title: Combinatorial solution-phase synthesis of (2S,4S)-4-acylamino-5-oxopyrrolidine-2-carboxamides.
abstract: Solution-phase combinatorial synthesis of (2S,4S)-4-acylamino-5-oxopyrrolidine-2-carboxamides was studied. First, di-tert-butyl (2S,4S)-4-amino-5-oxopyrrolidine-1,2-dicarboxylate hydrochloride was prepared as the key intermediate in five steps from (S)-pyroglutamic acid. Acylation of the amino group followed by acidolytic deprotection gave (2S,4S)-4-acylamino-5-oxopyrrolidine-2-carboxylic acids, which were then coupled with amines to furnish a library of (2S,4S)-4-acylamino-5-oxopyrrolidine-2-carboxamides. Four coupling reagents, BPC, EEDQ, TBTU, and PFTU, were tested for the amidation reactions in the final step. Amidations with EEDQ and TBTU led to the desired carboxamides. On the other hand, BPC and PFTU were not suited, since diketopiperazines were sometimes obtained instead of the desired carboxamides.
authors.affiliation: Faculty of Chemistry and Chemical Technology, University of Ljubljana, Askerceva 5, P.O. Box 537, 1000 Ljubljana, Slovenia.
authors.forename: Crt
authors.initials: C
authors.lastname: Malavasic
authors.forename: Blaz
authors.initials: B
authors.lastname: Brulc
authors.forename: Petra
authors.initials: P
authors.lastname: Cebasek
authors.forename: Georg
authors.initials: G
authors.lastname: Dahmann
authors.forename: Niklas
authors.initials: N
authors.lastname: Heine
authors.forename: David
authors.initials: D
authors.lastname: Bevk
authors.forename: Uros
authors.initials: U
authors.lastname: Groselj
authors.forename: Anton
authors.initials: A
authors.lastname: Meden
authors.forename: Branko
authors.initials: B
authors.lastname: Stanovnik
authors.forename: Jurij
authors.initials: J
authors.lastname: Svete
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D009682:Magnetic Resonance Spectroscopy; D011761:Pyrrolidonecarboxylic Acid / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000577:Amides; D011761:Pyrrolidonecarboxylic Acid