Biobased Pyrazine-Containing Polyesters

A set of 12 first-in-class, biobased pyrazine-containing polyesters was synthesized based on dimethylpyrazine dipropionic acid. These new diacid monomers were obtained from underutilized nitrogen-rich biomass. The polyester materials were synthesized via a two-step melt transesterification-polycondensation procedure with molecular weights between 12 300 and 47 500 g/mol and dispersities between 1.9 and 2.3. Six of the obtained polymers were amorphous and six were semi-crystalline. The thermal properties of the materials were studied; thermal degradation was found to take place at the monomer degradation temperature. The effect of methyl groups on the glass transition temperature was investigated, and the materials were found to behave mostly as aliphatic polyesters in this regard. The melting points of the methyl-substituted polyesters were found to be high and within the range of those of current high-performance polyesters. These materials are thus a welcome addition to current biobased polyesters

Syntheses, pharmacological evaluation and molecular modelling of substituted 6-alkoxyimidazo 1,2-b pyridazines as new ligands for the benzodiazepine receptor

A series of 2,3-disubstituted-6-alkoxyimidazo[1,2-b] has been synthesized and evaluated for in vitro affinity for the benzodiazepine receptor (BZR). 3-(Benzamidomethyl or substituted benzamidomethyl)-6-methoxy-2-(3,4-methylenedioxyphenyl)imidazo[1,2-b]pyridazines were found to be the most potent BZR ligands (eg, 4a, IC50 7 nM; 4e, IC50 14 nM; 4v, IC50 8 nM). Imidazo[1,2-b]pyridazines unsubstituted in the 3-position, or containing builder alkoxy groups in the 6-position, were found to bind less strongly to the BZR. Selected compounds from the series were identified from in vitro GABA-shift experiments as BZR agonists. Molecular modelling has been employed to identify the common pharmacophoric points of lipophilic and hydrogen bonding, ligand-receptor interaction and areas of steric hindrance for these substituted imidazo[1,2-b]pyridazines at the BZR

The Forgotten Pyrazines: Exploring the Dakin–West Reaction

Pyrazines are an underreported class of N-heterocycles available from nitrogen-rich biomass presenting an interesting functional alternative for current aromatics. In this work, access to pyrazines obtained from amino acids by using the 90 year old Dakin-West reaction was explored. After a qualitative screening several functional proteinogenic amino acids proved good substrates for this reaction, which were successfully scaled to multigram scale synthesis of the corresponding intermediate alpha-acetamido ketones. Subsequently, the conditions towards pyrazine formation using delta-amino-levulinic acid were optimized, and these were employed to synthesize a relevant set of five functional dimethylpyrazines in high purity. These pyrazines can be considered a versatile toolbox of aromatic building blocks for a wide range of applications, such as in the synthesis of polymers or metal-organic frameworks