Total Synthesis and Antibacterial Investigations of 1-Hydroxyboivinianin A

Synthetic investigations of natural products has been instrumental in the development of novel antibacterial small molecules. 1-hydroxyboivinianin A, a lactone containing phenolic bisabolane isolated from marine sediment, has reported antibacterial activity against the aquatic pathogen Vibrio harveyi. The total synthesis of 1-hydroxyboivinianin A and its enantiomer was completed in a six-step sequence in 42 % overall yield. The synthesis leveraged a key diastereoselective nucleophilic addition with chiral imidazolidinone to establish the benzylic tertiary alcohol and intramolecular Horner-Wadsworth Emmons to furnish the lactone. Both enantiomers were found to have negligible antibacterial activity against a panel of gram-positive and negative bacteria and minimal antifungal activity against phytopathogens. Investigations of a possible in vitro lactone hydrolysis to produce an inactive linear acid led to the discovery of a spontaneous cyclization, suggesting the lactone is resistant to hydrolysis and the lactone is not degrading to produce an inactive species.

Automated summary

Synthetic investigations of natural products have played an important role in developing novel antibacterial small molecules. The total synthesis of 1-hydroxyboivinianin A and its enantiomer with a six-step sequence yielded 42% overall. Both enantiomers showed negligible antibacterial activity against a panel of gram-positive and negative bacteria, as well as minimal antifungal activity against phytopathogens.