Synthesis of Sulfur-Containing Analogues of Hedychenone, a Labdane Diterpenoid from Hedychium spicatum

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 alpha-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 mu g/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.

Automated summary

A new and efficient method for synthesizing thio analogues of hedychenone was reported, and the compounds exhibited strong α-glucosidase inhibition and antibacterial activities. This study provides a new direction for the development of antidiabetic agents.