and the products isolated. The structures of these products are usually deter-
mined by following the history of the synthesis using the grid references of the
wells and confirmed by instrumental methods (mainly NMR, GC, HPLC
and MS).
The pin array is used in a similar manner to the well array except the array of
crowns is inverted so that the crowns are suspended in the reagents placed in a
corresponding array of wells (Figure 6.6(b) ). Reaction is brought about
by placing the combined pin and well unit in a suitable reaction environment.
The loading of the wells follows the pattern described in Figure 6.8. The parallel
and pin methods are not the only solid support methods of obtaining combina-
torial libraries. A number of other techniques using solid supports have also
been developed.
6.2.2 Furka’s mix and split technique
The Furka method produces the library of compounds on resin beads. It may be
used to make both large (thousands) and small (hundreds) combinatorial lib-
raries. Large libraries are possible because the technique produces one type of
compound on each bead, that is, all the molecules formed on one bead are the
same but different from those formed on all the other beads. Each bead will
yield up to 6 1013 product molecules, which is sufficient to carry out high
throughput screening procedures. The technique has the advantage that it
reduces the number of reactions required to produce a large library.
The beads are divided into a number of equally sized portions corresponding
to the number of initial building blocks. Each starting compound is attached to
its own group of beads using the appropriate chemical reaction (Figure 6.9). All
the portions of beads are now mixed and separated into the number of equal
portions corresponding to the number of different starting compounds being
used for the first stage of the synthesis. One reactant building block is added to
each portion and the reaction carried out by putting the mixtures of resin beads
and reactants in a suitable reaction vessel. After reaction all the beads are mixed
before separating them into the number of equal portions corresponding to
the number of reactants being used in the second stage of the synthesis. One
of the second stage building blocks is added to each of these new portions and the
mixture allowed to react to produce the products for this stage in the synthesis.
This process of mix and split is continued until the required library is synthe-
sized. In peptide and similar polymer library formation where the same building
blocks are used at each step, the maximum possible number of compounds
THE SOLID SUPPORT METHOD 121