Search Results (2)

In the total stereo-controlled synthesis of natural prostaglandins (PGs) and their structural analogs, a vast class of compounds and drugs, known as the lactones, are encountered in a few key steps to build the final molecule, as: δ-lactones, γ-lactones, and 1,9-, 1,11-, and 1,15-macrolactones. After the synthesis of 1,9-PGF_2α and 1,15-PGF_2α lactones, many 1,15-lactones of E₂, E₃, F₂, F₃, A₂, and A₃ were found in the marine mollusc Tethys fimbria and the quest for understanding their biological role stimulated the research on their synthesis. Then 1,9-, 1,11-, and 1,15-PG lactones of the drugs were synthesized as an alternative to the corresponding esters, and the first part of the paper describes the methods used for their synthesis. The efficient Corey procedure for the synthesis of prostaglandins uses the key δ-lactone and γ-lactone intermediates with three or four stereocenters on the cyclopentane fragment to link the PG side chains. The paper describes the most used procedures for the synthesis of the milestone δ-Corey-lactones and γ-Corey-lactones, their improvements, and some new promising methods, such as interesting, new stereo-controlled and catalyzed enantioselective reactions, and methods based on the chemical/enzymatic resolution of the compounds in different steps of the sequences. The many uses of δ-lactones not only for the synthesis of γ-lactones, but also for obtaining 9β-halogen-PGs and halogen-substituted cyclopentane intermediates, as synthons for new 9β-PG analogs and future applications, are also discussed. Full article

Prostaglandins (PGs) with cytoprotective activity were studied for a long time, and a few PGE₁ and PGE₂ stable analogues were promoted as drugs: arbaprostil, enprostil, misoprostol, and rioptostol. Similarly, nocloprost, a 9β-chlorine prostaglandin analogue, and many 9β- and 11β-substituted prostaglandins were synthesized and studied for their biological activity. We previously synthesized new 9β-halogenated prostaglandins with an ester group at the carbon atom 6 (PGs numbering) by the reaction of a δ-lactone intermediate with diols in acid catalysis. These compounds were used in the current molecular docking study to determine their potential cytoprotective (anti-ulcer) activity. The current study was done with the CLC Drug Discovery Workbench 2.4. software and an oxidoreductase enzyme receptor, chosen from the Protein Data Bank, ID: 4KEW (www.rcsb.org). We used two recognized drugs, omeprazole (co-crystallized with the enzyme) and nocloprost, as the standard. The 9β-halogenated prostaglandin analogs were docked. Nocloprost and all 9β-halogenated compounds had docking scores greater than that of omeprazole. The majority of the 9β-halogenated analogs had docking scores even greater than that of nocloprost, indicating that these compounds could have potential cytoprotective (anti-ulcer) activity. A few correlations between docking score and substituents on the prostaglandin skeleton were found. Full article