Piperazine amide linker for cyclative cleavage from solid support: traceless synthesis of dihydroquinoxalin-2-ones.
A piperazine amide linker for cyclative cleavage from solid support and its use in the traceless solid-phase synthesis of dihydroquinoxalinones are described. Piperazine was attached to Wang resin via a carbamate linkage and acylated with Fmoc-amino acids. Following Fmoc group removal, resin-bound amines were reacted with 1-fluoro-2-nitrobenzenes. The nitro group of the resulting 2-nitroanilines was reduced, and acyclic precursors, in contrast to traditional ester-type linkage, remained attached to the resin. Target dihydroquinoxalinones were obtained either by acid- or microwave-mediated cyclative cleavage. The synthesis provided crude compounds of high purity and enabled the preparation of stable immobilized linear intermediates. The linker is suitable for combinatorial synthesis of compound libraries.
Department of Organic Chemistry, Faculty of Science, Palacký University , 17. Listopadu 12, 771 46 Olomouc, Czech Republic.
Cleopatra
C
Neagoie
Viktor
V
Krchňák
D000215:Acylation; D000577:Amides / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D005449:Fluorenes / Q000737:chemistry; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry*; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000737:chemistry; D012117:Resins, Synthetic / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques / Q000379:methods
D000577:Amides; D000596:Amino Acids; D005449:Fluorenes; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D010879:Piperazines; D011810:Quinoxalines; D012117:Resins, Synthetic; D000077489:Piperazine