Synthesis and Antiviral Activities of Neoechinulin B and Its Derivatives

Kota Nishiuchi, Hirofumi Ohashi, Kazane Nishioka, Masako Yamasaki, Masateru Furuta, Takumi Mashiko, Shusuke Tomoshige, Kenji Ohgane, Shinji Kamisuki, Koichi Watashi, Kouji Kuramochi

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


We have previously reported that neoechinulin B (1a), a prenylated indole diketopiperazine alkaloid, shows antiviral activities against hepatitis C virus (HCV) via the inactivation of the liver X receptors (LXRs) and the resultant disruption of double-membrane vesicles. In this study, a two-step synthesis of the diketopiperazine scaffold of 1a was achieved by the base-induced coupling of 1,4-diacetyl-3-{[(tert-butyldimethylsilyl)oxy]methyl}piperazine-2,5-dione with aldehydes, followed by the treatment of the resultant coupling products with tetra-n-butylammonium fluoride. Compound 1a and its 16 derivatives 1b–q were prepared using this method. Furthermore, variecolorin H, a related alkaloid, was obtained by the acid treatment of 1a in MeOH. The antiviral evaluation of 1a and its derivatives revealed that 1a, 1c, 1d, 1h, 1j, 1l, and 1o exhibited both anti-HCV and anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activities. The results of this study indicate that the exomethylene moiety on the diketopiperazine ring is important for the antiviral activities. The antiviral compounds can inhibit the production of HCV and SARS-CoV-2 by inactivating LXRs.

Original languageEnglish
Pages (from-to)284-291
Number of pages8
JournalJournal of Natural Products
Issue number1
Publication statusPublished - 2022 Jan 28
Externally publishedYes

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry


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