@article{7221978,
  abstract     = {{Despite extensive research into peptide synthesis, coupling of amino acids with weakly nucleophilic heterocyclic amines remains a challenge. The need for microwave technology to promote this coupling interferes with the scalability of the process. By applying the microwave-to-flow paradigm, a library of (alpha-aminoacyl)amino-substituted heterocycles was continuously produced at near quantitative conversions and the reaction was scaled up successfully. Various N-Cbz-protected amino acids were activated using BtH/SOCl2 under continuous-flow conditions with excellent yields. Their coupling with heterocyclic amines was accomplished in MeCN-NMP on a preparative scale. However, performing both steps in-line resulted in an inconvenient work-up. Therefore, a two-step approach was taken, isolating the intermediate Bt-activated amino acid via simple filtration. This allows for a solvent switch to DMSO for the coupling reaction which led to excellent conversions for a broad range of substrates.}},
  author       = {{Seghers, Sofie and Van Waes, Frederik and Cukalovic, Ana and Monbaliu, Jean-Christophe and De Visscher, Jeroen and Thybaut, Joris and Heugebaert, Thomas and Stevens, Christian}},
  issn         = {{2062-249X}},
  journal      = {{JOURNAL OF FLOW CHEMISTRY}},
  keywords     = {{microreactor,continuous flow,amino acids,benzotriazole,amide bond formation,N-ACYLBENZOTRIAZOLES,MICRO REACTORS,BETA-PEPTIDES,REAGENTS,ALPHA,HETEROCYCLES,DERIVATIVES,INHIBITORS,DESIGN,FMOC-ALPHA-AMINOACYL)BENZOTRIAZOLES}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{220--227}},
  title        = {{Efficient continuous-flow benzotriazole activation and coupling of amino acids}},
  url          = {{http://dx.doi.org/10.1556/1846.2015.00029}},
  volume       = {{5}},
  year         = {{2015}},
}

Altmetric

View in Altmetric

Web of Science

Times cited: