Purine-substituted imidazolium mesomeric betaines and their tautomeric N-heterocyclic carbenes. Formation of a cyclic borane adduct

Abstract

6-Chloropurine and 2,6-dichloropurine were reacted with N1-substituted imidazoles to give purin-6-yl substituted imidazolium salts, respectively. Deprotonation of the 1-methylimidazolium derivative resulted in the formation of the corresponding stable conjugated mesomeric betaine, whereas the 1-phenyl,- 1-vinyl- and 1-(2-hydroxyethyl) derivatives proved to be unstable. In situ generation of the mesomeric betaines by caesium carbonate in the presence of sulfur and selenium, however, gave the thiones and the selenones of the tautomeric purine-substituted imidazol-2-ylidene, respectively. Its anionic N-heterocyclic carbene was formally trapped by reaction with triethylborane at high temperatures as a cyclic boron adduct which is the first representative of a new heterocyclic ring system. DFT calculations gained insight into the electronic properties of the N-heterocyclic carbenes substituted by π-electron donators. Results of a single crystal X-ray analysis of the boron adduct are presented.

Computational and Experimental Druggability Assessment of Human DNA Glycosylases

“…The remaining 21 compounds were subjected to dose–response assays, where the chemotypes of TH8187 and TH6319, as well as adenine analogues of CGP-74514A were confirmed to be low μM inhibitors of NEIL1 (Figure 6C). 50,91…”

“…The remaining 21 compounds were subjected to dose−response assays, where the chemotypes of TH8187 and TH6319, as well as adenine analogues of CGP-74514A were confirmed to be low μM inhibitors of NEIL1 (Figure 6C). 48,89 DSF Fails to Validate Target Engagement of Biochemical Activity Screen Hits. Differential scanning fluorimetry 90,91 is a fast and readily available method to experimentally assess protein druggability and target engagement in vitro.…”

3‐Aryl Substituted 1‐Methylquinolinium Salts as Carbene Precursors

“…To prepare the starting compounds, 3‐bromoquinoline 6 was subjected to a Suzuki–Miyaura reaction with aryl boronic acids in the presence of 10 % Pd(CH 3 COO) 2 as a catalyst and K 3 PO 4 as a base in toluene/water solution to give 3‐aryl quinolines 8a – c (Scheme ). Related to previous works,[22c], dimethyl sulfate was used as a convenient reagent for the quaternization of 8a – c to give the salts 9a – c in high yields. 50 µL of nitrobenzene were used as a catalyst in these reactions.…”

“…In continuation of our interest in the different types of conjugation and their consequences for N‐heterocyclic carbene formation, we examined the influence of substituents at C3 of quinolinium on trapping reactions of quinolin‐2‐ylidenes generated from them. We chose different aryl and ethynyl substituents which are in conjugation to the quinolinium ring.…”

Zn2+ detection of a benzimidazole 8-aminoquinoline fluorescent sensor by inhibited tautomerization

“…In continuation of our interest in metal adducts and metal complexes of heterocycles such as mesomeric betaines and N -heterocyclic carbenes 23 in catalysis, 24 metal recovery and recycling, 25 we report here on a new 8-aminoquinoline based chemosensor L1 for the Zn 2+ detection. L1, bearing a benzimidazole moiety, was acquired through a simple two-step synthesis and exhibits a prototropic tautomerization, which was spectroscopically proven to be inhibited by Zn 2+ ions.…”