Fundamentals of Medicinal Chemistry

NO 2

C

OO−C

O

O−(CH 2 )n−O−Ar RESIN−O

Aryl halide tag

Photolabile carbonate linker

T1 T2 T3 T4 T5 T6

0

Cl Cl Cl

Cl Cl Cl Cl

H

F

H

Tag retention time

T1 T3 T5 T6

0

(c)

(b)

(a)

Figure 6.13 (a) Molecular tags used by Still. Indicates the point at which the tag is

attached to the linker. (b) A hypothetical representation of the GC plots obtained for some aryl

halide tags T 1 to T 6. (c) The tag chromatogram for a hypothetical tagging scheme.

Table 6.3 A hypothetical tagging scheme for the preparation of tripeptides using binary combinations of six tags

Stage

Tag

Glycine (Gly) Alanine (Ala) Serine (Ser)

1T1 T2 T1þT2 2T3 T4 T3þT4 3T5 T6 T5þT6

halide tags allocated as shown in the tagging scheme outlined in Table 6.3 gave the

tag chromatogram shown in Figure 6.13(b). The presence of T1 shows that in the

first stage of the synthesis the first amino acid residue is glycine. This residue will

be attached via its the C-terminus of the peptide if a linker with an amino group

was used and its N-terminus if a linker with an acid group was used. The presence

of T3 shows that the second residue is also glycine, whilst the presence of T5 and

T6 indicates that the third amino acid in the peptide is serine.

6.3.3 Computerized tagging

Nicolaou has devised a method of using silicon chips to record the history of a

synthesis. Silicon chips can be coded to receive and store radio signals in the

form of a binary code. This code can be used as a code for the building blocks of

126 COMBINATORIAL CHEMISTRY