Parallel synthesis,

1. By: Satyendra yadav

2.  Parallel synthesis leads to a discrete library
by simultaneous addition of reactants in
different reaction vessels and parallel
handling of each library sample.
 Parallel synthesis is a method by which
library construction occurs in distinct spaces
on an array, such that each member of a
library is defined by its position on that
array.

3.  An inherent property of this methodology is
that the structure of a library member can
be deduced from its position on the array.
Because of this method's suitability for
automation and ease of deconvolution it is
increasingly becoming the basis of many
research groups' approach to library
construction.
 Deconvolution is the process whereby the complexity
of an active solid phase pool is unraveled through
iterative synthesis of smaller pools while tracking the
new location of the desired activity. The final iteration
is made of individual compounds and the structure of
the active component can be determined.

4.  Conversely, a pool library is a set of
compounds which are obtained as mixtures,
or library pools, at the end of the synthesis.
 Two methods can be used for parallel
synthetic methods they are;
1. The multipin method
2. The teabag method

5.  In parallel procedures an array of different
substances are simultaneously prepared. A series of
peptides epitopes were synthesized in an apparatus
developed for this purpose.
 The multipin apparatus had a block of wells serving
as reaction vessels and cover plate with mounted
polyethylene rods fitting into well. The first amino
acid was attached to the end of polyethylene rods
(pins) grafted with derivatized polyacrylic acid.The
solutions of protected amino acid coupling reagent
were added to the wells. The peptides formed on the
pins immersed into solutions. The sequence of
peptides depended on the order of amino acids of
added to the wells. The peptides were screened after
deprotection without leaving them from the pins.

6.  Different version of parallel synthesis was
developed in 1985 by Houghten for preparing
array of peptides. The beads of the solid support
were enclosed in permeable plastic bags, then
placed for coupling into a reaction vessel
containing the solution of amino acid & the
coupling reagent. All operations, including
removal of protecting groups, couplings,
washings & even the cleavages were performed
on solid supports enclosed in bags. This
procedure has significant advantages.
 All those bags which needed the attachment of
the same amino acid (eg. Alanine) were grouped
together, placed into the same reaction vessel,&
the coupling could be done in a single operation.

7.  Manual or automated approaches can be used for the
parallel preparation of tens to hundreds of analogues of a
biologically active substrate. The products are synthesized
using reliable coupling and functional group
interconversion chemistry and are progressed to screening
after removal of solvent and volatile by-products. Parallel
and orthodox synthesis is compared below.

8.  Orthodox synthesis usually involves a multistep sequence,
e.g. from A through to the final product D, which is
purified and fully characterised before screening. The next
analogue is then designed, guided by the biological activity
of the previous compound, prepared, and then screened.
 This process is repeated to optimize both activity and selectivity.
 In contrast parallel analogue synthesis involves reaction
of a substrate S with multiple reactants, R1, R2, R3 …
Rn, to produce a compound library of n individual
products SR1, SR2, SR3 … SRn. The library is screened,
usually without purification, and with only minimal
characterisation of the individual compounds, using a
rapid throughput screening technique.

9.  Panlabs have recently disclosed an interest in
making large number of compounds as
individual components using parallel, reliable
solution chemistry. Reactions are pushed to
completion by the use of excess quantities of
the reactive reagent, and are isolated by
solvent - solvent extraction. There is no
further purification, and thus they prefer to
describe these samples as "reaction
products".

10.  Each compound is substantially “pure“ in its
location
 Defined location provides the structure of a
certain compound
 Easier biological evaluation
 Applicable only for medium libraries (several
thousand compounds)