Total Synthesis and Antibacterial Investigations of 1-Hydroxyboivinianin A.

Abstract

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.