从麦拉宁生物合成中间体半合成一种抗癌 DPAGT1 抑制剂。
Semisynthesis of an Anticancer DPAGT1 Inhibitor from a Muraymycin Biosynthetic Intermediate.
机构信息
Department of Pharmaceutical Sciences, College of Pharmacy , University of Tennessee Health Science Center , 881 Madison Avenue , Memphis , Tennessee 38163 , United States.
Laboratory of Microbiology , Institute of Microbial Chemistry (BIKAKEN) , 3-14-23, Kamiosaki , Shinagawa-ku, Tokyo 141-0021 , Japan.
出版信息
Org Lett. 2019 Feb 15;21(4):876-879. doi: 10.1021/acs.orglett.8b03716. Epub 2019 Jan 30.
Abstract
We have explored a method to convert a muraymycin biosynthetic intermediate 3 to an anticancer drug lead 2 for in vivo and thorough preclinical studies. Cu(OAc) forms a stable complex with the amide 4 and prevents electrophilic reactions at the 2-((3-aminopropyl)amino)acetamide moiety. Under the present conditions, the desired 5″-primary amine was selectively protected with (Boc)O to yield 6. The intermediate 6 was converted to 2 in two steps with 90% yield.
摘要
我们探索了一种将默拉霉素生物合成中间体 3 转化为抗癌药物先导化合物 2 的方法，以便进行体内和全面的临床前研究。Cu(OAc)与酰胺 4 形成稳定的配合物，防止 2-((3-氨丙基)氨基)乙酰胺部分的亲电反应。在目前的条件下，用（Boc）O 选择性地保护所需的 5″-伯胺，得到 6。中间体 6 经两步反应以 90%的收率转化为 2。
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