A Practical and Efficient Approach to the Preparation of Bioactive Natural Product Wogonin

A scalable and practical route to wogonin, a bioactive natural product with multiple pharmacological activities which is currently under phase I/II clinical studies, is described. Wogonin was obtained via a four-step process starting from commercially available chrysin and including the Elbs oxidation, benzylation, methylation, and the final debenzylation. The whole procedure gives the target product in a 38% overall yield with >99% purity. Key steps in this process including oxidation and methylation are discussed in detail. The optimized process has been successfully demonstrated on the kilogram scale to support ongoing clinical development of wogonin.