Microwave-assisted solid-phase synthesis of 2,5-diketopiperazines: solvent and resin dependence.
Solid-phase synthesis of diketopiperazines (DKPs) was preformed using various combinations of resins (polystyrene, TentaGel, ArgoGel, and PEGA) and solvents (toluene, tert-butyl alcohol, water, and toluene/2-butanol (1:4, v/v). The DKPs were synthesized from solid-phase bound dipeptides via intramolecular aminolysis. Both thermal and microwave-assisted solid-phase synthesis of DKPs gave high yields of products independently of resin and organic solvent used; however, only the PEGA resin resulted in high yields of DKPs in water independent of heating method. The short reaction times, high yields, and the possibility to run reactions in water when an appropriate resin is used makes the microwave-assisted solid-phase synthesis the method of choice. The method should be suitable for solid-phase synthesis of diketopiperazine-based libraries.
Tullberg
Marcus
M
Department of Chemistry, Medicinal Chemistry, Göteborg University, SE-412 96 Göteborg, Sweden.
Luthman
Kristina
K
Grøtli
Morten
M
D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D003500:Cyclization; D008872:Microwaves; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000528:radiation effects*; D012117:Resins, Synthetic / Q000737:chemistry* / Q000528:radiation effects*; D012997:Solvents / Q000737:chemistry / Q000528:radiation effects
D010879:Piperazines; D012117:Resins, Synthetic; D012997:Solvents