis-14-epi-1α,25-dihydroxy-19-norvitamin D3 are reported. The A-ring and CD-ring precursors for the Julia-Kociensky coupling reaction to create a diene system of the target molecules were prepared using our original methods. hVDR binding affinity and osteocalcin promoter transactivation activity of the new 7,8-cis-14-epi-vitamin D3 analogs were evaluated. Interestingly, the 2β-substituted 7,8-cis-analog was a better binder for hVDR than the 2α-isomeric counterpart.

Original languageEnglish
JournalJournal of Steroid Biochemistry and Molecular Biology
DOIs
Publication statusAccepted/In press - May 24 2016

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Calcitriol Receptors
Bioactivity
Ergocalciferols
Cholecalciferol
Osteocalcin
Transcriptional Activation
Binders
X-Rays
Ligands
X rays
Molecules
1,25-dihydroxy-19-norvitamin D3

Keywords

  • 7,8-cis-19-norvitamin D analog
  • Synthesis
  • Transactivation
  • VDR binding affinity
  • Vitamin D receptor

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Synthesis of 2α- and 2β-(3-hydroxypropyl)- 7,8-cis-14-epi-1α,25-dihydroxy-19-norvitamin D3 and their biological activity. / Sawada, Daisuke; Ochiai, Eiji; Takeuchi, Akiko; Kakuda, Shinji; Kamimura-Takimoto, Midori; Kawagoe, Fumihiro; Kittaka, Atsushi.

In: Journal of Steroid Biochemistry and Molecular Biology, 24.05.2016.

Research output: Contribution to journal › Article

Sawada, D, Ochiai, E, Takeuchi, A, Kakuda, S, Kamimura-Takimoto, M, Kawagoe, F & Kittaka, A 2016, 'Synthesis of 2α- and 2β-(3-hydroxypropyl)- 7,8-cis-14-epi-1α,25-dihydroxy-19-norvitamin D3 and their biological activity', Journal of Steroid Biochemistry and Molecular Biology. https://doi.org/10.1016/j.jsbmb.2016.09.007
Sawada D, Ochiai E, Takeuchi A, Kakuda S, Kamimura-Takimoto M, Kawagoe F et al. Synthesis of 2α- and 2β-(3-hydroxypropyl)- 7,8-cis-14-epi-1α,25-dihydroxy-19-norvitamin D3 and their biological activity. Journal of Steroid Biochemistry and Molecular Biology. 2016 May 24. https://doi.org/10.1016/j.jsbmb.2016.09.007
Sawada, Daisuke ; Ochiai, Eiji ; Takeuchi, Akiko ; Kakuda, Shinji ; Kamimura-Takimoto, Midori ; Kawagoe, Fumihiro ; Kittaka, Atsushi. / Synthesis of 2α- and 2β-(3-hydroxypropyl)- 7,8-cis-14-epi-1α,25-dihydroxy-19-norvitamin D3 and their biological activity. In: Journal of Steroid Biochemistry and Molecular Biology. 2016.
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AU - Ochiai, Eiji

AU - Takeuchi, Akiko

AU - Kakuda, Shinji

AU - Kamimura-Takimoto, Midori

AU - Kawagoe, Fumihiro

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