Despite the novelty of bacterial farnesylated DMB biosynthesis, several synthetic approaches have already investigated benzimidazoles featuring various substituent patterns. They were found to exhibit a broad range of pharmacological activities from antimicrobial and anticancer to anthelmintic, insecticidal and antiinflammatory activities, which raised our interest in assessing the pharmacological activities of the sandacrabins as well. The isolated yields of sandacrabin B and C were comparably low, so we first aimed for a total synthesis of sandacrabin B and C (see Figure ) by adapting the synthesis route from the general experimental procedures for the synthesis of benzimidazoliums described by Lim et al.. Decrease in temperature, while changing the deprotonating agent from K2CO3 to NaH during the SN-type reaction also allowed us to obtain mono-farnesylated versions called sandacrabin D and E in quantitative yields. Sandacrabin D and E were used to study the influence of the second farnesylation on the biological activities of the sandacrabins (see Figure ). It is worth mentioning that we detect only trace amounts of those derivatives in the extracts of MSr10575 (see SI), showing that sandacrabin biosynthesis is highly optimized for generating bis-farnesylated sandacrabins. Inspired by the diverse activities described for other benzimidazoles, we tested the sandacrabins activity against a broad panel of test organisms. Minimal inhibitory concentrations (MICs) for sandacrabin A-E were determined against a panel of Gram-positive, Gramnegative, as well as fungal human pathogens (see Table ). Antiviral activity was assessed for the human pathogenic corona virus HCoV229E. Huh-7.5 cells constitutively expressing a firefly luciferase reporter gene were therefore infected by a renilla luciferase HCoV229E reporter virus in the presence of indicated concentrations of the compound for 48h at 33 °C. After lysis of cells, the renilla-firefly luciferase dual assay allows assessment of reduction changes in viral replication, while monitoring the cell viability in parallel. Insecticidal activity was determined by applying 0.5 µL of an acetonic sandacrabin dilution to the posterior segment of adult Acyrthosiphon pisum adapted from the procedure described by Ahumada et al. After assessing the minimal insecticidal concentration in a small test group of three insects in a dilution series from 5-0.05 µg sandacrabin applied per insect, the death rate of 20 insects at this concentration was evaluated (see Table ).