Fundamentals of Medicinal Chemistry

synthesis and biological testing but using groups of nine reactants for the first

step will give the amino acid that occupies the second place in the peptide chain.

Further repetition but using groups of nine amino acid reactants in the second

step will identify the third amino acid in the chain.

In order to be effective, deconvolution procedures require that both the

synthesis and assay of the library be rapid. The procedure is complicated

when there is more than one active component in the library. In this case it is

necessary to prepare and test all the possible compounds indicated by deconvo-

lution in order to identify the most active compound in the library.

6.6 Questions

(1) Outline the basic principle underlying combinatorial chemistry. What criteria

should be satisfied by the building blocks used in a combinatorial synthesis?

(2) List the general considerations that should be taken into account when

designing a combinatorial synthesis.

(3) Outline the parallel synthesis technique for carrying out a combinatorial

synthesis. How does this method differ from Furka’s mix and split method?

(4)

(B)

H 2 NCHCONHCHCOOH

R^1 R^2

Outline a design for a combinatorial synthesis for the formation of a com-

binatorial library of nine compounds with the general formula B using the

Furka mix and split method. Outline any essential practical details. Details of

the chemistry of peptide link formation are not required; it is sufficient to say

that it is formed.

(5) Outline the range of encoding methods used to deduce the structures of

compounds produced in a Furka mix and split combinatorial synthesis.

(6) Describe, in general terms, how the technique of deconvolution can be used to

identify the most active component in a combinatorial library consisting of

groups of mixtures of compounds.

130 COMBINATORIAL CHEMISTRY