SYNTHESIS OF BICYCLIC KETONES IN PROSTAGLANDINS AND THEIR ANTIMITOTICACTIVITY

The synthesis of a second ring in the prostaglandin structure, located at positions C-11 and C-13, has been accomplished starting from prost aglandin A(2). Also an efficient enantioselectivity was obtained throu gh the conjugate addition of carbanions at position C-11, together wit h the stereospecificity of a Claisen rearrangement at position C-13. E valuation of the inhibitory effects on the proliferation of the K-562 cell line, in vitro, is presented. A structure-activity relationship i ndicated that alterations of the functional groups incorporated in the second ring of the prostaglandin structure affected their hydrophobic ity. The antimitotic activity for prostanoids 7b, 7c and 7e have shown substantial improvements in their activities according to their ID50 values (12.5, 9.0 and 1.12 mu g/ml), respectively). Attention is calle d to the importance of derivative 7a in terms of its high potency, det ermined by its ID50 values (0.35 mu g/ml).