Question 60

The dipeptide, Gln-Gly, on treatment with CH$$_3$$COCl followed by aqueous work up gives:

The dipeptide is written as

$$H_2N{-}CH(CO{-}NH_2){-}CH_2{-}CH_2{-}C(O)NH{-}CH_2{-}COOH$$
(N-terminus)                        (peptide bond)        (C-terminus)

The two functional groups that can, in principle, react with $$CH_3COCl$$ are

1. the free α-amino group at the N-terminus, $$H_2N{-}$$
2. the terminal carboxylic acid group, $${-}COOH$$.

Facts to remember

• Acyl chlorides acylate a free amine easily, giving an amide (acetylation).
• Carboxylic acids can form mixed anhydrides with $$CH_3COCl$$, but these anhydrides are hydrolysed back to the parent acid during the aqueous work-up.
• The nitrogens already present in amide linkages (peptide bond and$$-CONH_2$$ side chain of Gln) are far too weakly nucleophilic to be acylated under these mild conditions.

Step-wise reaction

$$H_2N{-}$$ of Gln attacks the carbonyl carbon of $$CH_3COCl \; \rightarrow$$ tetrahedral intermediate $$\rightarrow$$ loss of $$Cl^-$$ gives the N-acetylated amide.

No lasting change occurs at the carboxyl terminus; any transient anhydride is hydrolysed in the work-up to regenerate $$-COOH$$.

Hence the only permanent change is replacement of the N-terminal hydrogen by an acetyl group.

Product (Option A):
$$CH_3CONH{-}CH(CO{-}NH_2){-}CH_2{-}CH_2{-}C(O)NH{-}CH_2{-}COOH$$

Therefore, the dipeptide Gln-Gly gives its N-acetyl derivative on treatment with $$CH_3COCl$$ followed by water.

Option A which is: the N-acetylated dipeptide (Ac-Gln-Gly).

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