Chapter 21, Problem 21.76P

Interpretation Introduction

(a)

Interpretation:

How to synthesize the given peptide sequence is to be determined.

Concept introduction:

Proteins are large molecules that are constructed from the amino acids. The amino acids are joined by group characteristics of amides in a stable protein.  Since amides are least reactive acid derivative, it requires relatively extreme conditions to hydrolyze them. To synthesize protein, various amino acids are coupled by dehydration, which is catalyzed by DCC. (Remember DCC is a good dehydrating agent, so it is used as a coupling agent in many reactions.) In this reaction, the ${\text{NH}}_{\text{2}}$ group of the one amino acid and ${\text{CO}}_{\text{2}}\text{H}$ group of another amino acid is coupled to form a new amide bond (peptide bond). To carry out the reaction selectively, other reactive groups of the respective amino acids must be protected. For the protection of an amino group, Cbz or Z protecting group is used for the protection of a carboxylic acid group of another amino acid; the benzyl (Bn) protecting group is used because both protecting groups are removed in one step, i.e., by the treatment of ${\text{H}}_{\text{2}}\text{/ Pd}$. In the protection step, an amino acid is treated with benzyl chloroformate ($\text{Z-Cl}$) to protect an amino (${\text{NH}}_{\text{2}}$) group of respective amino acids and to protect ${\text{CO}}_{\text{2}}\text{H}$ group; the corresponding amino acid is treated with benzyl alcohol ($\text{Bn-OH}$) in the presence of the strong acid, which is nothing but a Fisher esterification reaction. The protected form of both groups is carbamate and an ester respectively. To get a proper sequence peptide linkage, the amino group of the first amino acid is protected and a carboxylic acid group of second amino acid is protected, which gives the peptide sequence, first amino acid-second amino acid.

Interpretation Introduction

(b)

Interpretation:

How to synthesize the given peptide sequence is to be determined.

Concept introduction:

Proteins are large molecules that are constructed from the amino acids. The amino acids are joined by group characteristics of amides in a stable protein.  Since amides are least reactive acid derivative, it requires relatively extreme conditions to hydrolyze them. To synthesize protein, various amino acids are coupled by dehydration, which is catalyzed by DCC. (Remember DCC is a good dehydrating agent, so it is used as a coupling agent in many reactions.) In this reaction, the ${\text{NH}}_{\text{2}}$ group of the one amino acid and ${\text{CO}}_{\text{2}}\text{H}$ group of another amino acid is coupled to form a new amide bond (peptide bond). To carry out the reaction selectively, other reactive groups of the respective amino acids must be protected. For the protection of an amino group, Cbz or Z protecting group is used for the protection of a carboxylic acid group of another amino acid; the benzyl (Bn) protecting group is used because both protecting groups are removed in one step, i.e., by the treatment of ${\text{H}}_{\text{2}}\text{/ Pd}$. In the protection step, an amino acid is treated with benzyl chloroformate ($\text{Z-Cl}$) to protect an amino (${\text{NH}}_{\text{2}}$) group of respective amino acids and to protect ${\text{CO}}_{\text{2}}\text{H}$ group; the corresponding amino acid is treated with benzyl alcohol ($\text{Bn-OH}$) in the presence of the strong acid, which is nothing but a Fisher esterification reaction. The protected form of both groups is carbamate and an ester respectively. To get a proper sequence peptide linkage, the amino group of the first amino acid is protected and a carboxylic acid group of second amino acid is protected, which gives the peptide sequence, first amino acid-second amino acid.