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Herein we present the biocatalysed preparation of a mono- N -carbamate-protected precursor of antitumoral Nutlin-3a through enantioselective alkoxycarbonylation of meso -1,2-disubstituted-1,2-diaminoethane using enzyme lipases and dialkyl carbonates as acylating agents. A series of supported or free lipase enzymes were screened in combination with commercially available diallyl, diethyl and dimethyl carbonates. The reactions were conducted at different temperatures, for different reaction times and with variable co-solvent systems to evaluate the effects on the enzyme catalytic activity. The best results in terms of conversion, enantiomeric excess and yield were obtained when lipase from Candida antarctica B (CAL-B) was used with diallyl carbonate (DAC) when conducting the reaction solventless at 75 °C., Competing Interests: The authors declare no conflicts of interest.

In the present study, twin-column recycling chromatography has been employed for the purification of a Cannabis extract by using a green solvent, ethanol, as the mobile phase. In particular, the complete removal of the psychoactive tetrahydrocannabinol (THC) from a Cannabis extract rich in cannabidiol (CBD) was achieved under continuous conditions. The performance of the method, in terms of compound purity, recovery, productivity and solvent consumption, was compared to that of traditional batch operations showing the potential of the twin-column recycling approach. The employment of a theoretical model to predict the band profiles of the two compounds during the recycling process has facilitated method development, thus further contributing to process sustainability by avoiding trial and error attempts or at least decreasing the number of steps significantly., (© 2024. The Author(s).)

The existence of slow adsorption-desorption kinetics in chiral liquid chromatography is common knowledge. This may significantly contribute to worsening the efficiency and kinetic performance of a chromatographic run, especially when high flow rates are employed. Many attempts and protocols have been proposed to access this term, the so-called c ads , but they are based on different (theoretical) assumptions. As a consequence, no official method is available for the estimation of the adsorption-desorption kinetics term. In this work, a novel approach to access c ads is presented. This procedure combines experimental results obtained with kinetic and thermodynamic measurements. The investigations have been performed on two zwitterionic teicoplanin chiral stationary phases (CSPs) based on 1.9 μ m fully porous and 2.0 μ m superficially porous particles (FPPs and SPPs), using Z-D,L-Methionine as probe molecule. Kinetic studies have been performed through the combination of both stop-flow and dynamic measurements, while adsorption isotherms have been calculated through Inverse Method. This study has confirmed that, on both particle formats, analyte diffusion on the surface of the particle is negligible, meaning that adsorption is localized, and it has been demonstrated that adsorption-desorption kinetics is strongly dependent on particle geometry and, in particular, on the loading of chiral selector. These findings are fundamental not only to unravel novel aspects of the complex enantiorecognition mechanism but also to optimize the employment of CSPs for ultra-fast and preparative applications., (© 2024. The Author(s).)

Bioactive compounds, including active pharmaceutical ingredients (APIs), are often chiral molecules where stereoisomers have different biological and therapeutic activity. Nevertheless, the preparation of these molecules can lead to racemic or scalemic mixtures (it is not trivial to produce just the optically pure compound). The evaluation of the enantiomeric purity of bioactive compounds, and therefore quality, is indeed of fundamental importance for regulatory scopes. Chiral high performance liquid chromatography (HPLC) is the gold standard technique to separate and to purify enantiomers. This comes from the wide availability of commercial chiral stationary phases (CSPs) and operational modes, which makes the technique extremely versatile. In recent years, the most relevant trend in the field of chiral analytical HPLC has been the development of CSPs suitable for fast or even ultrafast separations, thus favoring the high throughput screening of biologically active chiral compounds. This process has somehow lagged behind compared to achiral HPLC, due to a series of practical and fundamental issues. The experience has shown how in chiral chromatography even very basic concepts, such as the supposed kinetic superiority of core-shell (pellicular) particles over fully porous ones to improve the chromatographic efficiency, cannot be taken for granted. In this review, the most relevant fundamental and practical features that must be taken into consideration to design successful high-throughput, fast enantioseparations will be discussed. Afterwards, the main classes of CSPs and the most relevant, recent (last five-year) high-throughput applications in the field of the separation of chiral bioactive compounds (for pharmaceutical, forensic, food, and omics applications) will be considered., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The enormous influence in terms of bioactivity, affinity, and selectivity represented by the replacement of (L)-2,6-dimethyl tyrosine (Dmt) instead of Phenylalanine (Phe) into Nociceptin/orphanin (N/OFQ) neuropeptide analogues has been well documented in the literature. More recently, the non-natural amino acid (L)-2-methyl tyrosine (Mmt), with steric hindrance included between Tyr and Dmt, has been studied because of the modulation of steric effects in opioid peptide chains. Here, we report a new synthetic strategy to obtain Mmt based on the well-known Pd-catalyzed ortho -C(sp 2 )-H activation approach, because there is a paucity of other synthetic routes in the literature to achieve it. The aim of this work was to force only the mono- ortho -methylation process over the double ortho -methylation one. In this regard, we are pleased to report that the introduction of the dibenzylamine moiety on a Tyr aromatic nucleus is a convenient and traceless solution to achieve such a goal. Interestingly, our method provided the aimed Mmt either as N -Boc or N -Fmoc derivatives ready to be inserted into peptide chains through solid-phase peptide synthesis (SPPS). Importantly, the introduction of Mmt in place of Phe 1 in the sequence of N/OFQ(1-13)-NH 2 was very well tolerated in terms of pharmacological profile and bioactivity.

An increased awareness of diseases associated with Human herpesvirus 6 (HHV-6) infection or reactivation has resulted in a growing interest in the evaluation of the best treatment options available for the clinical management of HHV-6 disease. However, no compound has yet been approved exclusively for HHV-6 infection treatment. For this reason, the identification of anti-HHV6 compounds provides a valuable opportunity for developing efficient antiviral therapies. A possible target for antiviral drugs is the virus-cell fusion step. In this study, we synthetized potential fusion intermediates inhibitors based on the rhodanine structure. The obtained derivatives were tested for cytotoxicity and for antiviral activity in human cells infected with HHV6. Level of infection was monitored by viral DNA quantification at different time points up to 7 days post infection. Among the synthetized derivatives, 9e showed a significative inhibitory effect on viral replication that lasted over 7 days, probably attributable to the particular combination of hydrophilic and hydrophobic substituents to the rhodanine moiety. Our results support the use of these amphipathic fusion inhibitors for the treatment of HHV-6 infections., (Copyright © 2021 Elsevier Inc. All rights reserved.)