Daniela Imperio

Despite being discovered over a century ago, lathyrane diterpenoids have only recently attracted significant attention from the organic chemistry community due to their distinctive carbon framework, characterized by a 5/11/3 tricyclic system. The conformational rigidity of these scaffolds promotes close spatial proximity between functional groups, making transannular reactions a powerful tool for the construction of new complex polycyclic architectures. In parallel, compounds from the genus Euphorbia have emerged as versatile molecular frameworks in medicinal chemistry, exhibiting a wide range of biological activities, including cytotoxic, antiviral, and neuroprotective effects. This review summarizes recent advances in the field, with particular emphasis on synthetic strategies, structural diversity, and medicinal chemistry aspects of this intriguing class of secondary metabolites.

Despite being discovered over a century ago, lathyrane diterpenoids have only recently attracted significant attention from the organic chemistry community due to their distinctive carbon framework, characterized by a 5/11/3 tricyclic system. The conformational rigidity of these scaffolds promotes close spatial proximity between functional groups, making transannular reactions a powerful tool for the construction of new complex polycyclic architectures. In parallel, compounds from the genus Euphorbia have emerged as privileged scaffolds in medicinal chemistry, exhibiting a wide range of biological activities, including cytotoxic, antiviral, and neuroprotective effects. This review summarizes recent advances in the field, with particular emphasis on synthetic strategies, structural diversity, and medicinal chemistry aspects of this intriguing class of secondary metabolites.

Despite nearly two centuries of investigation, the photochemistry of α‐santonin continues to reveal unexpected reactivity. In this study, we systematically explored the behavior of α‐santonin under UVC (254 nm) and UVA (390 and 456 nm) irradiation in protic and aprotic solvents, uncovering a marked dependence of product distribution on both irradiation wavelength and solvent environment. While irradiation at 254 nm in aprotic solvents selectively afforded lumi ‐santonin ( 1 ), irradiation at 390 nm promoted further rearrangement to mazdasantonin ( 4 ). In protic media, solvent polarity and steric hindrance strongly influenced the reaction outcome, leading to photosantonic acid esters and lactone derivatives. Notably, irradiation in secondary and tertiary alcohols at 390 nm provided two previously undescribed lumi ‐derivatives. Mechanistic investigations suggest the involvement of competing diradical and zwitterionic pathways. These results demonstrate that modern wavelength‐controlled photochemistry can still uncover unexplored transformations even within classical photochemical systems such as α‐santonin.

Organotrifluoroborates are an important functional group that is used in synthesis, diagnostics, and, more recently, in theranostics. Here, we present a practical, one‐step synthesis of ammonium and sulfonium trifluoroborate zwitterionic derivatives by N‐ or S‐ alkylation of bromomethyltrifluoroborate. The reaction proceeds smoothly to produce the desired compounds with good to excellent yields. In particular, the preparation of some sulfonium trifluoroborate derivatives, which avoids the use of expensive or troublesome reagents, their complete spectroscopic characterization, and an example of their application in a click‐chemistry reaction are reported.

Gossypol, a major metabolite of cotton plants, has been used for the first time as a source material for the preparation of derivatives employed in asymmetric catalysis. Specifically, the (R)‐enantiomer of the 6,6’,7,7’‐O‐tetramethyl derivative of apogossypol has been synthesized in five steps and 47% total yield from enantiopure (‒)‐(R)‐gossypol. This axially chiral diol was used as a ligand in the enantioselective boron‐catalyzed Diels–Alder reactions of 2’‐hydroxychalcones and dienes, achieving high yields and moderate enantioselectivities. Considering the potentially high amounts of gossypol isolable from agricultural wastes of cotton crops, these results open the way for the introduction of a promising new class of biomass‐derived asymmetric catalysts.

Boron neutron capture therapy (BNCT) is an oncological treatment based on the neutron capture reaction on ¹⁰B. The only two compounds approved for phase I/II clinical trials are sodium borocaptate (BSH) and 4-boronophenylalanine (BPA). While BPA has been widely exploited in clinical trials, the use of BSH is limited due to its insufficient uptake by tumor cells. Herein, we report a novel formulation based on silk fibroin nanoparticles (SFNs), capable of loading a large amount of borocaptate ions. The nanoparticles have been characterized and tested on U87 glioma cells, and boron uptake was measured using neutron autoradiography, which involved irradiating the samples in a thermal neutron field. Measurements demonstrated the crucial role of the nanocarrier in enhancing boron internalization. Notably, SFNs-BSH achieved 29.5 ppm total boron uptake in U87 cells – comparable to clinical BPA – at 4× lower dose.

The possibility of duplicating the efficiency and selectivity of natural processes under laboratory conditions remains a significant challenge for organic chemists. In this letter, we demonstrated that it is possible to introduce pinpoint modifications and to reshape the terpene skeleton of easily available oleananes in a biomimetic fashion. Furthermore, aromatization of the A ring of the triterpene system is reported here for the first time, mimicking what occurs exclusively in nature in sediments.

Background: Boron Neutron Capture Therapy (BNCT) is a promising cancer treatment that combines tumor-selective boron delivery agents with thermal neutrons to kill cancer cells while sparing normal tissue. BNCT requires boron-containing compounds that exhibit high tumor selectivity and achieve therapeutic boron concentrations within tumor cells. This work focuses on the early development of a novel boron cluster carbohydrate derivative based on the glucosamine structure. Our results indicate that this derivative may have advantages over the typical boron delivery agent used in clinical applications and may significantly improve boron delivery capacity at the cellular level. Methods: The performance of the compound in terms of boron uptake was tested in the U87-MG glioblastoma cell line employing neutron autoradiography imaging and quantification. Results: The compound was non-toxic for cells, and it showed a remarkable capacity to enrich cells with boron. The ratio between boron concentration provided in the culture medium and boron concentration achieved in cells was compared to that obtained with boronophenylalanine (BPA), the gold standard in BNCT. The result demonstrated a significantly better performance compared with BPA, showing that the novel agent can concentrate boron in cells more than in culture medium. Conclusions: The encouraging preliminary results provide a starting point for its potential application in in vivo tests.

Asymmetric epoxidation represents a hot topic in organic synthesis. In recent years, organocatalysts based on sugar skeletons have been exploited in asymmetric epoxidation to achieve enantiomeric pure epoxides. In this work, two different endocyclic ketones derived from glucose and galactose protected with a 4,6-O-benzylidene group have been prepared and exploited for Shi-type epoxidation. The two carbohydrates show an opposite preferential stereoselective epoxidation on various olefins, affording the epoxides in high conversions and modest enantioselectivities. DFT calculations disclosed the reasons behind the inversion of selectivity achieved by the two catalysts, showing that a delicate balance between the catalyst conformation, its protecting groups, and the secondary interactions with the substrate govern the final observed results.