No abstract

No abstract

No abstract

The total synthesis of the carbocyclic analogue(2) of prostacyclin (1) from cis-bicyclo [3.3.0]octane-3,7dione (3) is described. stance owing to its potent antithrombotic and vasodilatory properties. Since then an increasing number of analogues have been reported in search of potentially therapeutic agent^.^ We now report the total synthesis of the carbocyclic analogue (2) of this important biomolecule. cis-Bicyclo [3.3.0]octane-3,7-dione (3) was converted into the mono-acetal (4)t (95% yield based on 70% conversion)IN 1976 Vane and his associates announced the discovery of prostacyclin ( l ) , l t 2 a rather unstable but exciting sub-

The X-ray structures of pancreatic bovine and porcine phospholipases A2 have been used along with interactive computer graphics to design conformationally rigid, novel compounds (1-meta-hydroxybenzyl-2-substituted acenaphthenes) directed at the active sites of these enzymes. In vitro testing confirmed that the designed compounds are potent inhibitors of the porcine pancreatic phospholipase A2 and exhibit both stereoselectivity and structure-activity relationships that are consistent with the proposed mode of binding. These compounds take advantage of a hydrophobic "slot" positioned between residues Leu-2 and Tyr-69 while positioning hydrogen-bonding functionality directed at the nd1-N of His-48. Experimental evidence shows a regioselective preference for this H-bond acceptor. A second part of the strategy used a tethered amine to displace the essential calcium providing a bisubstrate analog.