Synthesis of (−)-agathic acid and (−)-copalic acid from andrographolide via a regioselective Barton-McCombie reaction

The first synthesis of the ent-labdane diterpenoid (−)-agathic acid (1) with antibacterial activity is described. A chiral pool approach was employed with a linear sequence of 14 steps starting from readily available and inexpensive andrographolide. The regioselective deoxygenation in terms of Barton-McCombie free radical reaction completed a key step in the synthesis. (−)-Copalic acid (2), an analogue of (−)-agathic acid, has been conveniently synthesized from the key intermediate 7 in five steps.

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