Page 1278 - Advanced Organic Chemistry Part B - Reactions & Synthesis

1254 the starting point is a collection of beads, each with one initial starting material. After
each reaction step the beads are recombined and divided again. As the collection of
CHAPTER 13
beads is split and recombined during the combinatorial synthesis, each bead acquires
Multistep Syntheses a particular compound, depending on its history of exposure to the reagents, but every
bead in a particular split has the same compound, since their reaction histories are
identical. Figure 13.1 illustrates this approach for three steps, each using three different
reactants. However, in the end all of the beads are together and there must be some
means of establishing the identity of the compound attached to any particular bead.
In some cases it is possible to detect compounds with the desired property while they
are still attached to the bead. This is true for some assays of biological or catalytic
activity that can be performed under heterogeneous conditions.
Another approach is to tag the beads with identifying markers that encode the
sequence of reactants and thus the structure of the product attached to a particular
bead. 61 One method of coding involves attachment of a chemically identifiable tag,

Fig. 13.1. Splitting method for combinatorial synthesis on solid support. Reproduced from
F. Balkenhohl, C. von dem Bussche-Huennefeld, A. Lansky, and C. Zechel, Angew. Chem. Int. Ed.
Engl., 35, 2288 (1996), by permission of Wiley-VCH.

61
S. Brenner and R. A. Lerner, Proc. Natl. Acad. Sci. USA, 89, 5381 (1993).