Section 23.9 Strategy of Peptide Bond Synthesis: N-Protection and C-Activation 979group) because the bonding electrons are delocalized, forming dicyclohexylurea, a
stable diamide. [Recall that the weaker (more stable) the base, the better it is as a leav-
ing group; see Section 17.5.]Amino acids can be added to the growing C-terminal end by repeating these two steps:
activating the carboxyl group of the C-terminal amino acid of the peptide by treating it
with DCC and then adding a new amino acid.When the desired number of amino acids has been added to the chain, the protect-
ing group on the N-terminal amino acid is removed. t-BOC is an ideal protecting
group because it can be removed by washing with trifluoroacetic acid and methylene
chloride, reagents that will not break any other covalent bonds. The protecting group is
removed by an elimination reaction, forming isobutylene and carbon dioxide. Because
these products are gases, they escape, driving the reaction to completion.amino acidCH 3CH 3CH 3 COOONCNHOCNHCH 2 CHB+HB+CH 3OH 2 NCHCO−tetrahedral intermediateCH 3 NHCHCH 3CH 3 COOOHNCH 3CNHOCNHCH 2 C−OCCH 3 CH 3CH 3CH 3 CONHCHCO− +OO O NHCNHOCNHCH 2 COdicyclohexylurea
a diamidenew peptide bond- DCC
- H 2 NCHCO−
N-protected dipeptide N-protected tripeptide
ORCH 3NHCHCO−OONHCH 2 CCH 3CH 3CH 3 COOCCH 3CH 3CH 3 COOCCH 3NHCHCO ORNHCHCO−ONHCH 2 CCF 3 COOH
CH 2 Cl 2OO C NHCH 2 CCH 3NHCHCOHOONHCHCN-protected tripeptidetripeptideCH 2HCH 3CH 3 CCH 2CH 3CH 3 CCF 3 COO OHOO CRRCH 3NHCHCOHOONHCHC−+CO 2 +ONHCH 2 C+OH 3 NCH 2 CCH 3NHCHCOHOONHCHCRHB+HB+BRUI23-959-998r2 29-03-2003 1:36 PM Page 979