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- Takeuchi Reon
- Graduate School of Science and Technology, Shizuoka University
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- Fujimoto Junko
- Department of Applied Chemistry and Biochemical Engineering, Faculty of Engineering, Shizuoka University
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- Taguchi Yoshinori
- Graduate School of Medical Photonics, Shizuoka University
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- Ide Ryuji
- Course of Applied Chemistry and Biochemical Engineering, Department of Engineering, Graduate School of Integrated Science and Technology, Shizuoka University
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- Kyan Ryuji
- Research Institute of Green Science and Technology, Shizuoka University
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- Sato Kohei
- Graduate School of Science and Technology, Shizuoka University Department of Applied Chemistry and Biochemical Engineering, Faculty of Engineering, Shizuoka University Course of Applied Chemistry and Biochemical Engineering, Department of Engineering, Graduate School of Integrated Science and Technology, Shizuoka University Research Institute of Green Science and Technology, Shizuoka University
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- Mase Nobuyuki
- Graduate School of Science and Technology, Shizuoka University Department of Applied Chemistry and Biochemical Engineering, Faculty of Engineering, Shizuoka University Course of Applied Chemistry and Biochemical Engineering, Department of Engineering, Graduate School of Integrated Science and Technology, Shizuoka University Research Institute of Green Science and Technology, Shizuoka University
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- Yokoyama Masaru
- Pathogen Genomics Center, National Institute of Infectious Diseases
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- Harada Shigeyoshi
- AIDS Research Center, National Institute of Infectious Diseases
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- Narumi Tetsuo
- Graduate School of Science and Technology, Shizuoka University Department of Applied Chemistry and Biochemical Engineering, Faculty of Engineering, Shizuoka University Graduate School of Medical Photonics, Shizuoka University Course of Applied Chemistry and Biochemical Engineering, Department of Engineering, Graduate School of Integrated Science and Technology, Shizuoka University Research Institute of Green Science and Technology, Shizuoka University
抄録
<p>A 12-keto-type oleanolic acid derivative (4) has been identified as a potent anti-human immunodeficiency virus type-1 (HIV-1) compound that demonstrates synergistic effects with several types of HIV-1 neutralizing antibodies. In the present study, we used a common key synthetic intermediate to carry out the late-stage derivatization of an anti-HIV compound based on the chemical structure of a 12-keto-type oleanolic acid derivative. To execute this strategy, we designed a diketo-type oleanolic acid derivative (5) for chemoselective transformation, targeting the carboxy group and the hydroxyl group on the statine unit, as well as the 3-carbonyl group on the oleanolic acid unit, as orthogonal synthetic handles. We carried out four types of chemoselective transformations, leading to identification of the indole-type derivative (16) as a novel potent anti-HIV compound. In addition, further optimization of the β-hydroxyl group on the statine unit provided the R-4-isobutyl γ-amino acid-type derivative (6), which exhibited potent anti-HIV activity comparable to that of 4 but with reduced cytotoxicity.</p>
収録刊行物
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- ＣＨＥＭＩＣＡＬ ＆ ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ ＢＵＬＬＥＴＩＮ
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ＣＨＥＭＩＣＡＬ ＆ ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ ＢＵＬＬＥＴＩＮ 72 (3), 330-335, 2024-03-25
公益社団法人 日本薬学会