Short Total Synthesis of Δ-Prostaglandin J and Related Prostaglandins. Design, Synthesis, and Biological Evaluation of Macrocyclic Δ-Prostaglandin J Analogues.

Comprised of a large collection of structurally diverse molecules, the prostaglandins exhibit a wide range of biological properties. Among them are Δ-prostaglandin J (Δ-PGJ) and Δ-prostaglandin J (Δ-PGJ), whose unusual structural motifs and potent cytotoxicities present unique opportunities for chemical and biological investigations. Herein, we report a short olefin-metathesis-based total synthesis of Δ-PGJ and its application to the construction of a series of designed analogues possessing monomeric, dimeric, trimeric, and tetrameric macrocyclic lactones consisting of units of this prostaglandin. Biological evaluation of these analogues led to interesting structure-activity relationships and trends and the discovery of a number of more potent antitumor agents than their parent naturally occurring molecules.