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Proceedings of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010P-Triazinylphosphonium Sulphonates as Coupling Reagents forPeptide Synthesis in SolutionBeata Kolesinska, Olga Cieslak, Inga Relich, andZbigniew J. KaminskiInstitute of Organic Chemistry, Technical University of Lodz, 90-924, Lodz,Zeromskiego 116, PolandIntroductionN-Triazinylammonium tetrafluoroborates and sulphonates were found highly efficientcoupling reagents useful in the peptide synthesis in solution and solid phase (SPPS) [1].Herein, we attempted to expand the family of triazine based coupling reagents by includinga new generation of coupling reagents based on P-triazinylphosphonium salts 5.Results and DiscussionP-Triazinylphosphonium sulfonates 5 were obtained by treatment of 2-chloro-4,6-dimethoxy-1,3,5-triazine with sulfonates of tertiary phosphine 3 in the presence of sodiumbicarbonate (Figure 1).R 1R 1 + R 4 -SO -3R 2 P + R 4 -SO 3 HR 2 PHR 3 2 R 3 31R 2ClRP + R3 R 14 -SO -3NNNNON4ONaHCO 3Fig. 1. Synthesis of P-triazinylphosphonium sulfonates 5.The modular structure of triazine condensing reagents made possible to create the library ofP-triazinylphosphonium sulfonates 5a-i (Figure 2). The library was prepared from salts ofmethanesulfonic acid, trifluoromethanesulfonic acid, camphorosulfonic acid, p-toluenesulfonicacid with tributylphosphine and thiphenylphosphine.NH 2OH-CH 2 SO 3 n-BuSO- 3n-Bu--CH n-Bun-Bu3 SO 3CF 3 SO 3n-BuO n-Bu P + n-Bun-Bu P + n-Bu n-Bu P + n-Bu n-Bu P + n-Bu SO- 3n-Bu P + n-BuN NN NN NN NN NO N OO N O O N O O N OO N ODMT/Bu 3 P/CsO - (76%) DMT/Bu 3 P/TsO - (81%) DMT/Bu 3 P/MsO - (65%) DMT/Bu 3 P/TfO - (51%) DMT/Bu 3 P/NafO - (69%)5a 5b 5c 5d 5e-SOPh Ph3Ph PhPh PhPh Ph++CHPPhPP2 SOCH 33 SO -+CF 3 SO --+3 3 PPhPhPhON NN NN NN NO N OO N OO N OO N ODMT/PPh 3 /TsO - (67%) DMT/PPh 3 /MsO - (77%) DMT/PPh 3 /TfO - (65%) DMT/PPh 3 /CsO - (60%)5f 5g 5h 5iFig. 2. Library of P-triazinylphosphonium sulfonates 5a-i.Peptide synthesis using 5a-i as coupling reagents proceeded under mild conditionsequivalent to those which were profitable in the case of N-triazinylammoniumtetrafluoroborates and sulphonates [1]. Participation of triazine „superactive ester” 6 asactive species has been documented in condensations mediated by 5a-i. AllP-triazinylphosphonium sulfonates were found useful as coupling reagents. The mostversatile of them were found 5b and 5f, affording dipeptides in 78-89% yield (see Table 1).ON5O124