New Reactions of Tropylium Salts with 4-Nitrobenzohydrazide,Semicarbazide, Thiosemicarbazide,and N-Benzylurea

Russian Journal of Organic Chemistry - Reactions of tropylium tetrafluoroborate with 4-nitrobenzohydrazide, semicarbazide hydrochloride, thiosemicarbazide, and N-benzylurea afforded the...     

Synthesis of lupeol derivatives and their antileishmanial and antitrypanosomal activities

The natural product lupeol 1 was isolated from aerial parts of Vernonia scorpioides with satisfactory yield, which made it viable to be used as starting material in semisynthetic approach. Ten lupeol derivatives 2–11 were prepared by classical procedures. Including, five new esters derivatives 7–11, which were obtained by structural modifications in the isopropylidene fragment. All semisynthetic compounds and lupeol 1–11 were confirmed by ¹H NMR, ¹³C NMR and HRMS. Their antiprotozoal activity was evaluated in vitro against L. amazonensis and T. cruzi. Derivative 6 showed the best antitrypanosomal activity (IC₅₀ = 12.48 μg/mL) and the lowest cytotoxic derivative (CC₅₀ = 161.50 μg/mL). The mechanism of action of the most active derivatives (4, 6 and 11) is not dependent from the enzyme trypanothione reductase.     

Dynamics of Bacteriorhodopsin in the Dark-Adapted State from Solution Nuclear Magnetic Resonance Spectroscopy

To achieve efficient proton pumping in the light-driven proton pump bacteriorhodopsin (bR), the protein must be tightly coupled to the retinal to rapidly convert retinal isomerization into protein structural rearrangements. Methyl group dynamics of bR embedded in lipid nanodiscs were determined in the dark-adapted state, and were found to be mostly well ordered at the cytosolic side. Methyl groups in the M145A mutant of bR, which displays only 10 % residual proton pumping activity, are less well ordered, suggesting a link between side-chain dynamics on the cytosolic side of the bR cavity and proton pumping activity. In addition, slow conformational exchange, attributed to low frequency motions of aromatic rings, was indirectly observed for residues on the extracellular side of the bR cavity. This may be related to reorganization of the water network. These observations provide a detailed picture of previously undescribed equilibrium dynamics on different time scales for ground-state bR.     

Reconciling Electrostatic and n→π* Orbital Contributions in Carbonyl Interactions

Interactions between carbonyl groups are prevalent in protein structures. Earlier investigations identified dominant electrostatic dipolar interactions, while others implicated lone pair n→π* orbital delocalisation. Here these observations are reconciled. A combined experimental and computational approach confirmed the dominance of electrostatic interactions in a new series of synthetic molecular balances, while also highlighting the distance-dependent observation of inductive polarisation manifested by n→π* orbital delocalisation. Computational fiSAPT energy decomposition and natural bonding orbital analyses correlated with experimental data to reveal the contexts in which short-range inductive polarisation augment electrostatic dipolar interactions. Thus, we provide a framework for reconciling the context dependency of the dominance of electrostatic interactions and the occurrence of n→π* orbital delocalisation in C=O⋅⋅⋅C=O interactions.     

Transition-Metal Catalysis of Triene 6π Electrocyclization: The π-Complexation Strategy Realized

Triene 6π electrocyclization, wherein a conjugated triene undergoes a concerted stereospecific cycloisomerization to a cyclohexadiene, is a reaction of great historical and practical significance. In order to circumvent limitations imposed by the normally harsh reaction conditions, chemists have long sought to develop catalytic variants based upon the activating power of metal–alkene coordination. Herein, we demonstrate the first successful implementation of such a strategy by utilizing [(C₅H₅)Ru(NCMe)₃]PF₆ as a precatalyst for the disrotatory 6π electrocyclization of highly substituted trienes that are resistant to thermal cyclization. Mechanistic and computational studies implicate hexahapto transition-metal coordination as responsible for lowering the energetic barrier to ring closure. This work establishes a foundation for the development of new catalysts for stereoselective electrocyclizations.     

Phenazine Radical Cations as Efficient Homogeneous and Heterogeneous Catalysts for the Cross-Dehydrogenative Aza-Henry Reaction

The redox activity of molecular phenazine catalysts has been previously exploited for aerobic oxidative amine homo- and cross-coupling reactions. In this contribution, we have extended the reaction scope of this novel type of organocatalyst and used them in the cross-dehydrogenative aza-Henry coupling of isoquinolines with nitromethane under aerobic conditions. Additionally, we have designed and prepared a novel porous organic polymer by cross-linking of tetrakis(4-bromophenyl)silane and dihydrophenazine through Pd-catalyzed Buchwald-Hartwig cross-coupling. This new type of heterogeneous catalyst, apart from being robust and easily reusable, also showed outstanding catalytic activities and improved selectivity compared to its molecular counterpart. A plausible reaction mechanism was proposed based on spectroscopic and kinetic measurements.