Optimized one-step preparation of a bioactive natural product, guaiazulene-2,9-dione

We previously isolated a natural product, namely guaiazulene-2,9-dione showing strong antibacterial activity against Vibrio anguillarum , from a gorgonian Muriceides collaris collected in South China Sea. In this experiment, guaiazulene-2,9-dione was quantitatively synthesized with an optimized one-step bromine oxidation method using guaiazulene as the raw material. The key reaction condition including reaction time and temperature, drop rate of bromine, concentration of aqueous THF solution, respective molar ratio of guaiazulene to bromine and acetic acid, and concentration of guaiazulene in aqueous THF solution, were investigated individually at five levels each for optimization. Combined with the verification test to show the absolute yield of each optimization step, the final optimal condition was determined as: when a solution of 0.025 mmol mL −1 guaiazulene in 80% aqueous THF was treated with four volumes of bromine at a drop rate of 0.1 mL min −1 and four volumes of acetic acid at −5°C for three hours, the yield of guaiazulene-2,9-dione was 23.72%. This was the first report concerning optimized one-step synthesis to provide a convenient method for the large preparation of guaiazulene-2,9-dione.