Prostaglandin Syntheses by Three‐Component Coupling. New Synthetic Methods (49)

Abstract

The role played by prostaglandins (PGs) in the human body is bewitching. Following the elucidation of their structures in the early 1960s, tremendous efforts were made for the realization of an efficient chemical synthesis, since a sufficient supply of such very rare, naturally occurring local hormones relies solely on their total synthesis. Of the many synthetic routes described in the literature, the majority of which are linear or sequential in nature, the Corey synthesis is perhaps the most versatile; so far more than 5000 prostaglandin analogues have been prepared and have been tested biologically. Some natural prostaglandins and their analogues are already in clinical use. In view of the continuing expansion of this field, we have been fascinated with the concept of developing a highly convergent entry to prostaglandins based on a new strategy. The discovery of a highly enantioselective method for the reduction of prochiral ketones and the elaboration of a procedure for double vicinal CC‐coupling with enones have enabled a one‐pot synthesis of the complete prostaglandin skeleton by linking a chiral 4‐oxygenated 2‐cyclopentenone unit and two side‐chain blocks. This approach is efficient and flexible and allows the direct production of all the naturally occuring prostaglandins and a wide spectrum of analogues.