Synthesis of 2α-and 2β-substituted-14-epi-previtamin D 3 and their genomic activity

Daisuke Sawada; Tomoyuki Katayama; Yuya Tsukuda; Nozomi Saito; Hiroshi Saito; Ken Ichiro Takagi; Eiji Ochiai; Seiichi Ishizuka; Kazuya Takenouchi; Atsushi Kittaka

doi:10.1016/j.tet.2010.05.028

Synthesis of 2α-and 2β-substituted-14-epi-previtamin D ₃ and their genomic activity

Daisuke Sawada, Tomoyuki Katayama, Yuya Tsukuda, Nozomi Saito, Hiroshi Saito, Ken Ichiro Takagi, Eiji Ochiai, Seiichi Ishizuka, Kazuya Takenouchi, Atsushi Kittaka

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

16 Citations (Scopus)

Abstract

2α-and 2α-Substituted analogs of 14-epi-previtamin D3 were synthesized and isolated after thermal isomerization of 14-epi-vitamin D3 triene at 80 °C.The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were tested, and the 2a-methyl-substituted analog was found to have greater genomic activity than 14-epi-previtamin D ₃.We found that modification at the C2 position of the seco-steroidal skeleton afforded interesting effects for biological genomic activity for the pre-vitamin D form as well as the natural vitamin D form.

Original language	English
Pages (from-to)	5407-5423
Number of pages	17
Journal	Tetrahedron
Volume	66
Issue number	29
DOIs	https://doi.org/10.1016/j.tet.2010.05.028
Publication status	Published - Jul 17 2010
Externally published	Yes

Keywords

14-epi-Previtamin D
Osteocalcin
Vitamin D
Vitamin Dreceptor

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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10.1016/j.tet.2010.05.028

Cite this

@article{59000f7c2fd14d71a141a34a04f781cb,

title = "Synthesis of 2α-and 2β-substituted-14-epi-previtamin D 3 and their genomic activity",

abstract = "2α-and 2α-Substituted analogs of 14-epi-previtamin D3 were synthesized and isolated after thermal isomerization of 14-epi-vitamin D3 triene at 80 °C.The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were tested, and the 2a-methyl-substituted analog was found to have greater genomic activity than 14-epi-previtamin D 3.We found that modification at the C2 position of the seco-steroidal skeleton afforded interesting effects for biological genomic activity for the pre-vitamin D form as well as the natural vitamin D form.",

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

author = "Daisuke Sawada and Tomoyuki Katayama and Yuya Tsukuda and Nozomi Saito 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 Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology, Japan (to D.S and N.S.) and by a Grant-in-Aid from the Japan Society for the Promotion of Science (to A.K.). ",

year = "2010",

month = jul,

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doi = "10.1016/j.tet.2010.05.028",

language = "English",

volume = "66",

pages = "5407--5423",

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T1 - Synthesis of 2α-and 2β-substituted-14-epi-previtamin D 3 and their genomic activity

AU - Sawada, Daisuke

AU - Katayama, Tomoyuki

AU - Tsukuda, Yuya

AU - Saito, Nozomi

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 Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology, Japan (to D.S and N.S.) and by a Grant-in-Aid from the Japan Society for the Promotion of Science (to A.K.).

PY - 2010/7/17

Y1 - 2010/7/17

N2 - 2α-and 2α-Substituted analogs of 14-epi-previtamin D3 were synthesized and isolated after thermal isomerization of 14-epi-vitamin D3 triene at 80 °C.The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were tested, and the 2a-methyl-substituted analog was found to have greater genomic activity than 14-epi-previtamin D 3.We found that modification at the C2 position of the seco-steroidal skeleton afforded interesting effects for biological genomic activity for the pre-vitamin D form as well as the natural vitamin D form.

AB - 2α-and 2α-Substituted analogs of 14-epi-previtamin D3 were synthesized and isolated after thermal isomerization of 14-epi-vitamin D3 triene at 80 °C.The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were tested, and the 2a-methyl-substituted analog was found to have greater genomic activity than 14-epi-previtamin D 3.We found that modification at the C2 position of the seco-steroidal skeleton afforded interesting effects for biological genomic activity for the pre-vitamin D form as well as the natural vitamin D form.

KW - 14-epi-Previtamin D

KW - Osteocalcin

KW - Vitamin D

KW - Vitamin Dreceptor

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