Enantiospecific synthesis of (1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid by a modified Corey-Link reaction

(1S,2S,5R,6S)-2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY354740) was synthesised enantiospecifically from a sugar derived enantiomerically pure cyclopentenone, The alpha-amino acid stereogenic centre was formed by reacting the ketone with chloroform anion and then the alcohol so formed was reacted with sodium azide/DBU in methanol to give an azido eater. Critically, this modified Corey-Link reaction gives the opposite stereochemical outcome to the traditional Bucherer-Bergs and Strecker reactions. The azide was reduced and acylated, the 1,2 diol deoxygenated and the protecting groups removed to give LY354740 with an e.e.> 98%. (C) 1998 Elsevier Science Ltd. All rights reserved.