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

Abstract

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.

Ruthenium-Catalyzed Azide Alkyne Cycloaddition Reaction: Scope, Mechanism, and Applications

“…95 The purpose was to prepare suitable building blocks for incorporating into triazole peptidomimetics, and these applications are covered in more detail in chapter 5. Halogenated internal alkynes have been investigated by Fokin and co-workers, affording 5-halo-1,2,3-triazoles that can be further derivatized using palladium-catalyzed cross-coupling reactions.…”

“…A diverse set of 1,5-triazole products can be found in these reports which cover a wide range of targets and target classes including various enzyme inhibitors, [203][204][205][206][207][208][209][210][211][212][213] kinases, [214][215][216][217] proteases, 110,112 antivirals 218 (see also chapter 5.3) G-protein coupled receptors (GPCRs), 219 ion channels, [220][221][222] heat shock proteins, 95 and tRNA ligands. 223 1,5-Triazole derivatives have shown activity against numerous cancer cell lines, 205,215,[224][225][226][227] and against the parasites Trypanosoma cruzi 70,228 and Plasmodium falciparum.…”

Transition Metal‐Catalyzed Cycloaddition of Azides with Internal Alkynes

“…In 2015, Taddei et al demonstrated that in the presence of [Cp*RuCl] 4 , N-Boc-aminopropiolates could smoothly react with aryl or alkyl azides to afford 5-amino-1,2,3-triazole-4-carboxylates with absolute regiocontrol (38 a-38 c in Scheme 22). [37] While the regioselectivity in the reactions of phenyl-involved ynamides was still exclusive (38 d), mixtures of regioisomers were observed in the treatments of ynamides with an alkyl group (38 e & 38e'). This could be mainly because of the polarity variation of the C � C triple bond.…”

General Method of Synthesis of 5-(Het)arylamino-1,2,3-triazoles via Buchwald–Hartwig Reaction of 5-Amino- or 5-Halo-1,2,3-triazoles

“…Among fully substituted 1,2,3-triazoles special attention is focused on 5-amino-1,2,3-triazoles and their 5-arylamino derivatives, which exhibit very promising biological properties such as antiviral, antifungal, antiproliferative and antimetastatic activities. They also serve as activators of potassium channel andchelating agents and have a potential for treating inflammatory kidney diseases ( Figure 1 ) [ 21 , 22 , 23 , 24 , 25 , 26 ].…”