Synthesis of Sulfur-Containing Analogues of Hedychenone, a Labdane Diterpenoid from <i>Hedychium spicatum</i>

The labdane diterpene hedychenone, isolated from Hedychium spicatum, is an example of a furan-containing natural product. Herein, a new and efficient method for the synthesis of 19 new thio analogues of hedychenone is reported. The present methodology exhibits a broad substrate scope with good to excellent yields without metal or base under mild reaction conditions. The natural compound 1 and four semisynthetic derivatives (3a, 3b, 3i, and 3j) exhibited strong α-glucosidase inhibition activity with IC50 values of 15.93 ± 0.29, 9.70 ± 0.33, 11.82 ± 0.06, 12.23 ± 0.33, and 12.15 ± 0.14 μg/mL, respectively. In addition, compound 3e (6.0 ± 0.04 mm; zone of inhibition) displayed antibacterial activity against Staphylococcus aureus. This study increases the chemical diversity of bioactive hedychenone derivatives and provides a direction for the development of antidiabetic agents.