Prostacyclins biological activity

W. Skuballa, H. Vorbruggen, A new route to 6a-carbacyclin. Synthesis of a stable, biologically active prostacyclin analogue, Angew. Chem. Int. Ed. Engl. 20 (1981) 1046. 

Biomaterial with immobilized prostaglandins show excellent antithrombotic effects by inhibition platelet aggregation [77-81]. However, some of the prostaglandins are too unstable to use. In our study, a stable and biologically active prostacyclin derivative TRK-100 (shown in Scheme 10) was used. 

The eicosanoids are a group of biologically active compounds containing 20 carbon atoms derived from arachidonic acid. The prostaglandins (Section 19.6) and the leukotrienes (Section 9.16) are two types of eicosanoids. Two others are the thromboxanes and prostacyclins. 

Each eicosanoid is associated with specific types of biological activity (Table 29.4). In some cases, the effects oppose one another. For example, thromboxanes are vasoconstrictors that trigger blood platelet aggregation, whereas prostacyclins are vasodilators that inhibit platelet aggregation. The levels of these two eicosanoids must be in the right balance for cells to function properly. 

Dietary fat serves several important nutritional functions. It is the source of essential fatty acids. Members of the n-6 and n-3 (also known as the co-6 and co-3) families of fatty acids are important constituents of cell membranes and serve as precursors of eicosanoids (biologically active compounds such as prostaglandins, thromboxanes, prostacyclins, and leukotrienes). Fat also serves as a carrier for the fat-soluble vitamins, and it is important source of energy. In addition, it has important culinary properties and contributes to the palatability of food. 

The occurrence of highly functionalized furanoid systems either as a key entity or key substructure of more complex molecules in various biologically active natural products, such as the entire class of polyether antibiotics, prostaglandins, prostacyclins, and marine Laurencia metabolites, initiated new developments in their syntheses. 

The two former routes give biologically active compounds of great biological importance, viz. the prostaglandins, thromboxanes, prostacyclin and leukotrienes. 

Carboprostacyclin, 43, a stable and biologically active analogue of prostacyclin (PGI2) provides an additional example of the utility of the Weiss-Cook reaction. The Weiss-Cook reaction product 41 was transformed into the advanced intermediate 42. A Wadsworth-Homer-Emmons reaction provided a method to append the alcohol sidechain to the aldehyde moiety and a Wittig reaction, on the deprotected ketone, introduced the carboxy sidechain for the desired target 43. 

Eicosanoids are a very broad class of natural lipids that contain 20 carbons, are derived from fatty acids, and include the prostaglandins as well as leukotrienes, thromboxanes, and prostacyclins, all common and important biologically active molecules. 

Prostaglandins belong to a larger class of compounds called eicosanoids, which include leukotrienes, prostaglandins, thromboxanes, and prostacyclins, all of which exhibit a wide array of biological activity. 

The nitrogen analogue of prostacyclin (PGH2 Scheme 21) has been synthesized as outlined in Scheme 48. The compound has similar biological activity to the natural product. 

---