Lucio Toma

Ring puckering is a central conformational phenomenon that strongly influences the structure and reactivity of cyclic and heterocyclic molecules, with particular relevance to carbohydrate chemistry and stereoelectronic effects. Ring puckering represents a critical conformational phenomenon in organic chemistry, where cyclic molecules deviate from planarity through out‐of‐plane bending motions to minimize steric and electronic strain. To make quantitative puckering analysis more accessible, this work presents a free, open‐source Python tool that computes Cremer–Pople puckering parameters for five‐, six‐ and seven‐membered rings from standard .xyz coordinates and produces intuitive two‐dimensional visualizations of amplitude and phase. The implementation centers on vectorized projections onto sinusoidal basis functions, special‐case handling for different ring sizes, and interactive selection of ring atoms; it emphasizes clarity, speed, and explicit support for seven‐membered systems often neglected due to the difficulty to represent toroidal landscape. Validation and discussion illustrate how the tool maps canonical envelope, twist, chair, boat, and higher‐dimensional pseudorotation landscapes onto readable plots, enabling rapid classification of conformers and interpretation of dynamical motifs. The program provides a practical and accessible implementation for the analysis and visualization of ring conformations based on puckering coordinates.

Five-membered oxygenated heterocycles, such as substituted tetrahydrofurans (THFs), are important structural motifs in bioactive compounds and can be efficiently accessed through palladium-catalyzed asymmetric allylic alkylation (AAA). In this context, the desymmetrization of mesodiols represents a powerful strategy for the stereocontrolled construction of chiral THF frameworks. Herein, we present a combined experimental and computational study aimed at elucidating the origin of an unusual diastereoselectivity inversion observed in this reaction. While ligands of the Trost family are generally considered interchangeable when sharing the same chiral information, experimental results show that switching between (S,S)-DACH-Ph (L1) and (R,R)-ANDEN-Ph (L2) leads to a reversal of the major diastereomer formed without significant loss of enantioselectivity. Density functional theory (DFT) calculations reveal that this behavior cannot be rationalized by the only classical Trost–Toste steric quadrant model. Instead, the selectivity is governed by a network of ligand-controlled noncovalent interactions, including hydrogen bonding between the ligand amide N–H, the acetate counteranion, and the substrate hydroxyl groups, which dictate the relative stability of the competing transition states. These findings provide a mechanistic framework that explains the observed disaster conversion and highlights the critical role of interaction patterns beyond steric effects, offering new predictive insights for the design of asymmetric AAA processes.

Properly substituted tetrahydrofuran (THF) rings are important building blocks in the synthesis of many natural metabolites. Having reliable procedures to control the stereo-selectivity at the THF core while decorating it with different substituents is a fundamental requirement to achieve and fulfill the complexity of nature. We recently reported a new chemical approach to control the stereochemistry in the alkylation and arylation of furanoside derivatives by using a rhenium(V) complex to form an intermediate oxo-carbenium species able to react with proper soft nucleophiles. Here, we describe theoretical calculations, performed at the DFT B3LYP level, to disclose the important mechanistic features which regulate the entire catalytic cycle of the reaction of mono-and disubstituted furanosides with allyltrimethylsilane catalyzed by Re(O)Cl3(OPPh3)(Me2S). Moreover, the key factors governing the allylation step were investigated, confirming that the stereoselectivity, which is independent of the anomeric configuration of starting acetal, mainly arises from the orientation of the substituent at C-4, with only marginal contribution of the substituent at C-5. Finally, puckering Cremer- Pople parameters were used to take trace of the structural modifications throughout the catalytic cycle.

A chiral organic cage is able to detect the surrogate of ⁹⁹ TcO ₄ ⁻ in water, fruit juice and artificial urine medium.

In this work, the synthesis of the cannabinoid receptor 1 neutral antagonists 8-chloro-1-(2,4-dichlorophenyl)-N-piperidin-1-yl-4,5-dihydrobenzo-1H-6-oxa-cyclohepta[1,2-c]pyrazole-3-carboxamide 1a and its deaza N-cyclohexyl analogue 1b has led to a deepening of the structure-activity studies of this class of compounds. A series of novel 4,5-dihydrobenzo-oxa-cycloheptapyrazoles analogues of 1a,b, derivatives 1c–j, was synthesized, and their affinity towards cannabinoid receptors was determined. Representative terms were evaluated using in vitro tests and isolated organ assays. Among the derivatives, 1d and 1e resulted in the most potent CB₁ receptor ligands (K_iCB₁ = 35 nM and 21.70 nM, respectively). Interestingly, both in vitro tests and isolated organ assays evidenced CB₁ antagonist activity for the majority of the new compounds, excluding compound 1e, which showed a CB₁ partial agonist behaviour. CB₁ antagonist activity of 1b was further confirmed by a mouse gastrointestinal transit assay. Significant activity of the new CB₁ antagonists towards food intake was showed by preliminary acute assays, evidencing the potentiality of these new derivatives in the treatment of obesity.

Herein, we present an example of covalent cages, whose flexible framework undergoes extending–shrinking motion under halide control. In absence of halide anions, the free cage assumes a flattened conformation: the cavity is compressed along the C₃ axis passing through the tertiary amines, and the two tribenzylamine platforms are eclipsed. Halide encapsulation promotes a large conformational rearrangement of the cage, involving an extension of the cavity along the C₃ axis and shrinkage along the equatorial plane. Interestingly, the rearrangement is accompanied by the pyramidal inversion of the tertiary amines, and by the rotation of the tribenzylamine-based platforms, which become staggered. The imidazolium containing arms wrap around the spherical anion, leading to a racemic mixture of the M and P-helical complexes. As expected from the flexible structure of the cage, the switch between the two limit conformations can be repeated for several cycles under alternating chemical stimuli (AgNO₃/TBACl). This result is consistent with the low activation barriers determined by computational investigations. These also allowed us to quantify the energy difference between the shrunk and expanded cage conformations, and to hypothesize an energetic pathway along which the conformational rearrangement can occur.