Racemization in Peptide Coupling
Activated Nalpha-acylamino acids cyclize to a 5(4H)-oxazolone whose ring proton is acidic enough to be removed by base, scrambling the alpha-stereocenter; Cys and His are the worst offenders, and fragment couplings are far more at risk than stepwise ones. Suppression means minimising base, lowering temperature, using HOAt/Oxyma additives, and avoiding preactivation time.
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Activated Nalpha-acylamino acids cyclize to a 5(4H)-oxazolone whose ring proton is acidic enough to be removed by base, scrambling the alpha-stereocenter; Cys and His are the worst offenders, and fragment couplings are far more at risk than stepwise ones. Suppression means minimising base, lowering temperature, using HOAt/Oxyma additives, and avoiding preactivation time.
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