1. WELCOME

2. PRESENTED BY ANU.S PHARMACEUTICAL CHEMISTRY END-ON TEMPLATE METHOD FOR META C-H ACTIVATION 3. CONTENTS INTRODUCTION CATALYTIC CYCLE FOR META C-H ACTIVATION OLEFINATION APPLICATIONS OF END-ON TEMPLATE METHOD IN CHEMISTRY DRUG TARGETS THAT BENEFIT FROM META C-H ACTIVATION CONCLUSION REFERENCES 4. INTRODUCTION C-H activation Involves replacement of strong terminal C-H bonds with a functional group. 5. Electrophilic aromatic substitution reaction is the basis for many of modification reactions in pharmaceutical compounds. Due to the presence of an electron donating group in the aromatic system, the substitution at the meta position is difficult. End-on template method is a novel approach of substitution of functional groups at meta C-H position. 6. It is a novel meta C-H activation approach in modification of drug molecule. Modifying organic molecule that significantly helps in developing new pharmaceuticals and improving old ones. 7. Method involves Temporary attachment of a helper molecule to one carbon atom, that extends the nearest carbon atom and mediates the addition of a functional group. Metal catalyst like palladium helps in the process. 8. Template H metal catalyst Template H M Cyclophene like pretransition state Functionalization Template Functional group 9. CATALYTIC CYCLE FOR META C-H ACTIVATION OLEFINATION 10. Example for end-on template reaction 11. Meta selective C-H methylation 2,2'-iminobis(4-methoxybenzonitrile) 12. Advantages of end-on template method Easily removable template 13. APPLICATIONS OF END-ON TEMPLATE METHOD IN CHEMISTRY Used to modify compounds like Tetrahydro quinolines Benzoxazines Aniline Benzylamines 2-phenyl pyrazolidines 2-phenylpiperidines etc. 14. Overrides intrinsic electronic and steric bias of molecules -hydride elimination for 1o and 2o alkyls Activates distal C-H bonds 15. DRUG TARGETS THAT BENEFIT FROM META C-H ACTIVATION ANTI HYPERLIPIDEMIC DRUGS 16. GABA AGONIST 17. ANTI CANCER DRUG 18. ANTI HYPERTENSIVE DRUG 19. CONCLUSION End-on template method is applied directly to many medicinally relevant compounds Helps easier modification of existing organic compounds by attaching biologically active functional groups to a drug molecule. 20. REFERENCES Wan, L.; Dastbaravardeh, N.; Li, G.; Yu, J. -Q. J. Cross- coupling of remote meta-C-H bonds directed by a U-shaped template, Journal of the American Chemical Society, 2013 Dec 4;135(48):18056-9 Ri-Yuan Tang,Gang Li & Jin-Quan Yu, Conformation-induced remote meta-CH activation of amines, Nature 507, 215 220 (13 March 2014) Daugulis O, Do HQ, Shabashov D, Palladium- and copper- catalyzed arylation of carbon-hydrogen bonds, Accounds of Chemical Research, 2009 Aug 18;42(8):1074-86 21. Chen X, Engle KM, Wang DH, Yu JQ , Palladium(II)-catalyzed C-H activation/C-C cross-coupling reactions: versatility and practicality, Angewandte Chemie International Edition, 2009;48(28):5094-115 Ackermann L, Vicente R, Kapdi AR, Transition-metal-catalyzed direct arylation of (hetero)arenes by C-H bond cleavage, Angewandte Chemie International Edition, 2009;48(52):9792-826 All information were collected from various sources, only for educational purpose. 22. THANK YOU.