Design and concise synthesis of novel vitamin D analogues bearing a functionalized aromatic ring on the side chain

Toshie Fujishima; Takuro Komatsu; Yuri Takao; Wataru Yonamine; Tsutomu Suenaga; Hiroaki Isono; Masayuki Morikawa; Keisuke Takaguchi

doi:10.1016/j.tet.2019.01.019

Design and concise synthesis of novel vitamin D analogues bearing a functionalized aromatic ring on the side chain

Toshie Fujishima
, Takuro Komatsu
, Yuri Takao
, Wataru Yonamine
, Tsutomu Suenaga
, Hiroaki Isono
, Masayuki Morikawa
, Keisuke Takaguchi

Tokushima Bunri University

研究成果: ジャーナルへの寄稿 › 記事 › 査読

3 被引用数 (Scopus)

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Five novel vitamin D analogues (2a, 2b, 3a, 3b and 4) bearing an aromatic side chain have been designed and synthesized in a convergent manner. The requisite CD-ring synthons (10a–c) were prepared from C22 aldehyde (5) using four- or five-step procedures. Using turbo-Grignard reagents allowed aromatic side chains with a polar functional moiety to be installed in a single step with excellent yields. A preliminary biological evaluation using bovine thymus vitamin D receptor (VDR) suggested that incorporating a carboxylic acid instead of the C25-hydroxy group had a positive effect on the VDR affinity compared with the corresponding esters.

本文言語	英語
ページ（範囲）	1098-1106
ページ数	9
ジャーナル	Tetrahedron
巻	75
号	8
DOI	https://doi.org/10.1016/j.tet.2019.01.019
出版ステータス	出版済み - 22 2月 2019
外部発表	はい

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title = "Design and concise synthesis of novel vitamin D analogues bearing a functionalized aromatic ring on the side chain",

abstract = "Five novel vitamin D analogues (2a, 2b, 3a, 3b and 4) bearing an aromatic side chain have been designed and synthesized in a convergent manner. The requisite CD-ring synthons (10a{\textendash}c) were prepared from C22 aldehyde (5) using four- or five-step procedures. Using turbo-Grignard reagents allowed aromatic side chains with a polar functional moiety to be installed in a single step with excellent yields. A preliminary biological evaluation using bovine thymus vitamin D receptor (VDR) suggested that incorporating a carboxylic acid instead of the C25-hydroxy group had a positive effect on the VDR affinity compared with the corresponding esters.",

keywords = "Grignard reaction, Lactone, Side-chain analogues, Vitamin D, Vitamin D receptor",

author = "Toshie Fujishima and Takuro Komatsu and Yuri Takao and Wataru Yonamine and Tsutomu Suenaga and Hiroaki Isono and Masayuki Morikawa and Keisuke Takaguchi",

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T1 - Design and concise synthesis of novel vitamin D analogues bearing a functionalized aromatic ring on the side chain

AU - Fujishima, Toshie

AU - Komatsu, Takuro

AU - Takao, Yuri

AU - Yonamine, Wataru

AU - Suenaga, Tsutomu

AU - Isono, Hiroaki

AU - Morikawa, Masayuki

AU - Takaguchi, Keisuke

PY - 2019/2/22

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N2 - Five novel vitamin D analogues (2a, 2b, 3a, 3b and 4) bearing an aromatic side chain have been designed and synthesized in a convergent manner. The requisite CD-ring synthons (10a–c) were prepared from C22 aldehyde (5) using four- or five-step procedures. Using turbo-Grignard reagents allowed aromatic side chains with a polar functional moiety to be installed in a single step with excellent yields. A preliminary biological evaluation using bovine thymus vitamin D receptor (VDR) suggested that incorporating a carboxylic acid instead of the C25-hydroxy group had a positive effect on the VDR affinity compared with the corresponding esters.

AB - Five novel vitamin D analogues (2a, 2b, 3a, 3b and 4) bearing an aromatic side chain have been designed and synthesized in a convergent manner. The requisite CD-ring synthons (10a–c) were prepared from C22 aldehyde (5) using four- or five-step procedures. Using turbo-Grignard reagents allowed aromatic side chains with a polar functional moiety to be installed in a single step with excellent yields. A preliminary biological evaluation using bovine thymus vitamin D receptor (VDR) suggested that incorporating a carboxylic acid instead of the C25-hydroxy group had a positive effect on the VDR affinity compared with the corresponding esters.

KW - Grignard reaction

KW - Lactone

KW - Side-chain analogues

KW - Vitamin D

KW - Vitamin D receptor

UR - https://www.scopus.com/pages/publications/85059866251

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DO - 10.1016/j.tet.2019.01.019

M3 - 記事

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SN - 0040-4020

VL - 75

SP - 1098

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JO - Tetrahedron

JF - Tetrahedron

IS - 8

ER -

Design and concise synthesis of novel vitamin D analogues bearing a functionalized aromatic ring on the side chain

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