Catalysis‐Enabled Concise and Stereoselective Total Synthesis of the Tricyclic Prostaglandin D2 Metabolite Methyl Ester

A concise and stereoselective total synthesis of the clinically relevant tricyclic prostaglandin D2 metabolite (tricyclic-PGDM) methyl ester in racemic form was accomplished eight steps from a readily available known cyclopentene-diol derivative. The features nickel-catalyzed Ueno–Stork-type dicarbofunctionalization to generate two consecutive stereocenters, palladium-catalyzed carbonylative spirolactonization build core oxaspirolactone, Z-selective cross-metathesis introduce (Z)-3-butenoate side chain, group challenging through traditional Wittig protocols troublesome for previous syntheses. general protocol construct (Z)-β,γ-unsaturated esters also developed that has broad functional tolerance high stereoselectivity. Additionally, our already accumulated 75 mg valuable material an 18O-tricyclic-PGDM-based assay used clinical settings inflammation.