Protection for the AMINE.pptx

Protection & deprotection for the AMINE

1. Protection for the amine group PRESENTED BY- INDRAJIT SAMANTA M.PHARM ( PHARMACEUTICAL CHEMISTRY), 1ST SEM, 1ST YEAR DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, SPER, JAMIA HAMDARD, NEW DELHI ​

2. contents

3. INTRODUCTION CHEMO SELECTIVITY Which functional groups will react REGIO SELECTIVITY Where it will react

4. INTRODUCTION Which functional group reacts first Reaction Condition reagents

5. INTRODUCTION WHAT IS A PROTECTING GROUP? A protecting group (PG) is a molecular framework that is introduced onto a specific functional group (FG) in a poly-functional molecule to block its reactivity under reaction conditions needed to make modifications elsewhere in the molecule . R-FG PG R-FG-PG Free functional group (reactive) MUSK FUNCTIONAL GROUP( Unreactive)

6. Qualities of a Good Protecting Group in Organic Synthesis (a) It should be readily, but selectively introduced to the desired functional group in a poly-functional molecule. (b) It should be stable / resistant to the reagents employed in subsequent reaction steps in which the group being masked (protected) is desired to remain deactivated (protected). (c) It should be capable of being selectively removed under mild conditions when its protection is no longer required TACTICAL CONSIDERATIONS Easy & efficient introduction stable throughout reaction, work up & purification efficient and selective removal under mild conditions should not create any stereo-genic centre

7. Protecting Groups for Amino Groups The basic problem of peptide synthesis is one of protecting the amino group. In bringing about interaction between the carboxyl group of one amino acid and the amino group of a different amino acid, one must prevent interaction between the carboxyl group and the amino group of the same amino acid. In preparing glycyl alanine, for example, one must prevent the simultaneous formation of glycylglycine. Reaction can be forced to take place in the desired way by attaching to one amino acid a group that renders the NH, unreactive

8. Protecting Groups for Amino Groups

9. Protecting Groups for Amino Groups Carbamates as Protecting Groups for Amines : Formation:- CLEAVAGE:

10. Carbamates as Protecting Groups for Amines: t-Butyl carbamate (Boc group):- FORMATION: RR’NH + Me 3 COCOCl Base RR’NCOOCMe 3 CLEAVAGE: RR’NCOOCMe 3 3M HCl RR’NH

11. Carbamates as Protecting Groups for Amines: 9-Fluorenylmethyl carbamate (Fmoc or 9-fluorenylmethyloxycarbonyl ): 9-Fluorenylmethyloxycarbonyl protection is used for an alcohol or amine and it is carried out with an Fmoc-X reagent (X-CI or Nj) in the presence of pyridine or NaHCO3 FORMATION: CLEAVAGE:

12. Benzyl carbamate [benzyloxy-carbonyl or CBZ group (RRNCOOCH2Ph)]:- FORMATION: CLEAVAGES:

13. Amides as Protecting groups for Amines:- Amides are readily prepared from an amine and an acid chloride or anhydride. These are relatively more stable compounds that, classically, are cleaved by heating in strongly acidic or basic solutions. FORMAMIDE: FORMATION: RR’NH + HCOOH DCC, Pyridine RR’NCHO CLEAVAGE:

14. AMIDES AMIDES Amide condensation of phenylacetic acid and benzylamine with various catalysts under sealed conditions FORMATION Direct amide condensation of various carboxylic acids and amines by 8a ( SiO 2

15. Cyclic Imides As Protecting Group For Primary Amines:- Phthalimide:- FORMATION:

16. Cyclic Imides As Protecting Group For Primary Amines:- CLEAVAGE:

17. Other protection for amine

18. Synthetic applications 1) synthesis of dipeptide (glycine alanyl )

19. Application: YU’s synthesis of Paroxetine:

20. Synthetic applications Romero synthesis of HIV-I protease inhibitor:

21. Synthetic applications Synthesis of beta- lactam in preparation of carpetimycin A:

22. Synthetic applications SYNTHESIS OF BETA LACTUM ANTIBIOTIC:

23. Synthetic applications SYNTHESIS OF 4- HYDROXYPHOSPHONINE :

24. Synthetic applications SYNTHESIS OF AZASUGAR:

25. Synthetic applications SYNTHESIS OF OTHER DURGS:

26. REFERENCES: Hanson, J.R.; Protecting Groups in Organic Synthesis; Sheffield Academic Press; pp 8-80. Morrison, R.T.; Boyd R.N.; Organic Chemistry; Prentice-Hall of India Private Limited; Sixth Edition- 2002; pp. 1147. 2,2,6,6-Tetramethylpiperidin-1-yloxycarbonyl: A Protecting Group for Primary, Secondary, and Heterocyclic Amines , Joseph R. Lizza , Maximilian Bremerich , Stephanie R. McCabe, Peter Wipf, Org. Lett.   2018 . https://doi.org/10.1021/acs.orglett.8b02874