Total Synthesis and Antibacterial Investigation of Plusbacin A3
Total Synthesis and Antibacterial Investigation of Plusbacin A3
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Plusbacin A3的全合成及抗菌研究
DOI：
10.1021/acs.orglett.7b01629
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发表时间：
2017
期刊：
影响因子：
5.2
通讯作者：
Ichikawa Satoshi
中科院分区：
文献类型：
--
作者：
Katsuyama Akira;Paudel Atmika;Panthee Suresh;Hamamoto Hiroshi;Kawakami Toru;Hojo Hironobu;Yakushiji Fumika;Ichikawa Satoshi
普鲁斯巴星A3（1）的全合成已使用溶剂依赖性非对映异构体Joullie <$-Ugi三组分反应（JU-3CR）作为关键步骤完成。通过将JU-3CR与可转化的异氰化物策略相结合来构建两个反式-3-羟基-1-脯氨酸残基。随后的肽偶联和大环内酰胺化得到普鲁斯巴星A3。通过与双脱氧类似物的抗菌活性比较，发现β-羟基天冬氨酸残基是1抗菌活性所必需的。值得注意的是，金黄色葡萄球菌对普鲁斯巴星A3产生耐药性的可能性很低。
The total synthesis of plusbacin A3(1) has been accomplished using a solvent-dependent diastereodivergent Joullié–Ugi three-component reaction (JU-3CR) as a key step. Twotrans-3-hydroxy-l-proline residues were constructed by combining the JU-3CR with a convertible isocyanide strategy. Subsequent peptide coupling and macrolactamization afforded plusbacin A3. Investigating the antibacterial activity of1compared with that of its dideoxy analogue revealed that thethreo-β-hydroxyaspartic acid residues are essential for antibacterial activity. Notably, there is a low potential for the development of resistance inS.aureusagainst plusbacin A3.