9-o-methanoprostaglandin-i and Stroke

Isocarbacyclin is a valuable synthetic analogue of prostacyclin with potential neuroprotective effects for the treatment of ischemic stroke. Herein, we describe the synthesis of isocarbacyclin and bicyclic analogues in only 7-10 steps, with the ω-side chain diversified at a late stage. A combination of new reaction design, function-oriented synthesis, and late-stage diversification led to a series of compounds that were tested for their neuroprotective activities. Efforts toward the synthesis of tricyclic analogues of isocarbacyclin, using the same combination of metal-catalyzed reactions, is also described.

Topics: Animals; Brain Ischemia; Bridged Bicyclo Compounds; Epoprostenol; Mice; Neurons; Neuroprotective Agents; Stereoisomerism; Stroke