A novel total synthesis of (+)-brazilin

Abstract

Brazilin, structurally composed of a chroman skeleton cis-fused with a 2,3-dihydro-1H-indene unit, is an important active component of the famous traditional Chinese medicine, Caesalpinia sappan L., which belongs to homoisoflavonoid natural products. Brazilin possesses a series of outstanding bioactivities, such as antitumor, anti-inflammatory, hypoglycemic, antibacterial, hepatoprotective activities, which attracts the great interest of synthetic chemists and medicinal chemists. In almost all of the recently published approaches to brazilin, dihydroxylation using highly toxic osmium reagents was employed to construct chiral hydroxyl at C-3 position. Herein, we described a total synthesis of (+)-brazilin from 3,4-dimethoxybenzyl alcohol via overall nine steps, including oxidation using air to prepare hydroxyl at C-3 position, a lipase-catalyzed desymmetrization to establish chiral hydroxyl at the C-3 position, and a trifluoroacetic acid-catalyzed one-pot intramolecular tandem Prins/Friedel-Crafts reaction to construct the cis-fused chromane and indane framework.

Graphical Abstract

Keywords:

• Brazilin
• desymmetrization
• natural products
• total synthesis

Acknowledgments

We thank the National Science Foundation of China (82003810) for the funding support.