Revisiting the 7,8-cis-Vitamin D3 derivatives: Synthesis, evaluating the biological activity, and study of the binding configuration

Daisuke Sawada, Shinji Kakuda, Midori Kamimura-Takimoto, Akiko Takeuchi, Yotaro Matsumoto, Atsushi Kittaka

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Four 7,8-cis-1α,25-dihydroxyVitamin D3 derivatives, 7,8-cis- and 7,8-cis-14-epi-1α,25-dihydroxy-19-norVitamin D3 as well as 7,8-cis- and 7,8-cis-14-epi-1α,25-dihydroxyVitamin D3 were synthesized, and their chemical stability was characterized. In our previous work, we disclosed that 14-epi-19-nortachysterol showed the unprecedented binding configuration in human Vitamin D receptor (hVDR), that is, 5,6- and 7,8-s-trans configuration. However, this configuration is variable because of the rotation at the single bond between C7 and C8. For the precise discussion of the 7,8-s-trans configuration, we designed and synthesized the 7,8-cis-locked skeleton of Vitamin D3 derivatives. Among four analogs, the 19-nor derivatives were stable at ambient temperature, and their hVDR binding affinity and co-crystallographic analysis of their hVDR complexes were studied. The other derivatives with the triene system were isomerized to corresponding preVitamin D3 and Vitamin D3.

Original languageEnglish
Pages (from-to)2838-2848
Number of pages11
JournalTetrahedron
Volume72
Issue number22
DOIs
Publication statusPublished - Jun 2 2016

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Calcitriol Receptors
Cholecalciferol
Bioactivity
Calcitriol
Derivatives
Skeleton
Chemical stability
Temperature
previtamin D(3)

Keywords

  • 7,8-cis-Vitamin D
  • Vitamin D receptor
  • Vitamin D
  • X-ray cocrystallography

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Cite this

Revisiting the 7,8-cis-Vitamin D3 derivatives : Synthesis, evaluating the biological activity, and study of the binding configuration. / Sawada, Daisuke; Kakuda, Shinji; Kamimura-Takimoto, Midori; Takeuchi, Akiko; Matsumoto, Yotaro; Kittaka, Atsushi.

In: Tetrahedron, Vol. 72, No. 22, 02.06.2016, p. 2838-2848.

Research output: Contribution to journalArticle

Sawada, Daisuke ; Kakuda, Shinji ; Kamimura-Takimoto, Midori ; Takeuchi, Akiko ; Matsumoto, Yotaro ; Kittaka, Atsushi. / Revisiting the 7,8-cis-Vitamin D3 derivatives : Synthesis, evaluating the biological activity, and study of the binding configuration. In: Tetrahedron. 2016 ; Vol. 72, No. 22. pp. 2838-2848.
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