Does this reaction look familiar? It should! 2-amino-3-hydroxypropanoic acid and 2,6-
diaminohexanoic acid are serine and lysine, respectively—in this reaction, we are forming a peptide
bond. If we treat them as generic amino acids, this is the reaction:
Both of these molecules have a carboxylic acid (which has an acidic hydrogen and an
electrophilic carbonyl carbon) and an amino group (which is nucleophilic). The first molecule also
has a hydroxyl group; the second has an additional amino group and a long alkane chain.There are no additional reagents listed. Therefore, it will be the properties of the two reactants
alone that determine how the reaction will proceed.Either of the two molecules could act as the nucleophile in this reaction, and either could be
the electrophile. The most reactive species are likely the nucleophilic amino groups attacking the
electrophilic carbonyl carbon.The first step of this reaction will be nucleophilic attack by the amino group on the
electrophilic carbonyl carbon. Carbon cannot have five bonds, so the carbonyl group will have to
open up. The hydroxyl group on the carboxylic acid is a poor leaving group, but proton
rearrangements in the molecule turn the hydroxyl group into water, improving its leaving group
ability. Then, the carbonyl will reform, kicking off the water molecule as a leaving group.We might ask why the hydroxyl group on 2-amino-3-hydroxypropanoic acid doesn’t react.
Remember that more oxidized groups tend to be more reactive, and the carboxylic acid is
significantly more oxidized than the hydroxyl group. Another question to consider is which of the
amino groups of 2,6-diaminohexanoic acid will react. This is a question that is perhaps best
answered retrospectively; in this case, the amino group closer to the carbonyl will react because
the resulting product will be stabilized by resonance.