Peptide Synthesis Flashcards
What does the dipeptide, Leu-Phe look like?
Why can’t we just couple Leu and Phe together?
- It would result in a mixture of all 4 possible products (Phe-Phe, Phe-Leu, Leu-Phe, Leu-Leu), we need to use protecting groups
We cannot use acyl chlorides for amino acid amide bond formation, as we getting scrambling of sterochemistry
Why?
The proton next to the R group is very acid (deprotonate) - due to how electron withdrawing the chlorine group is
hence a racemixture can be formed
We can form amide bonds from carboxylic acids and amines using an activated ester approach
How?
- TCP is okay leaving group but not as electron-withdrawing
- Add TCP to compound will activate it
How do we remove the protecting groups when we have done an activated ester approach to amide bond formation from carboxylic acids and amines
- Hydrogenate then treat with acid
- (TFA - Trifluoroacetic acid)
- Results in Leu-Phe
We can form amide bonds from carboxylic acids and amines using an mixed anhydride approach
How?
- Carbonate is a good leaving group
How do we remove the protecting groups when we have done a mixed anhydride approach to aminde bond formation from carbonxylic acids and amines
- Hydrogenate and treat with acid
- (is now better way to do this using DCC)
We can also use DCC and HOBt to couple peptide bonds
What are the structures for DCC and HOBt
- Dicyclohexylcarbodiimide: dehydrating agent
- Hydroxybenzotriazole: Nucleophilic catalystic, acid OH - stopping racemization, good LG
The first part of the DCC coupling for peptide bond formation, is the production of this activated ester What is the mechanism?
Once the activated ester is formed during DCC coupling for peptide bond formation, the final dipeptide can be formed
What is the mechanism
(the BtOH is regenerated - hence used as catalyst)
