Biomedical Engineering Reference
In-Depth Information
SCHEME 6.12
Skeletal diversity using the chemistry of amino aldehydes according to a
couple/cyclization process.
formation led to divergent pathways affording skeletal diversity (Scheme 6.12). The
starting materials for this process were derived from amino acids, boronic acids, and
readily available hydroxyl aldehydes, and the use of supported reagents facilitated
isolation of the products, thus allowing this chemistry to be open to high-throughput
synthesis.
6.4.4 Scaffolds from Amino Carbonyl and Sugar Derivatives
The contribution of Guarna and Trabocchi to the development of methods for the
identification of small-molecule modulators of protein function focused on the gener-
ation of peptidomimetic libraries from amino acid and sugar derivatives in a diversity-
oriented fashion. Accordingly, the chemistry of amino carbonyls was applied in the
generation of heterocycles, taking advantage of amino acid and sugar derivatives as
building blocks. This is a powerful approach to accessing chemical and geometrical
diversity, given the high number of stereocenters and the multifunctionality of such
compounds, as also demonstrated by literature reports on the use of such substrates
to access combinatorial libraries of heterocyclic compounds [27].
We envisaged the application of selected building blocks from the chiral pool to
develop a DOS strategy to access constrained and stereochemically-rich morpholine-
based heterocycles according to the build/couple/pair approach. The morpholine ring
is of special interest, as it represents a common motif among the various structures
employed by medicinal chemists [28]. In fact, the morpholine moiety is embedded in
