Solid-phase synthesis of substituted imidazoline-tethered 2,3-diketopiperazines, cyclic ureas, and cyclic thioureas.
Efficient methods for the solid-phase synthesis of imidazoline-tethered 2,3-diketopiperazines, cyclic ureas, and cyclic thioureas are described. Following the exhaustive reduction of resin-bound dipeptides derived from orthogonally protected diamino acids, the primary amine of the resulting tetraamines was selectively protected with Dde. The compounds were then selectively cyclized via their secondary amines with three different diimidazole derivatives ((COIm)(2), COIm(2), CSIm(2)). Upon Dde removal, the compounds were selectively N-acylated and dehydratively cyclized with POCl(3) to afford the imidazoline-tethered analogues in moderate yield and high purity. These procedures have been extended to prepare mixture-based combinatorial libraries. Details of the selection of building blocks for preparation of the positional scanning libraries based on the "libraries from libraries" approach are discussed.
Acharya
A N
AN
Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, CA 92121, USA.
Ostresh
J M
JM
Houghten
R A
RA
D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D054659:Diketopiperazines; D004791:Enzyme Inhibitors / Q000138:chemical synthesis; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D007093:Imidazoles / Q000737:chemistry; D010879:Piperazines / Q000138:chemical synthesis; D012117:Resins, Synthetic / Q000737:chemistry; D013890:Thiourea / Q000138:chemical synthesis; D014508:Urea / Q000138:chemical synthesis
D054659:Diketopiperazines; D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D007093:Imidazoles; D010879:Piperazines; D012117:Resins, Synthetic; D014508:Urea; D013890:Thiourea