Conformational Landscape of α-Halopropiophenones Determined by nJC-H NMR Reveals Unexpected Patterns and Geometric Constraints.

The conformational features of α-halopropiophenones were investigated to understand the influence of α-halogens on conformation through hyperconjugative interactions, electrostatics, and steric factors. Using NMR, C-H scalar coupling constants were measured in different solvents, revealing a pattern in the conformational equilibria, which we validated by computational means. This behavior arises largely from hyperconjugative effects with the exception of the fluoro-derivatives, which are also influenced by steric and electrostatic interactions. In all cases, the contribution to hyperconjugation of the α-halo ketones is driven by the oxygen lone pair (rather than the C-X bond), which donates electron density to the adjacent C-C bonds. Additionally, C-Cα bond rotation generates distortions in the side chain, responsible for destabilization, thus affecting system conjugation. These structural features identified for the α-halo ketones are also reflected in their reactivity, which is distinct from that expected for nucleophilic addition.

Synthesis of 1,3,4-oxadiazoles with 4-methoxynaphthalene ring: discovering new compounds with antimicrobial activity.

Background: Paracoccidioidomycosis (PCM) is a systemic infection caused by Paracoccidioides spp. (Pb). PCM can be associated or clinically confused with tuberculosis (TB), another pulmonary infection, caused by Mycobacterium tuberculosis (Mtb). Futhermore, the long treatment time of TB and PCM and the cases of TB drug resistance impose difficulties for the cure of these diseases. Results: New 1,3,4-oxadiazoles containing the 4-methoxynaphthalene ring were synthesized and their antimicrobial activity was evaluated against Pb and Mtb. The derivative 6n (with 2-hydroxy-5-nitrophenyl subunit) is the most promising of the series. Conclusion: The 1,3,4-oxadiazole 6n can be used as a prototype drug candidate, with anti-Pb and anti-MTb activities, showing a broad-spectrum profile for the treatment of both pulmonary infections.

Controlled Pyrazole-Hydrazone Annulation: Regiodivergent Synthesis of 1H- and 2H-Pyrazolo[3,4-d]pyridazinones.

An efficient and controlled site-selective annulation of 3,5-diethoxycarbonyl 4-hydrazonyl pyrazoles is described. The relative proportion of the products is affected by hydrazone intermediate configuration, reaction temperature, and Lewis acid employed. At a temperature of 110-120 °C, the reaction preferentially afforded 1H-pyrazolo[3,4-d]pyridazin-7(6H)-ones, whereas using Yb(OTf)3 in MeCN reflux, 2H-pyrazolo[3,4-d]pyridazin-7(6H)-ones were favored. Computational investigations were performed to clarify the mechanism and the origin of the regiodivergence.

Conformational Isomerism of 3-Chalcogenomethyl-N-Methyl-2-Pyrrolidinones: Insights from NMR Spectroscopy and Molecular Modeling.

A conformational analysis of N-methyl-2-pyrrolidinone 3-substituted by methoxyl, thiomethoxyl, and selenomethoxyl is reported by means of 1H nuclear magnetic resonance spectroscopy and electronic structure calculations. The five-membered ring has an envelope conformation with the α-carbonyl substituent being able to assume two positions: pseudo-axial and pseudo-equatorial. In vacuum, the calculations pointed to the pseudo-axial conformer as the most stable one, and this preference increases with the size of the substituent and a decrease in its electronegativity. Natural bond orbital analysis evidenced the importance of electron delocalization on the stability, and a principal component of analysis (PCA) plot of the hyperconjugative interactions revealed the main ones. Steric and electrostatic effects were also investigated by energy decomposition analysis.

Molecular docking and panicolytic effect of 8-prenylnaringenin in the elevated T-maze.

The purpose of this study was to investigate the effects of the chronic administration of a racemic mixture of 8-prenylnaringenin (8-PN) on rats submitted to the elevated T-maze (ETM) model of generalized anxiety and panic disorders. The selective serotonin (SERT) reuptake inhibitor fluoxetine was used as a positive control. Rat locomotion was assessed in a circular arena following each drug treatment. The administration of racemic 8-PN for 21 d in rats increased one-way escape latencies from the ETM open arm, indicating a panicolytic effect. To evaluate the interactions of 8-PN with monoamine transporters, a docking study was performed for both the R and S configurations of 8-PN towards SERT, norepinephrine (NET) and dopamine transporters (DAT). The application of the docking protocol showed that (R)-8-PN provides greater affinity to all transporters than does the S enantiomer. This result suggests that enantiomer (R)-8-PN is the active form in the in vivo test of the racemic mixture.

Monoterpene indole alkaloids from Palicourea crocea.

Two new monoterpene indole alkaloids, named croceaines A (1) and B (2), were isolated from the leaves of Palicourea crocea. The structures of 1 and 2 were elucidated by means of spectroscopic methods.