Bifunctional Azido(thio)ureas from an -Protected 2-Amino-2-deoxy-d-glucopyranose: Synthesis and Structural Analyses.

This publication reports a facile and convenient preparation of tri--acetyl-glucopyranoses, derived from the corresponding 2-deoxyaminosugar, where the vicinal anomeric and C2 positions are decorated by azido and (thio)ureido groups, respectively. This double functionalization leads to an inherently chiral core incorporating the versatile azido and (thio)ureido linkages prone to further manipulation. The latter also provides a structural element for hydrogen-bonded donor-acceptor (HB-DA) sites, which are of immense value in organocatalytic pursuits.

Exploring and Re-Assessing Reverse Anomeric Effect in 2-Iminoaldoses Derived from Mono- and Polynuclear Aromatic Aldehydes.

A curious and noticeable structural feature in Schiff bases from 2-aminoaldoses is the fact that imino tautomers arranged equatorially in the most stable ring conformation exhibit a counterintuitive reverse anomeric effect (RAE) in the mutarotational equilibrium, i.e., the most stable and abundant anomer is the equatorial one (β).

A True Reverse Anomeric Effect Does Exist After All: A Hydrogen Bonding Stereocontrolling Effect in 2-Iminoaldoses.

The reverse anomeric effect is usually associated with the equatorial preference of nitrogen substituents at the anomeric center. Once postulated as another anomeric effect with explanations ranging from electrostatic interactions to delocalization effects, it is now firmly considered to be essentially steric in nature. Through an extensive research on aryl imines from 2-amino-2-deoxyaldoses, spanning nearly two decades, we realized that such substances often show an anomalous anomeric behavior that cannot easily be rationalized on the basis of purely steric grounds.

From Potential Prebiotic Synthons to Useful Chiral Scaffolds: A Synthetic and Structural Reinvestigation of 2-Amino-Aldononitriles.

This paper explores and revisits in detail the formation and characterization of sugar-based aminonitriles, whose ultimate origin can be traced to the interaction of biomolecules with cyanide. Although the synthesis and spectroscopic data of 2-amino-aldononitriles were reported long ago, there are both contradictory and confusing results among the published data. We have now addressed this concern through an exhaustive structural elucidation of acylated 2-amino- and 2-alkyl(aryl)amino-2-deoxyaldonitriles using mass spectrometry and FT-IR, FT-Raman, and NMR spectroscopies.

Schiff Bases and Stereocontrolled Formation of Fused 1,3-Oxazolidines from 1-Amino-2-Indanol: A Systematic Study on Structure and Mechanism.

This paper thoroughly explores the formation of Schiff bases derived from salicylaldehydes and a conformationally restricted amino alcohol (1-amino-2-indanol), as well as the generation of 1,3-oxazolidines, a key heterocyclic core present in numerous bioactive compounds. We provide enough evidences, both experimental-including crystallographic analyses and DFT-based calculations on imine/enamine tautomerism in the solid state and solution. In the course of imine formation, a pentacyclic oxazolidine-oxazine structure could be isolated with complete stereocontrol, whose configuration has been determined by merging theory and experiment.

Unpacking the Drivers of LGBT+ Legislation.

This paper stems from the hypothesis that there are various key factors rooted in economic, political, and social grounds which actively influence and determine the adoption and evolution of LGBT+ rights in the legal framework of any country. The goal of this research is to analyze these factors and understand how they channel the LGBT+ legislation in our present world. Assuming there is an asymmetry in this application and by extension in LGBT+ individuals' human rights, which are often ignored if not deprived in many parts of the world, this study seeks to understand the reasons behind that asymmetry.

A synthetically benign one-pot construction of enamino-xanthene dyes.

Polyhydroxylated phenols are components of biomass and precursors of pigments in plants. This paper reports a novel entry to xanthene dyes, involving the reaction of 2,4,6-trihydroxybenzaldehyde with primary aliphatic amines. This catalyst-free synthesis exhibits a high atom economy and can be conducted under eco-friendly conditions and operational simplicity.

Expanding amphiphilic architectures by ring-opening of epoxides and polyepoxides with N-methyl-d-glucamine: Structure, chiral bias and gelation.

The facile reaction of a readily available aminopolyol from the chiral pool, N-methyl-d-glucamine, which avoids the side reactions usually associated to anomers of amino sugars, with epoxide and polyepoxide derivatives, enables the preparation of new non-ionic surfactant-like structures combining hydrophilic and hydrophobic moieties. The molecular architectures thus obtained range from linear to tripodal and pyramidal structures. The resulting substances containing multiple chiral centers exist as diastereomeric mixtures, for which various conformations are likewise possible by virtue of inter-chain interactions.

Imine or Enamine? Insights and Predictive Guidelines from the Electronic Effect of Substituents in H-Bonded Salicylimines.

Imine and enamine bonds decorate the skeleton of numerous reagents, catalysts, and organic materials. However, it is difficult to isolate at will a single tautomer, as dynamic equilibria occur easily, even in the solid state, and are sensitive to electronic and steric effect, including π-conjugation and H-bonding. Here, using as model Schiff bases generated from salicylaldehydes and TRIS in a set of linear free energy relationships (LFER), we disclose how the formation of either imines or enamines can be controlled and provide a comprehensive framework that captures the structural underpinning of this prediction.

Electronic effects in tautomeric equilibria: the case of chiral imines from d-glucamine and 2-hydroxyacetophenones.

A one-pot procedure for preparing a series of chiral imines by direct condensation of d-glucamine with 2-hydroxyacetophenones is described. Under conventional acetylation an unexpected mixture of two different peracetylated molecules is obtained, one with an open enamine structure, and the other incorporating an N-acetyl-1,3-oxazolidine into the acyclic skeleton. Surprisingly, both molecules coexist within the crystal's unit cell, as inferred from single-crystal X-ray analysis of a 5-bromo-substituted aryl derivative.

Tautomerism and stereodynamics in Schiff bases from gossypol and hemigossypol with N-aminoheterocycles.

Tautomerism plays a pivotal role in structural stabilization and reactivity. Herein we investigate in detail, aided by DFT simulations, the case of gossypol, a naturally occurring atropisomeric dialdehyde showing promising properties as a male contraceptive and an antineoplasic agent. Its toxicity linked to reactive aldehydo groups can be reduced through amino conjugation.

Implementation of a Competency-based Pressure Ulcer Curriculum for Medical Students: Outcomes from an Educational Intervention Study.

Unlabelled: A paucity of research exists on medical student pressure ulcer education.

Purpose: This study examines medical student competency outcomes following implementation of a competency-based curriculum that included a pressure ulcer component in its educational intervention.

Methods: Over a 5-year period, 645 medical students completed the curriculum, which included a preceptor-led didactic session, online study resources, clinical experiences, and a brief online competency assessment.

Prebiotic-Like Condensations of Cyanamide and Glyoxal: Revisiting Intractable Biotars.

We report a detailed investigation into the nature of products that are generated by the reactions of cyanamide and glyoxal, two small molecules of astrochemical and prebiotic significance, under different experimental conditions. The experimental data suggest that the formation of oligomeric structures is related in part to the formation of insoluble tholins in the presence of oxygen-containing molecules. Although oligomerization proceeds well in water, product isolation turned out to be impractical.

On the Plausibility of Pseudosugar Formation in Cometary Ices and Oxygen-rich Tholins.

We revisit herein the formation and structure of dihydroxy dioxanes, which can be obtained from prebiotically available precursors and can be regarded as primeval sugar surrogates. Previous studies dealing with the heterogeneous composition of interstellar bodies point to the existence of significant amounts of small polyalcohols along with oxygen-containing oligomers. Even though such derivatives did not give rise to nucleosides and oligonucleotides, nor they were incorporated into subsequent metabolic routes, molecular chimeras based on sugar-like species could be opportunistic scaffolds in pre-evolutionary scenarios.

Rethinking aromaticity in H-bonded systems. Caveats for transition structures involving hydrogen transfer and π-delocalization.

Monoaza- and diaza-derivatives of malondialdehydes, in short aminoacroleins and vinamidines, are prototypical examples of open-chain structures prone to π-electron delocalization, for which intramolecular hydrogen bonding enhances (or diminishes) their pseudoaromaticity depending on the substitution pattern. This interplay is illustrated herein by DFT-based calculations of aromaticity indices in the gas phase and polar solvents. Elucidation of transition structures involved in tautomeric conversions helps to solve how the intramolecular hydrogen transfer occurs.

Pseudo-cyclic structures of mono- and di-azaderivatives of malondialdehydes. Synthesis and conformational disentanglement by computational analyses.

Mono- and diaza-derivatives of malondialdehydes, namely 3-alkyl(aryl)amino-2-arylacroleins and 1,5-dialkyl(aryl)-3-arylvinamidines are open-chain systems in which extended electron delocalization and pseudoaromaticity can be envisaged. A set of diversely functionalized compounds has been synthesized and characterized by spectroscopic data and X-ray diffractometry. Quantum-chemical calculations were performed for all possible neutral tautomers and conformers in the gas phase and compared to those in polar solvents (CHCl3, DMSO, and EtOH) at the M06-2X/6-311++G(d,p) level.

Stepwise formation of 1,3-diazolium-4-thiolates by münchnone cycloadditions: promising candidates for nonlinear optics.

An improved preparation of mesoionic heterocycles 1,3-diazolium-4-thiolates by [3 + 2] cycloadditions of münchnones with aryl isothiocyanates is reported. The process takes place with high or complete regioselectivity, and fast and clean transformations are observed under microwave heating in DMF. DFT calculations support that this cycloaddition proceeds preferably through a stepwise mechanism.

On the prebiotic synthesis of D-sugars catalyzed by L-peptides: assessments from first-principles calculations.

What accounts for a particular chiral selection in the case of a few sugars of prebiotic relevance, thereby mirroring the asymmetry observed in nature? By using first-principles calculations, the generation of pentoses from glycolaldehyde (the initial product of the autocatalytic formose reaction), which has been detected in outer space), has been modeled by using L-Val-L-Val as a primeval catalyst. Our theoretical study provides insight into the mechanism of this reaction and satisfactorily explains a few key molecular events. Our rationale agrees with the reported experimental data and shows that the D-configuration is only favored for ribose.

Tautomerism in Schiff bases. The cases of 2-hydroxy-1-naphthaldehyde and 1-hydroxy-2-naphthaldehyde investigated in solution and the solid state.

Schiff bases derived from hydroxyl naphthaldehydes and o-substituted anilines have been prepared and their tautomerism assessed by spectroscopic, crystallographic, and computational methods. Tautomeric equilibria have also been studied and reveal in most cases a slight preference of imine tautomers in solution; a fact supported by DFT calculations in the gas phase as well as incorporating solvent effects through the SMD model. To simulate the effect exerted by the crystal lattice on tautomer stability, we have developed a computational protocol in the case of 1-tert-butyl-2-(2-hydroxy-1-naphthylmethylene)aminobenzene whose data have been obtained experimentally at 120 K.

On the enhanced reactivity and selectivity of triazole formation in molecular flasks. A theoretical rationale.

The azide-alkyne cycloaddition assisted by a self-assembled molecular flask developed by Rebek and coworkers (Org. Lett., 2002, 4, 327) has been simulated by means of the ONIOM methodology, thereby evidencing the reliability of this theoretical approach to model such large encapsulated systems.

A quantitative structure-reactivity relationship in N-acetyl oxazolidines: an electrostatic interaction controls rotamer population.

The conformational population of Z and E isomers of the amide bond in N-acetyl oxazolidines is dictated by the electronic nature of the vicinal aryl ring. Experimental and theoretical data support a rationale based on a strong and stereodirecting charge-charge interaction that should be added to the arsenal of non-covalent interactions and whose influence can be more important than once thought.

Assessing the whole range of CuAAC mechanisms by DFT calculations--on the intermediacy of copper acetylides.

The archetypal Cu(I)-catalyzed alkyne-azide click cycloaddition (CuAAC) has been explored thoroughly via density functional calculations, modeling copper nuclei with the LANL2DZ basis set and aqueous environments with CPCM solvation. All the mechanistic proposals, ranging from the intermediacy of copper acetylides to π-complexes and multinuclear clusters have been compared. The known features of the CuAAC reaction such as the observed second order kinetics for the Cu(I) species and the marked regioselectivity have been taken into account.

Push-pull 1,3-thiazolium-5-thiolates. Formation via concerted and stepwise pathways, and theoretical evaluation of NLO properties.

The transformation of münchnones (mesoionic rings featuring the 1,3-oxazolium-5-olate core) into their sulfur counterparts (1,3-thiazolium-5-thiolates) by reaction with CS(2), pioneered by Huisgen and his group in the early 1970s, has been re-investigated in detail by means of both experimental and theoretical methods. The synthetic strategy can be tuned to incorporate donor and acceptor groups in appropriate positions. Calculations of molecular hyperpolarizabilities together with orbital topologies evidence that these sulfur-containing heterocycles exhibit nonlinear optical responses, thereby pointing to potential applications of mesoionic structures in the NLO field.

Unusual aryl migration in a mesomeric betaine in the solid and liquid state: mechanistic insights into the SNAr reaction.

An intramolecular S(N)Ar mechanism has been identified in the unexpected aryl migration observed in a mesomeric betaine. The process changes drastically the optical and spectroscopic properties and should be a valuable model for related heteroaromatic systems.

A new model for mapping the peptide backbone: predicting proton chemical shifts in proteins.

This paper describes a methodology that correlates experimental chemical shifts (at the alpha proton) of proteins with their geometrical data (both dihedral angles and distances) obtained from 13 representative proteins, which are taken from the Protein Data Bank (PDB) and the BioMagRes Data Bank (BMRB). To this end, the experimentally measured proton chemical shifts of simple amides have been correlated with DFT-based calculated structures, at the B3PW91/6-31G* level. This results in a series of mathematical relationships, which are extrapolated to the above-mentioned proteins giving rise to a modified equation for such skeleta.