Enantioselective Solid-Phase Peptide Synthesis Using Traceless Chiral Coupling Reagents and Racemic Amino Acids

Authors

  • Beata Kolesinska,

    Corresponding author
    1. Institute of Organic Chemistry, Technical University of Łodz, Zeromskiego 116, PL-90-924 Łodz, (phone: +48-42-6313151; fax: +48-42-6365530; , )
    • Institute of Organic Chemistry, Technical University of Łodz, Zeromskiego 116, PL-90-924 Łodz, (phone: +48-42-6313151; fax: +48-42-6365530; , )

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  • Katarzyna Kasperowicz-Frankowska,

    1. Institute of Organic Chemistry, Technical University of Łodz, Zeromskiego 116, PL-90-924 Łodz, (phone: +48-42-6313151; fax: +48-42-6365530; , )
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  • Justyna Fraczyk,

    1. Institute of Organic Chemistry, Technical University of Łodz, Zeromskiego 116, PL-90-924 Łodz, (phone: +48-42-6313151; fax: +48-42-6365530; , )
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  • Zbigniew J. Kaminski

    Corresponding author
    1. Institute of Organic Chemistry, Technical University of Łodz, Zeromskiego 116, PL-90-924 Łodz, (phone: +48-42-6313151; fax: +48-42-6365530; , )
    • Institute of Organic Chemistry, Technical University of Łodz, Zeromskiego 116, PL-90-924 Łodz, (phone: +48-42-6313151; fax: +48-42-6365530; , )

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Abstract

The enantioselective condensing reagent 4,6-dimethoxy-1,3,5-triazine (DMT)/strychnine/BFequation image was obtained by treatment of 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) with strychnine tetrafluoroborate. The reagent was useful under typical conditions of solid-phase peptide synthesis (SPPS) with enantiomerically homogeneous substrates. By SPPS, desired dipeptides were obtained in 84–94% yield using 4 equiv. of racemic Fmoc-Ala, Fmoc-Phe, and/or Fmoc-Tyr for 1 equiv. of Wang resin loaded with Gly, Ala, Leu, Phe, Glu(tBu), and/or Pro, respectively. For all three Fmoc-protected amino acids, the configuration of the enantiomer preferred under SPPS conditions was independent of the structure of the acylated component and identical to that established in condensations proceeding in solution. In all cases, the enantiomer ratios L/D (er) were in a similar range, and varied from 9 : 92 to 2 : 98 for alanine, and from 90 : 10 to 100 : 0 for aromatic amino acids. The synthesis of Ac-L-Lys(Ac)-D-Ala-D-Ala-OH from racemic Fmoc-Ala gave an L/D ratio of 10 : 90 for the esterification of Wang resin, and 0 : 100 for the formation of peptide bonds.

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