Synthetic and Biological Studies of Juglorubin and Related Naphthoquinones

Shogo Kamo, Tatsuo Saito, Yasuha Kusakabe, Shusuke Tomoshige, Masanobu Uchiyama, Kazunori Tsubaki, Kouji Kuramochi

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Abstract

Juglorubin, juglorescein, and juglocombins A/B are naturally occurring naphthoquinone dimers isolated from Streptomyces sp. These dimers are proposed to be biogenetically derived from juglomycin C, a monomeric naphthoquinone isolated from the same Streptomyces sp. 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 against Bacillus 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.

Original languageEnglish
Pages (from-to)13957-13966
Number of pages10
JournalJournal of Organic Chemistry
Volume84
Issue number21
DOIs
Publication statusPublished - 2019 Nov 1
Externally publishedYes

ASJC Scopus subject areas

  • Organic Chemistry

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    Kamo, S., Saito, T., Kusakabe, Y., Tomoshige, S., Uchiyama, M., Tsubaki, K., & Kuramochi, K. (2019). Synthetic and Biological Studies of Juglorubin and Related Naphthoquinones. Journal of Organic Chemistry, 84(21), 13957-13966. https://doi.org/10.1021/acs.joc.9b02119