readily available. Thedisconnectionapproach (see section 10.3.1) may be used
both to identify these starting materials and to define the steps in the pathway.
Alternatively, suitable starting compounds and a route may be determined by
modification of the known synthetic route for a compound with a similar
structure to the target.
The chemical reactions selected for the proposed synthetic pathway will
obviously depend on the structure of the target compound. However, a number
of general considerations need to be borne in mind when selecting these
reactions.
1. The yields of reactions should be high. This is particularly important when
the synthetic pathway involves a large number of steps.
2. The products should be relatively easy to isolate purify and identify.
3. Reactions should be stereospecific, as it is often difficult and expensive to
separate enantiomers. This is a condition that is often difficult to satisfy.
4. The reactions used in the research stage of the synthesis should be adaptable
to large scale production methods (see section 11.2).
An important aspect of all medicinal chemistry synthetic pathway design is
divergency. Ideally, the chosen route should be such that it is relatively easy to
modify the structure of the lead compound either directly or during the course
of its synthesis. This is an economic way of producing a greater range of
analogues for testing and hence increasing the chance of discovering anactive
compound. Initially these modifications would normally take the form of
changing the nature of side chains or introducing new substituents in previously
unsubstituted positions. The synthetic pathway for the preparation of the lead
compound should include stages where it is possible to introduce these new side
chains and substituents. For example, the presence of an amino group in a
structure opens out the possibility of introducing different side chains by
N-acylation (Figure 10.3).
10.2 Asymmetry in syntheses
The presence of a asymmetric centre or centres in a target structure means that
its synthesis requires either the use ofnon-stereoselective reactions and the
ASYMMETRY IN SYNTHESES 205