A facile and practical method for the synthesis of trans-(±)-taxifolin and its derivatives via Darzens reaction.

Abstract

The synthesis of racemic trans-taxifolin (trans-(±)-taxifolin) and its derivatives and subsequent chiral separation is the most prevalent chemical method to obtain enantiomerically pure taxifolin and its derivatives. The development of an economical and practical synthetic route to trans-(±)-taxifolin, a key precursor to the enantiomerically pure trans-taxifolin, is therefore of great importance and significance. In this work, we developed a new synthetic method for trans-(±)-taxifolin and its derivatives with 2,4,6-trihydroxyacetophenone as a starting material undergoing hydroxy protection, α-bromination, construction of α,β-epoxy carbonyl products via the Darzens reaction, acid-mediated deprotection, and cyclization to afford the target compounds. This method is highlighted by satisfactory overall yields (20-41%) and proceeds without the use of explosive peroxides (such as H₂O₂), which are commonly employed in methods reported earlier. The avoidance of explosive peroxides in the present method enables safe operation, easy scale-up, and also the synthesis of taxifolin derivatives with oxidant-sensitive groups, largely expanding the substituent scope compared with the previous method.