Biomedical Engineering Reference
In-Depth Information
SCHEME 6.18
Couple/pair approach to macrocyclic peptidomimetics using azido-amines
and alkyne-acids for the CuAAC process.
The major contribution to stereochemical and scaffold diversity was recognized
to be from the build phase, taking advantage of the wide variety of natural and
unnatural
-amino acids amenable for the build step of the synthesis.
Using principal components analysis (PCA), the authors demonstrated that the library
of the 12 synthesized analogs covered a distinct and broad chemical space compared
to a set of 657 approved drugs.
-,
-, and
6.6 CONCLUSIONS
The combinatorial concept is evolving to diversity-oriented synthesis (DOS) with
the aim of expanding the chemical diversity around the molecular scaffolds and
addressing structural complexity, in addition to the appendage diversity on a fixed
cyclic scaffold traditionally taken into account in classic combinatorial chemistry.
Peptidomimetics may represent a privileged set of compounds, due to the importance
of peptide-protein and protein-protein in biological processes, and the diversity-
oriented synthesis of small-molecule peptidomimetics may give access to collections
of new chemotypes bearing a high level of structural diversity. Accordingly, recent
papers on DOS approaches in the field of peptidomimetics have appeared in the
