A General Catalyst Controlled Route to Prostaglandin F2_α

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Catalysis

Background:

• Prostaglandin F2α (PGF2α) and its analogues are crucial therapeutics.
• Existing synthetic routes often lack efficiency and stereochemical control.

Purpose of the Study:

• To develop a general, catalyst-controlled synthetic route to PGF2α and analogues.
• To achieve high stereoselectivity in key bond-forming reactions.

Main Methods:

• Utilized Rh-catalyzed dynamic kinetic asymmetric Suzuki-Miyaura coupling for stereoselective C-C bond formation.
• Employed Pd-catalyzed Tsuji-Trost alkylation and iodolactonization for installing final stereocenters.

Main Results:

• Synthesized advanced intermediates with 3 contiguous stereocenters in 99% ee and as a single diastereoisomer.
• Demonstrated control over absolute stereochemistry via ligand selection.
• Successfully synthesized intermediates for analogues like bimatoprost, latanoprost, fluprostenol, and cloprostenol.

Conclusions:

• The developed route offers a versatile and highly stereoselective method for prostaglandin synthesis.
• This strategy provides efficient access to PGF2α and valuable analogues for drug development.