Solid-phase S-3CR generates N-substituted α-aminonitriles for the synthesis of α-phenyl-α-(1-piperazinyl) substituted amino acids

K. C. Probst1, G. Jung2
1Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, U.K.
2Institut für Organische Chemie, University of Tübingen, Tübingen, Germany

Tóm tắt

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 α-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 α-aminonitriles with the free piperazine nitrogen when cleaved with acid and the product purities were 72–93%. The α-aminonitriles were easily converted to novel Nɛ – Fmoc-protected α-amino acids with α-(1-piperazinyl) and α-phenyl substituents.

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Tài liệu tham khảo

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