STEREOSELECTIVE SYNTHESIS OF J-104,118 AND J-104,123, NOVEL POTENT INHIBITORS OF SQUALENE SYNTHASE

A novel class of squalene synthase inhibitors (J-104, 118 and J-104, 1 23) were synthesized efficiently. An amine intermediate I was synthesi zed using two distinct methods. First, the racemic amine 1 was synthes ized diastereoselectively using a key reaction consisting of the stere o-controlled reduction of the ketone 7 by L-Selectride(R). Second, the optically active amine 1 was synthesized efficiently and enantioselec tively using Sharpless dihydroxylation as a key reaction. A stereo-con trolled method for synthesizing J-104,123 was developed starting from a commercially available methyl (R)-3-hydroxybutyrate. Copyright (C) 1 996 Elsevier Science Ltd.