Coupling reagents HBTU

Key words Solid-phase peptide synthesis, SPPS, Fmoc, Boc, Linkers, Coupling reagents, HBTU, HATU, COMU, HOBt, HOAt, Oxyma, BAL... 

Coupling reagents HBTU (2 [(lH-benzotriazol-l-yl)-(dimethylamino)-methylene]-N-methylmethanaminium hexa-fluorophosphate 2sT-oxide), DIG (diisopropylcarbodiimide), HOBt (1-hydroxybenzotriazole), and DIEA N,N-diisopropylethylamine) were from Iris Biotech GmbH or Novabiochem. All other chemicals were obtained from Sigma-Aldrich. 

Coupling reagent HBTU (ISI-[(lif-benzotriazol-l-yl) (dimethylamino)methylene]-AT-methylmethanaminium hexa-fluorophosphate AT-oxide). 

Other coupling reagents, such as HBTU or HATU, are also effective in place of BOP/HOBt as described. 

Method B Alternatively, the branched peptide-resin was synthesized using HBTU/HOBt as coupling reagents. The above mentioned Fmoc amino acids (1.95 mmol) were coupled to Fmoc-Gly-SASRIN-resin (lg, sub. level =0.65 mmol-g1) with HOBt (0.26g, 1.95mmol), HBTU (0.67g, 1.76mmol), and DIPEA (0.63 mL, 3.71 mmol) in DMF without preactivation. The coupling was complete within 1 to 2 h. 

PAL-PEG resin, Fmoc amino acids and coupling reagent N,N -diisopropylethylamine (DIPEA) and fhbcnzotriazolc-/V,/V,Ar,Ar-tetramct.hyl-uronium-hexafluoro-phosphate (HBTU) (Advanced ChemTech, Louisville, KY). 

The first amino acid is coupled onto the resin in the presence of DIPEA, using HBTU as a coupling reagent. 

In the most obvious way, a metal complex can be added to the N terminus of the final peptide on the resin (bottom path in Fig. 3). This requires very similar chemistry as discussed above for solution metallation. The metal complex is treated more or less as another amino acid. HBTU and TBTU are the preferred coupling reagents in this case, also HATU might have advantages in difficult cases. We find that for less reactive metal complexes, e.g., cobaltocenium carboxylic acid, longer activation and coupling times of up to 24 h may be needed. 

Coupling reagents A,A -dicyclohexylcarbodiimide (DCC), A,A -diisopropyl-carbodiimide (DIC), 1-hydroxybenzotriazol (HOBt), and (9-benzotriazolyl-A,A, A, A -tetramethyluronium hexafluorophosphate (HBTU)" (Fluka, or Applied Biosystems, SARF Paris, France). 

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