Synthesis of 2β-substituted-14-epi-previtamin D3 and testing of its genomic activity

Daisuke Sawada; Yuya Tsukuda; Hiroshi Saito; Ken ichiro Takagi; Eiji Ochiai; Seiichi Ishizuka; Kazuya Takenouchi; Atsushi Kittaka

doi:10.1016/j.jsbmb.2010.02.035

Synthesis of 2β-substituted-14-epi-previtamin D₃ and testing of its genomic activity

Daisuke Sawada, Yuya Tsukuda, Hiroshi Saito, Ken ichiro Takagi, Eiji Ochiai, Seiichi Ishizuka, Kazuya Takenouchi, Atsushi Kittaka

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

Abstract

2β-Substituted analogs of 14-epi-previtamin D₃ were synthesized for the first time by the thermal isomerization of the corresponding 14-epi-vitamin D₃ that were available using coupling reaction between the A-ring phosphine oxide derived from a chiral epoxide and CD-ring cis-hydrindanone. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were evaluated, and the new analogs were found to be less active, 0.01-0.18% of VDR binding affinity compared with the natural hormone and EC₅₀ 1.0-9.1nM for transactivation activity, than 14-epi-previtamin D₃ with 0.5% (VDR) and EC₅₀ 0.46nM, respectively.

Original language	English
Pages (from-to)	20-24
Number of pages	5
Journal	Journal of Steroid Biochemistry and Molecular Biology
Volume	121
Issue number	1-2
DOIs	https://doi.org/10.1016/j.jsbmb.2010.02.035
Publication status	Published - Jul 2010
Externally published	Yes

Keywords

14-epi-Previtamin D
Osteocalcin
Vitamin D
Vitamin D receptor

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Biochemistry
Molecular Medicine
Molecular Biology
Endocrinology
Clinical Biochemistry
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.jsbmb.2010.02.035

Cite this

@article{464fb997c7ff45e798a55dcb0ae06159,

title = "Synthesis of 2β-substituted-14-epi-previtamin D3 and testing of its genomic activity",

abstract = "2β-Substituted analogs of 14-epi-previtamin D3 were synthesized for the first time by the thermal isomerization of the corresponding 14-epi-vitamin D3 that were available using coupling reaction between the A-ring phosphine oxide derived from a chiral epoxide and CD-ring cis-hydrindanone. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were evaluated, and the new analogs were found to be less active, 0.01-0.18% of VDR binding affinity compared with the natural hormone and EC50 1.0-9.1nM for transactivation activity, than 14-epi-previtamin D3 with 0.5% (VDR) and EC50 0.46nM, respectively.",

keywords = "14-epi-Previtamin D, Osteocalcin, Vitamin D, Vitamin D receptor",

author = "Daisuke Sawada and Yuya Tsukuda and Hiroshi Saito and Takagi, {Ken ichiro} and Eiji Ochiai and Seiichi Ishizuka and Kazuya Takenouchi and Atsushi Kittaka",

note = "Funding Information: We are grateful to Ms. Junko Shimode and Ms. Ayako Kawaji (Teikyo University) for the spectroscopic measurements. This work was supported in part by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology, Japan (to D.S.) and by a Grant-in-Aid from the Japan Society for the Promotion of Science (to A.K.). ",

year = "2010",

month = jul,

doi = "10.1016/j.jsbmb.2010.02.035",

language = "English",

volume = "121",

pages = "20--24",

journal = "Journal of Steroid Biochemistry and Molecular Biology",

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T1 - Synthesis of 2β-substituted-14-epi-previtamin D3 and testing of its genomic activity

AU - Sawada, Daisuke

AU - Tsukuda, Yuya

AU - Saito, Hiroshi

AU - Takagi, Ken ichiro

AU - Ochiai, Eiji

AU - Ishizuka, Seiichi

AU - Takenouchi, Kazuya

AU - Kittaka, Atsushi

N1 - Funding Information: We are grateful to Ms. Junko Shimode and Ms. Ayako Kawaji (Teikyo University) for the spectroscopic measurements. This work was supported in part by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology, Japan (to D.S.) and by a Grant-in-Aid from the Japan Society for the Promotion of Science (to A.K.).

PY - 2010/7

Y1 - 2010/7

N2 - 2β-Substituted analogs of 14-epi-previtamin D3 were synthesized for the first time by the thermal isomerization of the corresponding 14-epi-vitamin D3 that were available using coupling reaction between the A-ring phosphine oxide derived from a chiral epoxide and CD-ring cis-hydrindanone. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were evaluated, and the new analogs were found to be less active, 0.01-0.18% of VDR binding affinity compared with the natural hormone and EC50 1.0-9.1nM for transactivation activity, than 14-epi-previtamin D3 with 0.5% (VDR) and EC50 0.46nM, respectively.

AB - 2β-Substituted analogs of 14-epi-previtamin D3 were synthesized for the first time by the thermal isomerization of the corresponding 14-epi-vitamin D3 that were available using coupling reaction between the A-ring phosphine oxide derived from a chiral epoxide and CD-ring cis-hydrindanone. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were evaluated, and the new analogs were found to be less active, 0.01-0.18% of VDR binding affinity compared with the natural hormone and EC50 1.0-9.1nM for transactivation activity, than 14-epi-previtamin D3 with 0.5% (VDR) and EC50 0.46nM, respectively.

KW - 14-epi-Previtamin D

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KW - Vitamin D

KW - Vitamin D receptor

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