Paper

• Synthesis and in Vitro Cytotoxicity Evaluation of Jadomycins
  Erika Iwasaki; Yoshimi Shimizu; Yusuke Akagi; Toshiya Komatsu
  Chemical and Pharmaceutical Bulletin, Sep. 2023, [Reviewed]
  Jadomycins, which are benzo[b]phenanthridine-type alkaloids isolated from Streptomyces venezuelae ISP5230, exhibit cytotoxic activity against multidrug-resistant breast cancer cells. We have previously achieved the total synthesis of jadomycins using the direct arylation of juglone as a key step. In this study, we achieved the total synthesis of jadomycin T and jadomycin aglycons using L-threonine and 1-amino-2-propanol as nitrogen sources. Additionally, we evaluated the cytotoxic activity of eight compounds, including glycosides, jadomycin T, and their corresponding aglycons, in eight types of tumor cells. The evaluated jadomycins tended to exhibit stronger cytotoxic activity as aglycons than as glycosides. Although the presence of a 1,3-oxazolidine ring derived from an amino acid was not essential, the presence of the 1,3-oxazolidine ring showed strong activity when the ring had a carboxyl group. Furthermore, compared to the non-natural isomer at a different position on the phenolic hydroxyl group, the naturally occurring phenanthroviridin aglycon exhibited stronger cytotoxic activity. In addition, this study suggests that jadomycins may become lead compounds for the treatment of brain tumors; however, further studies on their ability to penetrate the blood-brain barrier are required.

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• Total synthesis of jadomycins A, B, and l-digitoxosyl-phenanthroviridin
  Yusuke Akagi; Yuta Mori; Yudai Sato; Erika Iwasaki; Toshiya Komatsu
  Tetrahedron Letters, Jul. 2022, [Reviewed]
  We report the total synthesis of jadomycins A, B, and l-digitoxosyl-phenanthroviridin. 2-Aryl-5-hydroxy-1,4-naphthoquinones, which were synthesized utilizing a Pd-catalyzed direct arylation of 5-hydroxy-1,4-naphthoquinone with aryl iodide, were converted into jadomycin A through introduction of l-isoleucine, followed by oxidative cyclization. Mitsunobu reaction of jadomycin A with 3,4-di-O-acetyl-l-digitoxose, which was prepared from commercially available 3,4-di-O-acetyl-6-deoxy-l-glucal, followed by deacetylation, gave jadomycin B. Additionally, the first total synthesis of l-digitoxosyl-phenanthroviridin was successful via Mitsunobu reaction of phenanthroviridin aglycon with 3,4-di-O-acetyl-l-digitoxose.

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