Question

Melanocyte-inhibiting factor is a tripeptide derivative, also known as Pro-Leu-Gly-NH2. It has antidepressant and anti-Parkinsonian effects. Design the synthesis of this compound from amino acids Pro, Leu, and Gly. (Hint: protection and deprotection are needed for the precise synthesis).

2. Melanocyte-inhibiting factor is a tripeptide derivative, also known as Pro-Leu-Gly- NH2. It has antidepressant and anti-Parkinsonian effects. Design the synthesis of this compound from amino acids Pro, Leu, and Gly. (Hint: protection and deprotection are needed for the precise synthesis).

Answer 1

Answer with explanation is given below :

COM Answer & for peptide bond synthesis, the major challenge is to connect the amino acids in correct sequence. propre example, two amino acids (l) andll) can combine with four different possibilites and we get four different peptides as shown on HN c OH + hrncro-on IH -OH C-OH 4 Nc COM н IN 4

n The desired peptide bonds can be formed by following steps: Step 1.7 The number of possibilities can be reduced by protecting group, which are molecules which reacts easily and also removed easily after reaction. Both nitrogen of one amino acid and Carbonylic group of other amino acid is protected as: c017 -CH con + Nitrogen-PG s Port 0 au and then con + carboxylic-PG Hihe coor 1 h where PG — Pootecting group Two Step 2=> to protected give a amino acids peptide bond are then coupled (amide boond) as :- pa a ion + H₂ Na I-H2O B=0 PG H Peptide bond

group, Step 3= gives De protection the of final amine required and carbonylic pepticle ast 2 PG-1 an-cho-Po Depoolection ction - R2 Required beebide group is Benzylony carbonyl generally used amine protecting Carbonylic protecting group It is forming protected by esters Deprotection of olysis by Deprotection amine group is done by catalytic hydrogen- reacting with Has Pd/c of carbonylic group is done by hydrolysis in base.

Hens, required amino acids arve → Glycine (Gly), Leucine Here, required amino acids are: Glycine (Gly, Leucine (Leu) and Proline (Poo). Glycine(sy) → Heath the Leucine Clau] > Hoge tum nista N 10 1 2. I Required structure ataucture ? ILI INH HN-

Step Protection of methanol . by carbonyl and group of acidic solution ast Glycine (Gly) by in Hochi H-Q lite ed NHL Ho NH. G OCH Hof H3 H Proton Transfer 0 methanol) 126 Nite 내3

Leucine by Stettin Protecting amine. group of Benzyl ony corrbonyl-ehlourele con Hotel Deprotonation Hillinų Step 3: Coupling of l) &(1) - i Mt + HOT int 1 2.0 HILINH insmok e r

setite :- De protection of amine, group by Har Padle. HINH2 INH of mu amine group proline : tel amine .: - Protection of OH Benzylouy carbonyl Poroline chloride step 6): Coupling of (11) and (U) : me mode Automotive e || NH.

a ): Amine group is deprotected by H2/Pd, c. (catalytic hydrogenation) 2 I JH₂, Pdle Step (8) > Addition 1. Ho condition gives of the ammonia (NH3) in acidic final product as UN JUNK NH3 Acid (HCl) Proton Ten I (hard Bolest