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Aziridines, the nitrogen counterparts of epoxides, are among the most challenging and intriguing heterocycles in organic chemistry since they not only represent the endpoints of several total syntheses as common scaffolds in natural products but also act as crucial precursors of complex molecules. The present review provides a brief overview of aziridine derivatives as well as the authors’ choice of published papers that highlight recent enhancements concerning asymmetric organocatalytic strategies involved in aziridination reactions.

We employed the membrane of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) liposomes suspended in water as a microenvironment for carrying out the organocatalytic epoxidation of an α-alkylidene oxindole. The reaction proceeds smoothly and displays diastereo- and enantio-selectivity that differs from what is achieved under bulk solution conditions. The potential of organocatalytic approaches for synthetic transformations in aqueous phase in the presence of dispersed membranes is briefly discussed.

Taking into account the postulated reaction mechanism for the organocatalytic epoxidation of electron-poor olefins developed by our laboratory, we have investigated the key factors able to positively influence the H-bond network installed inside the substrate/catalyst/oxidizing agent. With this aim, we have: (i) tested a few catalysts displaying various effects that noticeably differ in terms of steric hindrance and electron demand; (ii) employed alpha-alkylidene oxindoles decorated with different substituents on the aromatic ring (11a-“g), the exocyclic double bond (11h-l), and the amide moiety (11m-“v). The observed results suggest that the modification of the electron-withdrawing group (EWG) weakly conditions the overall outcomes, and conversely a strong influence is unambiguously ascribable to either the N-protected or N-protected lactam framework. Specifically, when the NH free substrates (11m-“u) are employed, an inversion of the stereochemical control is observed, while the introduction of a Boc protecting group affords the desired product 12v in excellent enantioselectivity (97:3 er).

The present work aimed to synthesise promising antioxidant compounds as a valuable alternative to the currently expensive and easily degradable molecules that are employed as stabilizers in industrial preparation. Taking into account our experience concerning domino Friedel-Crafts/lactonization reactions, we successfully improved and extended the previously reported methodology toward the synthesis of 3,3-disubstituted-3H-benzofuran-2-one derivatives 9–20 starting from polyphenols 1–6 as substrates and either diethylketomalonate (7) or 3,3,3-trifluoromethyl pyruvate (8) as electrophilic counterpart. The antioxidant capacity of the most stable compounds (9–11 and 15–20) was evaluated by both DPPH assay and Cyclic Voltammetry analyses performed in alcoholic media (methanol) as well as in aprotic solvent (acetonitrile). By comparing the recorded experimental data, a remarkable activity can be attributed to few of the tested lactones.

Glaucoma affects millions of people worldwide, causing optic nerve damage and blindness. The elevation of the intraocular pressure (IOP) is the main risk factor associated with this pathology, and nowadays, the key therapeutic target of the existing pharmacological treatments. We studied, as potential ocular hypotensive agents, compounds acting on two receptors (serotonin 2A, 5-HT2A, and adrenergic ?1) linked to the regulation of the humour aqueous dynamic. In this article we describe the design, synthesis, and pharmacological profiling of a series of novel bicyclic and tricyclic 2N-alkyl-indazole-amide derivatives. The work brought to the identification of compound 28, a 3,4-dihydropyrazino[1,2-b]indazol- 1(2H)-one derivative, with potent 5-HT2A antagonism, >100 fold selectivity over other serotonin subtype receptors and high affinity for the ?1 receptor. Moreover, when administered locally, 28 showed superior ocular hypotensive action in vivo, compared to the clinically used reference compound timolol.

International audience; An asymmetric domino Friedel–Crafts/lactonization sequence between phenols and trifluoropyruvatehas been accomplished for the first enantioselective synthesis of (S)-BHFF, a positive allosteric modulator(PAM) of GABAB receptor. The developed protocol leads to 3-OH-benzofuranone derivatives bearing aquaternary stereogenic center, and gives a valuable access to bioactive compounds with promising pharmaceuticalapplications

International audience; The ubiquitous presence of spirooxindole architectures with several functionalities and stereogenic centers in bioactive molecules has been appealing for the development of novel methodologies seeking their preparation in high yields and selectivities. Expansion and refinement in the field of asymmetric organocatalysis have made possible the development of straightforward strategies that address these two requisites. In this review, we illustrate the current state-of-the-art in the field of spirooxindole synthesis through the use of non-covalent organocatalysis. We aim to provide a concise overview of very recent methods that allow to the isolation of unique, densely and diversified spirocyclic oxindole derivatives with high structural diversity via the use of cascade, tandem and domino processes.