通过分子间基质添加到化物实现了汇总合成
Haruka Fujino1, Takumi Fukuda1, Masanori Nagatomo1
1Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Journal of the American Chemical Society
|July 7, 2020
概括
研究人员用一种新的激素合反应合成了复杂的核酸抗生素Hikizimycin. 这种高效的17步合成为创造有价值的生物活性天然产品提供了新的策略.
科学领域:
- 有机化学
- 医学化学
- 合成化学
背景情况:
- 希基西米辛 (1) 是一种强效的甲虫核酸抗生素.
- 它具有高度功能化的4-氨基-4-脱氧核和10个立体中心.
- 它的复杂结构对整体合成构成重大挑战.
研究的目的:
- 为了实现Hikizimycin的全新合成 (1).
- 开发和应用一种用于构建核心无链的新型激素合反应.
- 建立一个高效的合成路线, 尽量减少功能组的操作.
主要方法:
- 使用四种已知成分的融合合成:葡萄糖衍生物 (4),细胞素 (5),d-曼诺斯 (9) 和d-银酸衍生物 (10).
- 在化和α-alkoxyacyl化物之间开发了一种新型的基结反应.
- 使用Et3B和O2进行激素生成和分子间添加,然后进行选择性糖化和脱保护.
主要成果:
- 在17个步骤中从d- galactose衍生物 (10) 中成功合成Hikizimycin.
- 这种新的激素合策略有效地安装了无核的C5和C6立体中心.
- 在复杂分子合成中证明分子间激素添加的多功能性.
结论:
- 开发的合成策略提供了有效的Hikizimycin途径.
- 这项工作展示了复杂核酸抗生素的全合成方法.
- 该方法有可能合成其他生物活性天然产品.
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