Total synthesis of an isoflavone <i>C</i>-glycoside: 6-tert-butylpuerarin

<p>The first total synthesis of an isoflavone <i>C</i>-glycoside (6-<i>tert</i>-butylpuerarin) using commercially available 4,6-di-<i>tert</i>-butylbenzene-1,3-diol as starting material was achieved in five steps with an overall yield of 2.8%. The key intermediate <b>4</b> was obtained by de-<i>tert</i>-butylation of <b>2</b> with trifluoroacetic acid and Friedel-Crafts acetylation of 2-<i>C</i>-β-D-glucopyranoside <b>3</b>. Condensation of <b>4</b> with 4-(benzyloxy)benzaldehyde resulted in the formation of <i>C</i>-glucosylchalcone <b>5</b>, which was cyclized by oxidative rearrangement using (diacetoxyiodo)benzene (DIB) and p-toluenesulfonic acid to obtain the target molecule <b>6</b>. This environmentally friendly and concise synthetic pathway should be applicable to the large-scale synthesis of various isoflavone <i>C</i>-glycosides.