Affiliation: | 1. RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan phone: +81 (0)48 467-9373 fax: +81 (0)48 462-4666 Sodeoka Live Cell Chemistry Project, ERATO, Japan Science and Technology Agency, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan;2. RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan phone: +81 (0)48 467-9373 fax: +81 (0)48 462-4666 School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan;3. RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan phone: +81 (0)48 467-9373 fax: +81 (0)48 462-4666 |
Abstract: | Epipolythiodiketopiperazine (ETP) alkaloids are structurally characterized by the presence of diketopiperazine rings having sensitive (poly)sulfide bridges, and most of them are classified as fungal secondary metabolites. Various biological activities have been reported for members of this family, including cytotoxic, antibacterial, antimicrobial, antiviral, antitumor, antiallergic, and antimalarial activities. Notably, some of the molecules were reported to show specific inhibitory activities against certain critical enzymes. Since the supply of these compounds from natural sources is quite limited, efficient chemical syntheses of ETP alkaloids would be useful for biological studies. However, total syntheses of ETP alkaloids remain a formidable challenge in current synthetic organic chemistry because of their structural complexity. In this review article, we present an overview of synthetic approaches to the ETP alkaloids during the past 50 years, and discuss significant milestones. We also summarize the biological activities of these compounds, focusing on the molecular mechanisms. |