Protecting-Group-Free Total Syntheses of Rubrolide R and S

The two marine natural products rubrolide R (1) and S (2) were synthesised in only three linear steps starting from commercially available tetronic acid without using protecting group chemistry. Key steps in the syntheses were the Pd-catalysed Suzuki-Miyaura cross-coupling followed by a vinylogous aldol condensation. Both compounds have been tested for their antibiotic and antiviral activities. At a concentration of 10 mu M rubrolide R (1) and S (2), a 2-log and 1.5-log reduction in virus titre has been detected for a seasonal influenza virus (H3N2) and the pandemic swine influenza virus (pH1N1), respectively.