Synthesis of icariin from kaempferol through regioselective methylation and para-Claisen–Cope rearrangement

• Qinggang Mei,
• Chun Wang,
• Zhigang Zhao,
• Weicheng Yuan and
• Guolin Zhang

Beilstein J. Org. Chem. 2015, 11, 1220–1225, doi:10.3762/bjoc.11.135

• , Southwest University for Nationalities, Chengdu 610041, China 10.3762/bjoc.11.135 Abstract The hemisynthesis of the naturally occurring bioactive flavonoid glycoside icariin (1) has been accomplished in eleven steps with 7% overall yield from kaempferol. The 4′-OH methylation of kaempferol, the 8

• -prenylation of 3-O-methoxymethyl-4′-O-methyl-5-O-prenyl-7-O-benzylkaempferol (8) via para-Claisen–Cope rearrangement catalyzed by Eu(fod)3 in the presence of NaHCO3, and the glycosylation of icaritin (3) are the key steps. Keywords: Claisen–Cope rearrangement; flavonol; icariin; prenylation; regioselectivity

• , amnesia, arthritis, asthenia, impotence, infertility, lumbago and other chronic illnesses [1][2]. Icariin (1), a 3,7-diglycosylflavone (Figure 1), is recognized as the major pharmacologically active ingredient of these plants [3][4], and has been used as the index for quality control of the herbs and