Solid-phase S-3CR generates N-substituted alpha-aminonitriles for the synthesis of alpha-phenyl-alpha-(1-piperazinyl) substituted amino acids.
Structurally diverse amino acids were prepared as versatile synthons for combinatorial chemistry. Using an optimized solid-phase synthesis by Strecker-three-component-reaction (S-3CR), two different polymer linker constructs carrying piperazine were investigated. (a) Acrylate derived base-labile linker yielded alpha-aminonitriles with N-alkylated piperazines via Hofmann elimination after quarternisation with an alkyl halide. The crude product purities were in the range of 54-87%. (b) A urethane type linker yielded alpha-aminonitriles with the free piperazine nitrogen when cleaved with acid and the product purities were 72-93%. The alpha-aminonitriles were easily converted to novel Nepsilon) - Fmoc-protected alpha-amino acids with alpha-(1-piperazinyl) and alpha-phenyl substituents.
Probst
K C
KC
Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, UK.
Jung
G
G
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D009570:Nitriles / Q000737:chemistry*
D000596:Amino Acids; D009570:Nitriles