Design and synthesis of novel derivatives of 6β-hydroxy betunolic acid as antibacterial agents.

6β-Hydroxy betunolic acid (1), has been identified as a novel, effective natural antibiotic lead compound, and hence, thirteen semisynthetic derivatives of 1 were synthesized including twelve novel compounds. Their structure-activity relationship was evaluated against sixteen pathogenic bacterial strains. Results revealed that the presence of a carboxylic acid group at C17 and unsaturation at C20–C29 are essential for the antibacterial activity of 6β-Hydroxy betunolic acid. Further, increased antibacterial activity was observed for 6β-hydroxy betunolic acid with acetyl modification at C3 against S. aureus and MRSA 114, however, none of the analogues including 6β-hydroxy betunolic acid showed antibacterial activity against the Gram-negative bacterial strains tested. [Display omitted] • Thirteen semisynthetic derivatives of 6β-hydroxy betunolic acid were synthesized. • All the derivatives were evaluated for SAR on antibacterial activity. • The C3 acetylated derivative had improved activity against Gram positives. • All the derivatives were inactive towards Gram negative strains. [ABSTRACT FROM AUTHOR]