This document discusses an end-on template method for meta C-H activation in pharmaceutical chemistry. The method uses a temporary helper molecule or template to mediate the addition of functional groups to carbon atoms. A metal catalyst like palladium helps facilitate the process. The template approach allows for easier modification of drug molecules by attaching biologically active functional groups at meta positions. Several drug targets that could benefit from this meta C-H activation are discussed, including antihyperlipidemic, GABA agonist, anti-cancer and antihypertensive drugs.

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
 β-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-C–H 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….