Racemization
Racemization is always a consideration
in peptide synthesis. Naturally occurring
biologically active amino acids
are almost exclusively found in the L-conformation
at their α-carbon, however
racemization can convert the L-conformation to
the D-conformation. Glycine with an R group equal
to hydrogen does not have a chiral α-carbon.
 |
 |
| L-conformation |
D-conformation |
Removal and reattachment of
the hydrogen atom attached to the α-carbon
represents a potential mechanism for enantiomerization.
During amino acid activation, the acidity of the
α-carbon proton increases. However, this
does not appear to be significant mechanism of
enantiomerization. Another route to enantiomerization
is deprotonation and oxazolone formation.
In general, enantiomerization
through oxazolone formation is rarely encountered
with stepwise synthesis except for histidine and
cysteine. However, special coupling chemistries
for these amino acids have largely circumvented
the problem. |
