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The application of quantum‐based NMR methods for the structural elucidation of natural and unnatural products has grown significantly. However, accurately calculating the conformational landscape of flexible molecules with intricate intramolecular hydrogen bonding (IHB) networks continues to be a major challenge. In this work, we thoroughly studied the effect of entropic contributions (trough Gibbs free energies calculations) in the DP4+ performance. Our results show that to solve biased systems with strong IHB interactions requires computing the Boltzmann contributions using Gibbs free energies computed with at least triple‐ξ basis set and SMD solvation model. In response to this finding, we have updated our DP4+App, a user‐friendly Python applet that automates the entire process of calculating DP4+ probabilities. In the new version, the program allows for calculating of conformational contributions at any selected theory level, using either SCF or Gibbs free energies. [ABSTRACT FROM AUTHOR]

Diels‐Alder between nitroalkenes derived from a sugar scaffold and cyclopentadiene were examined. Depending on chemical structure of nitroalkene and polarity of solvent used, the reaction proceeded via the formation of a nitronate intermediate. Cyclic nitronates highly functionalized were obtained as chemically stable and stereochemically pure compounds. [3,3] sigmatropic shift of these ones afforded the Diels Alder cycloadducts in quantitative yield. Mechanistic aspects of reaction between nitroalkenes and cyclopentadiene has been studied using DFT computational methods. Nitronate derivatives are attractive intermediates and open the way for the construction of valuable compounds with potential applications. [ABSTRACT FROM AUTHOR]

An experimental and computational study (including DFT calculations and distortion/interaction analysis) was conducted to assess the effect of the nitrone structure in the outcome of dipolar 1,3‐cycloadditions with levoglucosenone, a biomass derived chiral enone. While B3LYP/6‐31G* (the most popular method for modeling these reactions according to our literature search) provides qualitatively good results, large outliers were found for some systems versus experimental data. An exhaustive exploration of other levels allowed us to determine the most appropriate ones to predict simultaneously reactivity and selectivity. The systematically predicted high exo selectivity by the majority of the levels led us to reconsider our initial assignment for the reaction with the nitrone derived from piperidine, which resulted in the discovery of an interesting case of conformational dynamics. [ABSTRACT FROM AUTHOR]

A series of levoglucosenone‐derived thiosemicarbazones have been designed and synthesized following a simple and straightforward procedure. The in vitro antimycobacterial activity of the full library were evaluated against M. tuberculosis H37Ra, with 4 compounds being active in the 1.9–10.7 μg/mL concentration range. To determine the influence of the thiosemicarbazone fragment, the synthetic precursors were analyzed, as well as 50 structurally diverse triazoles and isoxazoles derived from levoglucosenone. Comparing the observed activities with the levels of cell viability in L929 cells at the MIC, it can be concluded that the derivatives reported in this work represent interesting candidates for further development of promising antituberculosis agents. [ABSTRACT FROM AUTHOR]

The use of quantum‐based NMR methods to complement and guide the connectivity and stereochemical assignment of natural and unnatural products has grown enormously. One of the unsolved problems is related to the improper calculation of the conformational landscape of flexible molecules that have functional groups capable of generating a complex network of intramolecular H‐bonding (IHB) interactions. Here the authors present MESSI (Multi‐Ensemble Strategy for Structural Identification), a method inspired by the wisdom of the crowd theory that breaks with the traditional mono‐ensemble approach. By including independent mappings of selected artificially manipulated ensembles, MESSI greatly improves the sense of the assignment by neutralizing potential energy biases. [ABSTRACT FROM AUTHOR]

A straightforward synthesis of a highly substituted biomass‐derived chiral pyrrolidine conveniently functionalized to obtain macrocycles through intramolecular "click" reactions is reported. The experimental difficulties encountered during the macrocyclization stage led us to conduct an extensive DFT study to understand the origins of the findings. The results suggest that the improper conformational landscape of the reactant precludes the pre‐organization required to connect the reactive moieties. We propose that the cumulative Boltzmann amplitudes of reactive conformations (CBAR) prove to be a simple and useful parameter to predict the success or failure of related transformations. [ABSTRACT FROM AUTHOR]

This article, published in the European Journal of Organic Chemistry, discusses the synthesis of cyclic nitronates using nitroalkenes derived from carbohydrates and cyclopentadiene. The authors conducted an experimental study and used DFT calculations to support their findings. The resulting cyclic nitronates were enantiomerically pure and chemically stable. For more information, readers can refer to the research article by M.I. Mangione and co-workers. [Extracted from the article]

A novel BOPHY–fullerene C60 dyad (BP‐C60) was designed as a heavy‐atom‐free photosensitizer (PS) with potential uses in photodynamic treatment and reactive oxygen species (ROS)‐mediated applications. BP‐C60 consists of a BOPHY fluorophore covalently attached to a C60 moiety through a pyrrolidine ring. The BOPHY core works as a visible‐light‐harvesting antenna, while the fullerene C60 subunit elicits the photodynamic action. This fluorophore–fullerene cycloadduct, obtained by a straightforward synthetic route, was fully characterized and compared with its individual counterparts. The restricted rotation around the single bond connecting the BOPHY and pyrrolidine moieties led to the formation of two atropisomers. Spectroscopic, electrochemical, and computational studies disclose an efficient photoinduced energy/electron transfer process from BOPHY to fullerene C60. Photodynamic studies indicate that BP‐C60 produces ROS by both photomechanisms (type I and type II). Moreover, the dyad exhibits higher ROS production efficiency than its individual constitutional components. Preliminary screening of photodynamic inactivation on bacteria models (Staphylococcus aureus and Escherichia coli) demonstrated the ability of this dyad to be used as a heavy‐atom‐free PS. To the best of our knowledge, this is the first time that not only a BOPHY–fullerene C60 dyad is reported, but also that a BOPHY derivative is applied to photoinactivate microorganisms. This study lays the foundations for the development of new BOPHY‐based PSs with plausible applications in the medical field. [ABSTRACT FROM AUTHOR]

A sterereospecific and efficient synthesis of thiosugars derived from levoglucosenone and methyl α‐d‐glucopyranoside was developed by a domino epoxide ring opening‐ xanthate migration to afford 1,3‐oxathiolane‐2‐thiones in high yields. The stereochemical outcome of the new C–S bond was defined by the configuration of the starting materials. The 1,3‐oxathiolane‐2‐thiones were subsequently submitted to a second tandem reaction affording the corresponding 2,3‐episulfide alcohols. The thiosugars obtained are useful building blocks for the synthesis of thiooligosaccharides with potential biological properties. A stereospecific and efficient synthesis of thiosugars derived from levoglucosenone and methyl α‐d‐glucopyranoside was developed by a domino epoxide ring opening‐ xanthate migration to afford 1,3‐oxathiolane‐2‐thiones in high yields. [ABSTRACT FROM AUTHOR]

Abstract: A novel chlorin derivative (TPCF20‐NMe2) has been synthesized as a syn adduct of a pyrrolidine‐fused chlorin bearing a C‐linked N,N‐dimethylaminophenyl residue. The absorption spectrum of TPCF20‐NMe2 is essentially identical to that of TPCF20 in N,N‐dimethylformamide, indicating a very weak interaction between the chlorin macrocycle and the amine group in the ground state. However, the fluorescence emission of the chlorin moiety in TPCF20‐NMe2 is effectively quenched by the attached amine unit. Moreover, TPCF20‐NMe2 is unable to attain a triplet excited state or to photosensitize singlet molecular oxygen. Spectroscopic and redox properties indicate that intramolecular photoinduced electron transfer can take place from the N,N‐dimethylaminophenyl group to the chlorin macrocycle. Thus, in an acid medium, protonation of the amino group leads to a considerable increase in the fluorescence emission, triplet excited‐state formation, and singlet molecular oxygen production. Photodynamic inactivation of Escherichia coli sensitized by TPCF20‐NMe2 is negligible at neutral pH. However, this chlorin becomes highly effective in inactivating E. coli cells under acidic conditions. Therefore, these results indicate that TPCF20‐NMe2 is an interesting molecular structure, in which protonation of the amino group can be used as an off/on molecular switch activating red fluorescence emission and photodynamic activity capable of eradicating bacteria. [ABSTRACT FROM AUTHOR]

The need to find sustainable alternatives to reduce the dependence on fossil sources has led to significant research efforts on the conversion of biomass into platform chemicals. Modern organic chemistry requires easily obtainable chiral building blocks that show high chemical versatility for their application in the synthesis of enantiopure compounds. The selective pyrolytic conversion of cellulose or cellulose-containing materials produces levoglucosenone, a highly functionalized chiral structure. This compound has been innovatively used as a template for the synthesis of key intermediates of biologically active products and for the preparation of chiral auxiliaries, catalysts, and organocatalysts for their application in asymmetric synthesis. [ABSTRACT FROM AUTHOR]

The calculations of NMR properties of molecules using quantum chemical methods have deeply impacted several branches of organic chemistry. They are particularly important in structural or stereochemical assignments of organic compounds, with implications in total synthesis, stereoselective reactions, and natural products chemistry. In studying the evolution of the strategies developed to support (or reject) a structural proposal, it becomes clear that the most effective and accurate ones involve sophisticated procedures to correlate experimental and computational data. Owing to their relatively high mathematical complexity, such calculations (CP3, DP4, ANN-PRA) are often carried out using additional computational resources provided by the authors (such as applets or Excel files). This Minireview will cover the state-of-the-art of these toolboxes in the assignment of organic molecules, including mathematical definitions, updates, and discussion of relevant examples. [ABSTRACT FROM AUTHOR]

In fact, the ability of machine learning strategies to emulate NMR properties at almost the level of DFT accuracy but at much lower computational cost seems to have opened a Pandora's box within the field. We are glad to offer 13 contributions including original research articles, reviews and mini-reviews, highlighting the power of quantum chemistry and machine learning in the field of NMR. [Extracted from the article]

The Cover Feature shows a stunning event that takes place every few years in Patagonia, Argentina: the breaking of the Perito Moreno glacier. Such impressive spectacle is triggered by the pressure developed by the glacier, pushing water through the glacier tunnels underneath, which eventually causes tunnel growing and finally a dramatic collapse as the barrier breaks. In the same way, an interesting domino process towards useful thiosugars is initiated by the strain release involved in epoxide opening. More information can be found in the Full Paper by R. A. Spanevello et al. [ABSTRACT FROM AUTHOR]

Review: [35 refs. [ABSTRACT FROM AUTHOR]

The first application of levoglucosenone-derived chiral auxiliaries in asymmetric 1,3-dipolar cycloaddition reactions of azomethine ylides is given. [ABSTRACT FROM AUTHOR]