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Enantioselective Solid‐Phase Peptide Synthesis Using Traceless Chiral Coupling Reagents and Racemic Amino Acids
Author(s) -
Kolesinska Beata,
KasperowiczFrankowska Katarzyna,
Fraczyk Justyna,
Kaminski Zbigniew J.
Publication year - 2012
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.201200426
Subject(s) - chemistry , reagent , enantiomer , enantioselective synthesis , peptide synthesis , amino acid , tetrafluoroborate , peptide , chiral derivatizing agent , racemization , yield (engineering) , alanine , stereochemistry , combinatorial chemistry , organic chemistry , chiral column chromatography , catalysis , ionic liquid , materials science , biochemistry , metallurgy
The enantioselective condensing reagent 4,6‐dimethoxy‐1,3,5‐triazine (DMT)/strychnine/BF $\rm{{_{4}^{-}}}$ 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( t Bu), 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.