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Introduction of Combinatorial
5th Year Pharmacy
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
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
High affected molecular size, solubility, •
Achiral products •
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.
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.
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
The types of solid supports that
are used include
Poly styrene resins, •
TentaGel resins •
Polyacyamide resins •
Glass & Ceramic resins •
Mixed Combinatorial Synthesis
There 20 amino acids •
AA1 + AA2
AA1-AA2 ( 20 )n
20 X 20 = 400 DIPEPTIDES
AA1 + AA2 + AA3
AA1-AA2-AA3 ( 20 )3
20 X 20 X20 = 8000 TRIPEPTIDES
Home work calculate mixed
combinatorial synthesis of
Tetrapeptides ?
Detection, analysis, and purification of combinatorial •
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 •