Solid-phase synthesis of 1,2,5-trisubstituted 4-imidazolidinones.
An efficient method for the preparation of 1,2,5-trisubstituted 4-imidazolidinones is presented. The synthetic approach is based on the formation of an N-[1-(benzotriazol-1-yl)alkyl] moiety on the amino group of a MBHA resin-bound amino acid. The nucleophilic substitution of the benzotriazole group with an amidic nitrogen results in the formation of a five-membered imidazolidinone ring. The reaction is nonstereospecific and produces diastereomers in ratios that vary depending on the substituents on the ring. A variety of N-alpha-alkylated amino acids were cyclized with aromatic, aliphatic, and heterocyclic aldehydes to determine optimal reaction conditions and to select building blocks for the future preparation of a large, diverse range of individual trisubstituted imidazolidinones as well as a mixture-based combinatorial library.
Rinnová
Markéta
M
Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, California 92121, USA.
Vidal
Agnès
A
Nefzi
Adel
A
Houghten
Richard A
RA
D000596:Amino Acids / Q000138:chemical synthesis; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D003500:Cyclization; D007093:Imidazoles / Q000138:chemical synthesis*; D012117:Resins, Synthetic
D000596:Amino Acids; D007093:Imidazoles; D012117:Resins, Synthetic