Concise synthesis and biological activities of 2α-alkyl- and 2α-(ω-hydroxyalkyl)-20-epi-1α,25-dihydroxyvitamin D 3

Shinobu Honzawa; Yoshitomo Suhara; Ken Ichi Nihei; Nozomi Saito; Seishi Kishimoto; Toshie Fujishima; Masaaki Kurihara; Takayuki Sugiura; Keizo Waku; Hiroaki Takayama; Atsushi Kittaka

doi:10.1016/S0960-894X(03)00739-X

Concise synthesis and biological activities of 2α-alkyl- and 2α-(ω-hydroxyalkyl)-20-epi-1α,25-dihydroxyvitamin D ₃

Shinobu Honzawa, Yoshitomo Suhara, Ken Ichi Nihei, Nozomi Saito, Seishi Kishimoto, Toshie Fujishima, Masaaki Kurihara, Takayuki Sugiura, Keizo Waku, Hiroaki Takayama, Atsushi Kittaka

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

27 Citations (Scopus)

Abstract

We found a concise route to the Trost A-ring precursor enyne for synthesizing 2α-alkylated 1α,25-dihydroxyvitamin D₃ (1) from D-glucose. The enynes were coupled with the 20-epi-CD ring part to study the effect of the double modification of 2α-substitution and 20-epimerization upon biological activities of 1. The novel three analogues of 2α-alkyl- and four analogues of 2α-(ω -hydroxyalkyl)-20-epi-1α,25-dihydroxyvitamin D₃ (5b-d and 6a-d) showed higher binding affinity for vitamin D receptor (VDR) and more potent activity in induction of HL-60 cell differentiation than those of the natural hormone 1.

Original language	English
Pages (from-to)	3503-3506
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	13
Issue number	20
DOIs	https://doi.org/10.1016/S0960-894X(03)00739-X
Publication status	Published - 2003 Oct 20
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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Honzawa, S., Suhara, Y., Nihei, K. I., Saito, N., Kishimoto, S., Fujishima, T., Kurihara, M., Sugiura, T., Waku, K., Takayama, H., & Kittaka, A. (2003). Concise synthesis and biological activities of 2α-alkyl- and 2α-(ω-hydroxyalkyl)-20-epi-1α,25-dihydroxyvitamin D ₃. Bioorganic and Medicinal Chemistry Letters, 13(20), 3503-3506. https://doi.org/10.1016/S0960-894X(03)00739-X

Honzawa, S, Suhara, Y, Nihei, KI, Saito, N, Kishimoto, S, Fujishima, T, Kurihara, M, Sugiura, T, Waku, K, Takayama, H & Kittaka, A 2003, 'Concise synthesis and biological activities of 2α-alkyl- and 2α-(ω-hydroxyalkyl)-20-epi-1α,25-dihydroxyvitamin D ₃', Bioorganic and Medicinal Chemistry Letters, vol. 13, no. 20, pp. 3503-3506. https://doi.org/10.1016/S0960-894X(03)00739-X

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title = "Concise synthesis and biological activities of 2α-alkyl- and 2α-(ω-hydroxyalkyl)-20-epi-1α,25-dihydroxyvitamin D 3",

abstract = "We found a concise route to the Trost A-ring precursor enyne for synthesizing 2α-alkylated 1α,25-dihydroxyvitamin D3 (1) from D-glucose. The enynes were coupled with the 20-epi-CD ring part to study the effect of the double modification of 2α-substitution and 20-epimerization upon biological activities of 1. The novel three analogues of 2α-alkyl- and four analogues of 2α-(ω -hydroxyalkyl)-20-epi-1α,25-dihydroxyvitamin D3 (5b-d and 6a-d) showed higher binding affinity for vitamin D receptor (VDR) and more potent activity in induction of HL-60 cell differentiation than those of the natural hormone 1.",

author = "Shinobu Honzawa and Yoshitomo Suhara and Nihei, {Ken Ichi} and Nozomi Saito and Seishi Kishimoto and Toshie Fujishima and Masaaki Kurihara and Takayuki Sugiura and Keizo Waku and Hiroaki Takayama and Atsushi Kittaka",

note = "Funding Information: We are grateful to Miss Junko Shimode and Miss Maroka Kitsukawa for the spectroscopic measurements. This work has been supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology, Japan and in part by a grant (MF-16) from the Organization for Pharmaceutical Safety and Research.",

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doi = "10.1016/S0960-894X(03)00739-X",

language = "English",

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T1 - Concise synthesis and biological activities of 2α-alkyl- and 2α-(ω-hydroxyalkyl)-20-epi-1α,25-dihydroxyvitamin D 3

AU - Honzawa, Shinobu

AU - Suhara, Yoshitomo

AU - Nihei, Ken Ichi

AU - Saito, Nozomi

AU - Kishimoto, Seishi

AU - Fujishima, Toshie

AU - Kurihara, Masaaki

AU - Sugiura, Takayuki

AU - Waku, Keizo

AU - Takayama, Hiroaki

AU - Kittaka, Atsushi

N1 - Funding Information: We are grateful to Miss Junko Shimode and Miss Maroka Kitsukawa for the spectroscopic measurements. This work has been supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology, Japan and in part by a grant (MF-16) from the Organization for Pharmaceutical Safety and Research.

PY - 2003/10/20

Y1 - 2003/10/20

N2 - We found a concise route to the Trost A-ring precursor enyne for synthesizing 2α-alkylated 1α,25-dihydroxyvitamin D3 (1) from D-glucose. The enynes were coupled with the 20-epi-CD ring part to study the effect of the double modification of 2α-substitution and 20-epimerization upon biological activities of 1. The novel three analogues of 2α-alkyl- and four analogues of 2α-(ω -hydroxyalkyl)-20-epi-1α,25-dihydroxyvitamin D3 (5b-d and 6a-d) showed higher binding affinity for vitamin D receptor (VDR) and more potent activity in induction of HL-60 cell differentiation than those of the natural hormone 1.

AB - We found a concise route to the Trost A-ring precursor enyne for synthesizing 2α-alkylated 1α,25-dihydroxyvitamin D3 (1) from D-glucose. The enynes were coupled with the 20-epi-CD ring part to study the effect of the double modification of 2α-substitution and 20-epimerization upon biological activities of 1. The novel three analogues of 2α-alkyl- and four analogues of 2α-(ω -hydroxyalkyl)-20-epi-1α,25-dihydroxyvitamin D3 (5b-d and 6a-d) showed higher binding affinity for vitamin D receptor (VDR) and more potent activity in induction of HL-60 cell differentiation than those of the natural hormone 1.

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Concise synthesis and biological activities of 2α-alkyl- and 2α-(ω-hydroxyalkyl)-20-epi-1α,25-dihydroxyvitamin D ₃

Abstract

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