Synthetic and Biological Studies of Juglorubin and Related Naphthoquinones
Synthetic and Biological Studies of Juglorubin and Related Naphthoquinones
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核桃红素及相关萘醌类化合物的合成与生物学研究
DOI：
10.1021/acs.joc.9b02119
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Kuramochi Kouji
中科院分区：
文献类型：
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作者：
Kamo Shogo;Saito Tatsuo;Kusakabe Yasuha;Tomoshige Shusuke;Uchiyama Masanobu;Tsubaki Kazunori;Kuramochi Kouji
核桃红素、核桃脂素和核桃复合物A/B是从链霉菌分离的天然存在的萘醌二聚体。这些二聚体被认为是从胡桃霉素C（一种从同一种链霉菌中分离出来的单体萘醌）生物遗传学上衍生的。在这项研究中，核桃霉素C衍生物的二聚反应，在这些天然产物的全合成的关键步骤，进行了研究。核桃红素是由二聚反应的次要产物通过形成核桃球蛋白A/B立体异构体而合成的。二聚反应的机制以及一个合理的生物合成途径，以获得核桃霉素C核桃红色素提出。并对五个化合物的抗菌活性和细胞毒活性进行了评价。其中1′-O-甲基胡桃楸素B二甲酯和胡桃霉素C对枯草芽孢杆菌具有抗菌活性。1′-O-甲基胡桃楸素B二甲酯和胡桃霉素C对人结肠癌HCT 116细胞和人白血病HL-60细胞具有细胞毒作用。1′-O-甲基胡桃楸素B二甲酯对人正常MRC-5细胞的细胞毒活性与对人癌细胞的细胞毒活性相当。相比之下，胡桃霉素C对正常MRC-5细胞的毒性较小，表明对癌细胞具有显著的选择性。
Juglorubin, juglorescein, and juglocombins A/B are naturally occurring naphthoquinone dimers isolated fromStreptomycessp. These dimers are proposed to be biogenetically derived from juglomycin C, a monomeric naphthoquinone isolated from the sameStreptomycessp. In this study, the dimerization of a juglomycin C derivative, a key step in the total syntheses of these natural products, was investigated. Juglorubin was synthesized from the minor product of the dimerization via the formation of the juglocombin A/B stereoisomers. A mechanism for the dimerization reaction as well as a plausible biosynthetic pathway to obtain juglorubin from juglomycin C are proposed. Furthermore, the antibacterial and cytotoxic activities of five synthetic compounds were evaluated. Among the compounds tested in this study, 1′-O-methyljuglocombin B dimethyl ester and juglomycin C exhibited antibacterial activity againstBacillus subtilis. 1′-O-Methyljuglocombin B dimethyl ester and juglomycin C showed cytotoxicity against human colon carcinoma HCT116 cells and human leukemia HL-60 cells. 1′-O-Methyljuglocombin B dimethyl ester exhibited cytotoxicity against human normal MRC-5 cells as strong as that against human cancer cells. In contrast, juglomycin C was less toxic against normal MRC-5 cells, indicating a significant selectivity toward cancer cells.