Answer to Question #131638 in Organic Chemistry for Shaakila

Question

What problems might you foresee if you tried to synthesize L-alanyl-L-valine directly from its two component amino acids? How might you solve this?

Answer 1

 

There is nothing to stop alanine coupling with itself, or valine coupling with itself to form L-alanyl-L-alanine and L-valyl-L-valine respectively. 

There is also no reason why any of the above dipetides that are formed could not undergo a further coupling reaction to form tripeptides, tetrapeptides etc. 

The reaction is also likely to need forcing conditions since one is attempting to form an amide between an amine and a carboxylic acid. This is likely to result in racemisation of asymmetric centres.

Due to these problems, it is necessary to protect the amino group of one amino acid and the carboxylic acid of the other before a coupling reaction is attempted. It is also important to have coupling reagents (e.g. dicyclohexylcarbodiimide) in order to achieve milder, non-racemising conditions.