Efficient Synthesis of Phosphorus/Nitrogen-Containing Chrysin Derivatives via Classic Reactions

Chrysin is a widely distributed natural flavonoid with broad biological activities, but its poor bioavailability and insufficient efficacy limit its clinical applications. Based on prodrug and combination principles, we designed and synthesized sixteen new chrysin derivatives containing phosphonate, phosphoramidate and primary amine groups with different spaces at C-7 position of chrysin in 66-93 % yields. The synthetic strategies involve the use of classic Arbuzov, Staudinger-phosphite and Staudinger-reduction reactions. The derivatives were herein prepared from easily available starting materials under mild conditions and fully characterized by H-1/C-13/P-31 NMR, IR, MS, elemental analysis or HRMS.