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Chiral γ-nitroaldehydes 1 are easily accessible by the organocatalytic Michael addition of aldehydes to nitroalkenes. In this paper, we report the organocatalytic fluorination of 1 with N-fluorobenzenesulfonimide (NFSI) leading to the highly stereoselective construction of a challenging quaternary fluorinated stereocenter at the α position of α,α-dialkyl aldehydes. The reaction takes place via a chiral trisubstituted enamine, so far rather unexplored in the field of organocatalysis. Fluorinated products 3 are direct precursors of chiral monofluorinated 3,4-polysubstituted pyrrolidines. Mechanistic details are discussed with the aid of computational results.

The invention relates to thermochemiluminescent silica nanoparticles containing in dispersion in the silica matrix molecules of a thermochemiluminescent acridine-based 1,2-dioxetane and additional chemical species, such as a fluorescent energy acceptor with the function of improving the efficiency of the thermochemiluminescent reaction and/or modifying the emission wavelength, and a method for the synthesis thereof. The nanoparticles are functionalized on the surface with reactive groups (e.g. amines) and procedures are described for bonding them to biospecific probes (e.g. antibodies) and enabling their use as thermochemiluminescent markers in bioanalytical methods (e.g. immunometric methods) based on thermochemi luminescence measurements.

Bicyclic silyl ether derivatives 1, which are derived from simple chemical manipulations of trans-4-L-hydroxyproline, were recently proposed, by us, as conformationally constrained analogues of Jørgensen–Hayashi’s catalysts 2. Despite the structural similarities, 1 displays remarkable performance in iminium chemistry with respect to 2, but much lower reactivity in enamine chemistry. The peculiar structural features of 1 confer a pattern of reactivity between Jørgensen–Hayashi’s catalysts and MacMillan’s imidazolidinones.

We recently proposed 3-methoxy-4-methoxycarbonyl-1,2-dioxanes 3 as promising scaffolds enabling access to potential antimalarial drugs. We present here an optimized two-step synthesis of 3 characterized by high yields, simple work-up procedures and high diastereoselectivity allowing us to readily prepare 3 on multigram scale. The versatility of the 1,2- dioxane scaffold was demonstrated by our generation of a new family of 1,2-dioxane-4-carboxamides 8a–h and the realization of their in vitro activities against chloroquine-sensitive (D10) and chloroquine-resistant (W2) P. falciparum strains. In particular, one of these amides (8e), displayed antimalarial activity on par with the natural product lead plakortin and was 5-fold more active than its methyl ester analogue 3. Structure–activity relationship (SAR) analysis supported by DFT calculations revealed that, for this family of compounds, alkyl substituents at C6 dictate, in large part, the degree of antimalarial activity. This finding contrasts those previously observed for the ester series.

Although magnesium is essential for a number of cellular processes such as proliferation and death, its distribution and intracellular compartmentalization have not yet been thoroughly elucidated, mainly because of the inadequacy of the available techniques to map intracellular magnesium distribution. For this reason, particular interest has been recently demonstrated by a family of fluorescent molecules, the DCHQ series (Diaza-18-Crown-16 8-Hydroxyquinoline), that have shown an affinity and specificity for magnesium higher than all the other commercial probes, thus permitting the detection of the total intracellular magnesium [1]. The synthesis of the DCHQ compounds has been optimized by using microwave heating [2]: this approach allowed us to easily modify the basic structure with the introduction of various functional groups to obtain a number of derivatives with improved features of fluorescence, uptake and localization with respect to the original compound (DCHQ1). Fluorescence quantum yield has been enhanced via introduction of aromatic side groups (DCHQ7 and 13), that contemporary conferred improved features of uptake, since the probes are highly retained inside the cells after washings. Enhanced uptake has also been achieved with DCHQ12, a DCHQ-AM derivative that is recognized by the intracellular esterases. DCHQ11, with two long hydrophobic side chains, instead, allowed a better staining of the membranes due to its high affinity to the lipophilic environments. Results show the potentiality of these new fluorescent probes in providing novel insight in the study of intracellular magnesium homeostasis.