Biomedical Engineering Reference
In-Depth Information
SCHEME 7.1
Two different approaches to generate skeletal diversity.
7.2 SKELETAL DIVERSITY
Skeletal diversity has generally been achieved by two different strategies: (1) a
common intermediate was converted into diverse skeletons under different reaction
conditions (referred to as a reagent-based approach or a differentiating or branch-
ing process), and (2) substrates bearing different appendages were prepared that
preencoded skeletal information (called
-elements), referred to as a substrate-based
approach or folding process (Scheme 7.1) [1]. However, in numerous instances the
approaches are combined, resulting in increased diversity of compounds. One older
example of skeletal diversity is the synthesis of an
,
,
-peptide library [3] that
included
-peptides. Side-chain
amino groups of diaminopropionic and diaminobutyric acids formed the
- and
-peptide bonds in addition to traditional
- and
-peptide bonds of the backbone.
7.2.1 Reagent-Based Strategy: Branching Process
As mentioned above, reagent-based strategy utilizes a common precursor that is
transformed into diverse skeletons as a result of treatment with various reagents. Due
to the diversity of structures and applied chemistries that fall into this category, we
divided individual diversity routes according to the number of core structures and the
type of heterocycle. Most, if not all, chemical routes reported describe the syntheses
of heterocyclic compounds.
7.2.1.1 One Core Structure
In this section we describe the DOS of heterocyclic
compounds that share a core structure. This core molecule is converted into several
different derivatives; however, all of them contain the same central core structure [4].
In medicinal chemistry, core molecules possessing a range of biological activities
are termed
privileged structures
. The term was introduced by Evans et al. in 1988
[5]. Privileged structures are capable of binding to multiple unrelated classes of
