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

ABSTRACT: A concise and stereoselective total synthesis of the clinically relevant tricyclic prostaglandin D₂ metabolite (tricyclic-PGDM) methyl ester in racemic form was accomplished in eight steps from a readily available known cyclopentene-diol derivative. The synthesis features a nickel-catalyzed Ueno-Stork-type dicarbofunctionalization to generate two consecutive stereocenters, a palladium-catalyzed carbonylative spirolactonization to build the core oxaspirolactone, and a Z-selective cross-metathesis to introduce the (Z)-3-butenoate side chain, a group challenging to introduce through traditional Wittig protocols and troublesome for the two previous total syntheses. A general Z-selective cross-metathesis protocol to construct (Z)-β,γ-unsaturated esters was also developed that has bro

SUBMITTER: Sims HS 

PROVIDER: S-EPMC8766936 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature