Synthesis and antibacterial evaluation of novel hydrophilic ocotillol-type triterpenoid derivatives from 20(S)-protopanaxadiol

Triterpenoid saponins are involved in plant defense systems to inhibit bacterial invasion. A new series of hydrophilic ocotillol-type triterpenoid derivatives 5-26 have been synthesized with antibacterial activity against Gram-positive bacteria, including a community associated methicillin-resistant <i>Staphylococcus aureus</i> (CA-MRSA; strain USA300). From this series, compounds 6 and 15 were found to be the most active, both with MIC values of 2 µg/mL against <i>B. subtilis</i> 168 and 8 µg/mL against <i>S. aureus</i> USA300, respectively. Furthermore, subsequent assays showed that compounds 6 and 15 displayed strong synergistic effects at sub-MIC levels against both <i>S. aureus</i> USA300 and <i>B. subtilis</i> 168 when combined with two commercial antibiotics, kanamycin and chloramphenicol. Preliminary structure-activity relationship studies were also performed.