PyOxP and PyOxB: the Oxyma-based novel family of phosphonium salts.
Recent studies described the great impact of a non-benzotriazolic family of coupling reagents based on ethyl 2-cyano-2-(hydroxyimino)acetate, Oxyma, as a powerful coupling methodology for peptide synthesis. Here we present the synthesis and evaluation of the derived phosphonium salts O-[(1-cyano-2-ethoxy-2-oxoethylidene)amino]-oxytri(pyrrolidin-1-yl) phosphonium hexafluorophosphate (PyOxP) and tetrafluoroborate (PyOxB). Both coupling reagents exhibited higher capacity to suppress racemization in various peptide models and enhanced solubility in DMF and DCM than benzotriazole-based reagents. In addition, the hexafluorophosphate analog PyOxP, combined excellent stability with outstanding efficiency in the assembly of demanding penta and decapeptides that include consecutive Aib residues. Cyclization models revealed the advantages of PyOxP, which rendered a higher percentage of cyclic material than other known potent phosphonium salts.
Subirós-Funosas
Ramon
R
Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10, 08028, Barcelona, Spain.
El-Faham
Ayman
A
Albericio
Fernando
F
D003500:Cyclization; D006868:Hydrolysis; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000737:chemistry*; D011245:Pregnadienes / Q000737:chemistry*; D012995:Solubility; D013237:Stereoisomerism
D009943:Organophosphorus Compounds; D011245:Pregnadienes; C045419:oxyma