Thalidomide metabolites and analogs. Part 2: Cyclic derivatives of 2-N-phthalimido-2S,3S (3-hydroxy) ornithine

E-(5-N-phthaloyl)-2-pentenoic acid benzyl ester was dihydroxylated by a Sha rpless AD-mix protocol followed by mononosylation of the resultant 2R,3S di ol. Azide displacement of the mononosylate followed by protection with the TBDMS group gave the epsilon-N-phthaloyl-substituted-beta-tert-butyldimethy lsilyloxy-alpha-azidocarboxylic acid benzylester. Hydrazinolysis resulted i n removal of the phthalimide group with concomitant lactamization to the 4- silyloxy-3-azidopiperidinones. Staudinger reduction of the azidopiperidinon es followed by N-phthaloylation and hydrolysis of the silyl group afforded the 4'-hydroxylated-6'-deoxythalidomide derivatives. (C) 2000 Elsevier Scie nce Ltd. All rights reserved.