Total Syntheses and Preliminary Biological Evaluation of Brominated Fascaplysin and Reticulatine Alkaloids and Their Analogues
Maxim E. Zhidkov,
Polina A. Smirnova,
Oleg A. Tryapkin,
Alexey V. Kantemirov,
Yuliya V. Khudyakova,
Olesya S. Malyarenko,
Svetlana P. Ermakova,
Valeria P. Grigorchuk,
Moritz Kaune,
Gunhild von Amsberg,
Sergey A. Dyshlovoy
Affiliations
Maxim E. Zhidkov
Department of Organic Chemistry and Laboratory of Biologically Active Compounds, School of Natural Sciences, Far Eastern Federal University, 8 Sukhanov Str., Vladivostok 690950, Russia
Polina A. Smirnova
Department of Organic Chemistry and Laboratory of Biologically Active Compounds, School of Natural Sciences, Far Eastern Federal University, 8 Sukhanov Str., Vladivostok 690950, Russia
Oleg A. Tryapkin
Department of Organic Chemistry and Laboratory of Biologically Active Compounds, School of Natural Sciences, Far Eastern Federal University, 8 Sukhanov Str., Vladivostok 690950, Russia
Alexey V. Kantemirov
Department of Organic Chemistry and Laboratory of Biologically Active Compounds, School of Natural Sciences, Far Eastern Federal University, 8 Sukhanov Str., Vladivostok 690950, Russia
Yuliya V. Khudyakova
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, 159 Prospekt 100 Let Vladivostoku, Vladivostok 690022, Russia
Olesya S. Malyarenko
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, 159 Prospekt 100 Let Vladivostoku, Vladivostok 690022, Russia
Svetlana P. Ermakova
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, 159 Prospekt 100 Let Vladivostoku, Vladivostok 690022, Russia
Valeria P. Grigorchuk
Federal Scientific Center of the East Asia Terrestrial Biodiversity (Institute of Biology and Soil Science), Far Eastern Branch of the Russian Academy of Sciences, 159 Prospect 100-Let Vladivostoku, Vladivostok 690022, Russia
Moritz Kaune
Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Gunhild von Amsberg
Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Sergey A. Dyshlovoy
Department of Organic Chemistry and Laboratory of Biologically Active Compounds, School of Natural Sciences, Far Eastern Federal University, 8 Sukhanov Str., Vladivostok 690950, Russia
A simple approach toward the synthesis of the marine sponge derived pigment fascaplysin was used to obtain the marine alkaloids 3-bromofascaplysin and 3,10-dibromofascaplysin. These compounds were used for first syntheses of the alkaloids 14-bromoreticulatate and 14-bromoreticulatine. Preliminary bioassays showed that 14-bromoreticulatine has a selective antibiotic (to Pseudomonas aeruginosa) activity and reveals cytotoxicity toward human melanoma, colon, and prostate cancer cells. 3,10-Dibromofascaplysin was able to target metabolic activity of the prostate cancer cells, without disrupting cell membrane’s integrity and had a wide therapeutic window amongst the fascaplysin alkaloids.
