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, 123) were synthesized efficiently. An amine intermediate I was synthesized using two distinct methods. First, the racemic amine 1 was synthesized diastereoselectively using a key reaction consisting of the stereo-controlled reduction of the ketone 7 by L-Selectride(R). Second, the optically active amine 1 was synthesized efficiently and enantioselectively using Sharpless dihydroxylation as a key reaction. A stereo-controlled method for synthesizing J-104,123 was developed starting from a commercially available methyl (R)-3-hydroxybutyrate. Copyright (C) 1996 Elsevier Science Ltd.