Ruthenium-Catalyzed Synthesis of 5‑Amino-1,2,3-triazole-4-carboxylates for Triazole-Based Scaffolds: Beyond the Dimroth Rearrangement

The 5-amino-1,2,3-triazole-4-carboxylic
acid is a suitable molecule
for the preparation of collections of peptidomimetics or biologically
active compounds based on the triazole scaffold. However, its chemistry
may be influenced by the possibility of undergoing the Dimroth rearrangement.
To overcome this problem, a protocol based on the ruthenium-catalyzed
cycloaddition of N-Boc ynamides with azides has been
developed to give a protected version of this triazole amino acid.
When aryl or alkyl azides are reacted with N-Boc-aminopropiolates
or arylynamides, the cycloaddition occurs with complete regiocontrol,
while N-Boc-alkyl ynamides yield a mixture of regioisomers.
The prepared amino acids were employed for the preparation of triazole-containing
dipeptides having the structural motives typical of turn inducers.
In addition, triazoles active as HSP90 inhibitors (as compound 41, IC50 = 29 nM) were synthesized.