ジヒドロレチノイン酸類の合成と生物活性

和田 昭盛; 松田 一朗; 小山 智大; 佐藤 陽; 岡野 登志夫; 中川 公恵

doi:10.20632/vso.98.3_97

Synthesis and biological evaluation of dihydroretinoic acids

Akimori Wada, Ichiro Matsuda, Tomohiro Koyama, Hinata Satou, Toshio Okano, Kimie Nakagawa

Author information

Akimori Wada [Japan]
Laboratory of Organic Chemistry for Life Science, Kobe Pharmaceutical University, 4-19-1, Motoyamakita-machi, Higashinada, Kobe 658-8558, Japan [Japan]
Ichiro Matsuda [Japan]
Laboratory of Organic Chemistry for Life Science, Kobe Pharmaceutical University, 4-19-1, Motoyamakita-machi, Higashinada, Kobe 658-8558, Japan [Japan]
Tomohiro Koyama [Japan]
Laboratory of Organic Chemistry for Life Science, Kobe Pharmaceutical University, 4-19-1, Motoyamakita-machi, Higashinada, Kobe 658-8558, Japan [Japan]
Hinata Satou [Japan]
Laboratory of Organic Chemistry for Life Science, Kobe Pharmaceutical University, 4-19-1, Motoyamakita-machi, Higashinada, Kobe 658-8558, Japan [Japan]
Toshio Okano [Japan]
Laboratory of Hygienic Science, Kobe Pharmaceutical University, 4-19-1, Motoyamakita-machi, Higashinada, Kobe 658-8558, Japan [Japan]
Kimie Nakagawa [Japan]
Laboratory of Hygienic Sciences, The Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Port Island Campus 1-1-3, Minatojima, Chuo-ku, Kobe 650-8586 Japan [Japan]

Keywords: dihydroretinoic acid, conjugate addition, structure-activity relationship, nuclear receptor, transcriptional activity

JOURNAL OPEN ACCESS

2024 Volume 98 Issue 3 Pages 97-107

DOI https://doi.org/10.20632/vso.98.3_97

Details

Abstract

Various ethyl dihydroretionates were prepared by the conjugate reduction of β-ionylidenacetaldehydes and C-18 ketones using ethyldimethylsilyl hydride and subsequent Emmons-Horner reaction with C5- or C2-phosphonate. These esters were hydrolyzed to afford the corresponding dihydroretinoic acids and their biological activities were evaluated. Among the synthesized analogs, 8Z-7,10-dihydroretinoic acid showed higher transcriptional activities for the retinoid X receptor responsive element gene and for the RXRα-GAL4 expression gene than 9Z-retinoic acid (a natural ligand).

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