BOP REAGENT| SYNTHETIC COUPLING REAGENT.pptx

BOP Reagent is a synthetic coupling reagent which is used in the coupling of two amino acid for peptide synthesis

1. BOP REAGENT PREPARED BY : SAURAV KR TALUKDAR M PHARM 1 ST SEMESTER DEPT OF PHARMACEUTICAL CHEMISTRY

2. INTRODUCTION TO BOP REAGENT BOP stands for (Benzotriazol-1-yloxytris( dimethylamino )phosphonium hexafluorophosphate) It is a synthetic coupling reagent used in the process of peptide synthesis. It is widely employed to facilitate the formation of amide bonds, particularly in the coupling of amino acids during peptide chain assembly.

3. CHEMICAL STRUCTURE Chemical Formula: C12H22F6N6OP2 The molecular structure of BOP reagent includes the following key components: Benzotriazol-1-yloxy group Tris( dimethylamino )phosphonium group Hexafluorophosphate anion

4. SYNTHESIS OF BOP REAGENT Step 1 : Phosphorus oxychloride ( POCl ₃) is reacted with an excess of dimethylamine to form a tris( dimethylamino )phosphine intermediate.

5. SYNTHESIS OF BOP REAGENT Step 2 : This intermediate is then reacted with 1-Hydroxybenzotriazole ( HOBt ) to produce Benzotriazol-1-yloxytris( dimethylamino )phosphonium chloride.

6. SYNTHESIS OF BOP REAGENT Step 3 : The final step involves exchanging the chloride ion with hexafluorophosphate (PF₆⁻) by treating the phosphonium chloride with a hexafluorophosphate salt to form the BOP ( Benzotriazol-1-yloxytris( dimethylamino )phosphonium hexafluorophosphate) reagent.

7. MECHANISM OF ACTION In peptide synthesis, BOP reagent functions by activating the carboxyl group of one amino acid, allowing it to react with the amine group of another amino acid to form an amide bond. Amide BOP

8. MECHANISM OF ACTION Step 1: Activation of Carboxyl Group : BOP reagent activates the carboxyl group (-COOH) of the incoming amino acid. This activation is necessary for efficient peptide bond formation.

9. MECHANISM OF ACTION Step 2: Formation of Active Ester : In the presence of a base (such as diisopropylethylamine), the carboxyl group of the amino acid reacts with the BOP reagent, producing an activated benzotriazolyl ester . This ester is highly reactive toward nucleophiles like the amino group of the next amino acid

10. MECHANISM OF ACTION Step 3: Nucleophilic Attack by Amino Group : The free amino group (-NH₂) of another amino acid attacks the activated ester, leading to the formation of a amide bond Amide

11. APPLICATION OF BOP Solid-Phase Peptide Synthesis (SPPS) BOP reagent is a popular choice in SPPS due to its compatibility with protecting groups and its ability to efficiently activate amino acids on solid support matrices like polystyrene or polyethylene glycol (PEG). Natural Product Synthesis Its utility extends beyond peptides, as it can be used to synthesize other amide-containing compounds in the construction of natural products and complex organic molecules. Custom Peptide Design It involves the synthesis of specific peptide sequences with desired properties for research, medical, or industrial applications

12. ADVANTAGES & DISADVANTAGES ADVANTAGES OF BOP REAGENT Low Racemization Versatility Fewer Side Reactions DISADVANTAGES OF BOP REAGENT By-product Formation Toxicity Cost

13. REFERENCE Dormoy JR, Castro B, Rabanal F, Giralt E.(2001) “Benzotriazol‐1‐yloxytris ( dimethylamino ) phosphonium Hexafluorophosphate.” Encyclopedia of Reagents for Organic Synthesis. Carpino, L. A., & El-Faham, A. (1995). "BOP Reagent: A Critical Overview of its Applications in Peptide Synthesis." Journal of Organic Chemistry, 60(24), 7511–7515. Bodanszky , M. (1993). "Principles of Peptide Synthesis." 2nd ed. Springer-Verlag.

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