Organic Chemistry

978 CHAPTER 23 Amino Acids, Peptides, and Proteins

carboxyl group of glycine in preference to reacting with a nonactivated carboxyl group

of another alanine molecule.

The reagent that is most often used to protect the amino group of an amino acid is

di-tert-butyl dicarbonate. Its popularity is due to the ease with which the protecting

group can be removed when the need for protection is over. The protecting group is

known by the acronym t-BOC (pronounced tee-boc).

Carboxylic acids are generally activated by being converted into acyl chlorides

(Section 17.20). Acyl chlorides, however, are so reactive that they can readily react

with the substituents of some of the amino acids during peptide synthesis, creating un-

wanted products. The preferred method for activating the carboxyl group of an N-pro-

tected amino acid is to convert it into an imidate using dicyclohexylcarbodiimide

(DCC). (By now, you have probably noticed that biochemists are even more fond of

acronyms than organic chemists are.) DCC activates a carboxyl group by putting a

good leaving group on the carbonyl carbon.

After the amino acid has its N-terminal group protected and its C-terminal group acti-

vated, the second amino acid is added to form the new peptide bond. The bond

of the tetrahedral intermediate is easily broken (the activated group is a good leaving

C¬O

CH 3

OO

H 2 NCH 2 CO− H 2 NCHCO−

glycine

protect

activate

peptide bond is formed

between these groups

alanine

O

CH 3 C CCH 3 H 2 NCH 2 CO−

CH 3

CH 3

+

O

O C O

CH 3

CH 3

OO

CH 3 C O C NHCH 2 CO− + CO 2 + HO CCH 3

CH 3

CH 3

CH 3

CH 3

O

C O

di-tert-butyl dicarbonate glycine N-protected glycine

proton

transfer

an imidate

CH 3

CH 3

CH 3 C

ONO

OC C

N

NHCH 2 COH

CH 3

CH 3

CH 3 C

N

C

+NH

+

O O

O C NHCH 2 CO− +

CH 3

CH 3

CH 3 C

N

C

NH

O O

O C NHCH 2 CO

N-protected amino acid

dicyclohexylcarbodiimide

DCC

protected

activated

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