1. Introduction of Combinatorial Chemistry
5th Year Pharmacy

2. Definition
A branch of applied chemistry concerned with the rapid synthesis and screening of large numbers of different but related chemical compounds generated from a mixture of known building blocks in order to recover new substances optimally suited for a specific function

3. Other definition
that make it possible to prepare a large number (tens to thousands or even millions) of compounds in a single process. These compound libraries (products ) can be made as mixtures, sets of individual compounds or chemical structures generated in silico

10. Disadvantages High affected molecular size, solubility,
Achiral products

15. 1- Solid Phase Synthesis
A common combinatorial technique uses organic synthesis on solid support.  Linker groups are attached to resin beads in the solid phase and the reactants are passed over in solution to make the intermediates and a final detachment-from-resin reaction is run to get the desired product out of the column.   

16. SUPPORTS AND LINKERS
Most solid-state combinatorial chemistry is conducted by using polymer beads 10 to 750 µm in diameter.
The polymers are inert, except for the functional groups to which the molecules are attached. In general, the compounds 10 be synthesized are not attached directly to the polymer molecules.

18. They are usually attached using a "linker""
moiety that :
a) enables attachment in a way that can be easily reversed without destroying the molecule that is being synthesized and
b ) allows some room for rotational freedom of the molecules attached to the polymer

19. The types of solid supports that are used include
Poly styrene resins,
TentaGel resins
Polyacyamide resins
Glass & Ceramic resins

28. Mixed Combinatorial Synthesis
There 20 amino acids
AA1 + AA AA1-AA2 ( 20 )n
n=2
20 X 20 = 400 DIPEPTIDES
AA1 + AA2 + AA AA1-AA2-AA3 ( 20 )3
20 X 20 X20 = 8000 TRIPEPTIDES
Home work calculate mixed combinatorial synthesis of Tetrapeptides ?

37. DETECTION, PURIFICATION, AND ANALYSIS
Detection, analysis, and purification of combinatorial libraries
places high demands on exiciting analytical techniques
because {a) the quantities to be analyzed are very small,
sometimes pico-moles of materials (b) the analysis should
be non destructive, to allow recovery of the compound if
possible, and c) the methods must be suitable for rapid
parallel analysis
Chromatographic methods used ( HPLC – MS).
FT-IR ( Fourier transmission Infra-red )spectroscopy
NMR ( Nuclear Magnetic Resonance ) Spectroscopy