Effect of tertiary amine on the carbodiimide-mediated peptide synthesis.
The effect of tertiary amine (DIEA) on reaction rate and product purity of a carbodiimide/HOBt-mediated peptide synthesis was studied. It was found that very rapid activation can be achieved using carbodiimide/HOBt in non-polar solvents, such as DCM. Although the HOBt is poorly soluble in DCM, the activation proceeds within 2 min, probably forming the HOBt-ester. By such a preactivation followed by a coupling in the presence of DIEA the rate of coupling is comparable with other rapid methods using BOP or TBTU, and no racemization was found in a model coupling (less than 0.1%). For comparison, syntheses of neurotensin by means of different coupling reagents (BOP, TBTU, OPfp-esters) and the DIEA-catalyzed coupling after carbodiimide/HOBt-activation under comparable conditions have shown that these procedures are of the same value in view of coupling efficiency and product purity.
Beyermann
M
M
Institute of Drug Research, Academy of Sciences of the G.D.R.
Henklein
P
P
Klose
A
A
Sohr
R
R
Bienert
M
M
D000588:Amines / Q000737:chemistry*; D000595:Amino Acid Sequence; D002234:Carbodiimides; D055598:Chemical Phenomena; D002621:Chemistry; D005021:Ethylamines; D008752:Methylene Chloride; D008969:Molecular Sequence Data; D009496:Neurotensin / Q000138:chemical synthesis; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D012995:Solubility; D012997:Solvents; D014230:Triazoles
D000588:Amines; D002234:Carbodiimides; D005021:Ethylamines; D010455:Peptides; D012997:Solvents; D014230:Triazoles; D009496:Neurotensin; D008752:Methylene Chloride; C027070:N,N-diisopropylethylamine; C011852:1-hydroxybenzotriazole