Stereoselective synthesis of J-104,118 and J-104,123, novel, potent inhibitors of squalene synthase

Article abstract of DOI:10.1016/0040-4020(96)00850-2

A novel class of squalene synthase inhibitors (J-104,118 and J-104,123) were synthesized efficiently. An amine intermediate 1 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. 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.