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The Effect of Counterion and Tertiary Amine on the Efficiency of N ‐Triazinylammonium Sulfonates in Solution and Solid‐Phase Peptide Synthesis
Author(s) -
Kolesinska Beata,
Rozniakowski Kamil K.,
Fraczyk Justyna,
Relich Inga,
Papini Anna Maria,
Kaminski Zbigniew J.
Publication year - 2015
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201402862
Subject(s) - chemistry , reagent , amine gas treating , peptide synthesis , steric effects , counterion , sulfonate , yield (engineering) , solid phase synthesis , combinatorial chemistry , tertiary amine , organic chemistry , peptide , dimethylformamide , protecting group , aminolysis , ion , biochemistry , materials science , alkyl , solvent , metallurgy , catalysis , sodium
A collection of N ‐triazinylammonium sulfonates, designed according to the concept of “superactive esters”, was obtained by treatment of ammonium sulfonates with 2‐chloro‐4,6‐dimethoxy‐1,3,5‐triazine. The structure of the tertiary amine as well as sulfonate anion influenced their reactivity and stability in N , N ‐dimethylformamide (DMF) solution. The reagents were successfully used in solution‐ and solid‐phase synthesis of Z‐, Boc‐, and Fmoc‐protected peptides containing natural and unnatural sterically hindered amino acids as well as in [2+1] fragment condensation approaches, yielding the final products in 80–100 % yield and high optical purity. In manual SPPS of the [Aib] 2 [Aib] 4 ‐enkephalin analogue and the ACP(65–74) peptide fragment VQAAIDYINEG, several sulfonates yielded peptides significantly faster than TBTU or HATU. Comparative analyses demonstrated that 4‐(4,6‐dimethoxy‐1,3,5‐triazin‐2‐yl)‐4‐methylmorpholinium 4‐toluenesulfonate was the most versatile reagent in a wide range of coupling procedures.