Replacing fossil fuels with renewable, bio‐based alternatives is inevitable for the modern chemical industry, in line with the 12 principles of green chemistry. 2,5‐Furandicarboxylic acid (FDCA) is a promising platform molecule that can be derived from 5‐hydroxymethyl furfural (HMF) via sustainable electrochemical oxidation. Herein, we demonstrate TEMPO‐mediated electrooxidation of HMF to FDCA in ElectraSyn 2.0 using inexpensive commercially available electrodes: graphite anode and stainless‐steel cathode, thereby avoiding the often cumbersome electrode preparation. Key parameters such as concentration of HMF, KOH, and catalyst loading were optimized by experimental design. Under the optimized conditions, using only a low amount of TEMPO (5 mol %), high yield and Faradaic efficiency of 96 % were achieved within 2.5 h. Moreover, since FDCA is a monomer of the bio‐based poly(ethylene furanoate), PEF, we aimed to investigate its recovery by depolymerization, which could be of paramount importance in the circular economy of the FDCA. For this, a new polar aprotic solvent, methyl sesamol (MeSesamol), was used, allowing the facile depolymerization of PEF at room temperature with high monomer yields (up to 85 %), while the cosolvent MeSesamol was recycled with high efficiency (95–100 %) over five reaction cycles.

This work presents the first successful applications of cinchona-thiosquaramides in asymmetric reactions. Binaphthyl-cinchona squaramides and thiosquaramides were synthesised, and then used as organocatalysts to promote the catalytic enantioselective Michael addition reaction of pentane-2,4-dione to trans-β-nitrostyrene with excellent yields (up to 99%) and enantioselectivities (up to 99% ee) at as low as 0.2 mol% catalyst loadings. Thiosquaramides gave higher enantioselectivities (up to 92% ee) in conjugate addition reaction of lawsone to β,γ-unsaturated α-keto ester than its oxo analogue, with high yields (up to 100%). Also, only thiosquaramide could catalyse the aza-Diels–Alder addition reaction of 2-siloxydiene to benzylideneacetone. Furthermore, quantum chemical computations showed that the geometrical structure of binaphthyl-cinchona thiosquaramide is similar to that of squaramide.

Since the first application of natural quinine as an anti-malarial drug, cinchona alkaloids and their derivatives have been exhaustively studied for their biological activity. In our work, we tested 13 cinchona alkaloid organocatalysts, synthesised from quinine. These derivatives were screened against MES-SA and Dx5 uterine sarcoma cell lines for in vitro anticancer activity and to investigate their potential to overcome P-glycoprotein (P-gp) mediated multidrug resistance (MDR). Decorating quinine with hydrogen-bond donor units, such as thiourea and (thio)squaramide, resulted in decreased half-maximal growth inhibition values on both cell lines (1.3-21 µM) compared to quinine and other cinchona alcohols (47-111 µM). Further cytotoxicity studies conducted in the presence of the P-gp inhibitor tariquidar indicated that several analogues, especially cinchona amines and squaramides, but not thiosquaramide, were expelled from MDR cells by P-gp. Similarly to the established P-gp inhibitor quinine, 6 cinchona analogues were shown to inhibit calcein-AM efflux. Interestingly, quinine and didehydroquinine exhibited a marginally increased toxicity against the multidrug resistant Dx5 cells. Collateral sensitivity of the MDR cell line was more pronounced when the cinchona thiosquaramide was complexed with Cu(II) acetate. Based on the results, cinchona derivatives are good anticancer candidates for further drug development.

Numerous cinchona organocatalysts with different substituents at their quinuclidine unit have been described and tested, but the effect of those saturation has not been examined before. This work presents the synthesis of four widely used cinchona-based organocatalyst classes (hydroxy, amino, squaramide, and thiourea) with different saturation on the quinuclidine unit (ethyl, vinyl, ethynyl) started from quinine, the most easily available cinchona derivative. Big differences were found in basicity of the quinuclidine unit by measuring the pK_a values of twelve catalysts in six solvents. The effect of differences was examined by testing the catalysts in Michael addition reaction of pentane-2,4-dione to trans-β-nitrostyrene. The 1.6–1.7 pK_a deviation in basicity of the quinuclidine unit did not result in significant differences in yields and enantiomeric excesses. Quantum chemical calculations confirmed that the ethyl, ethynyl, and vinyl substituents affect the acid-base properties of the cinchona-thiourea catalysts only slightly, and the most active neutral thione forms are the most stable tautomers in all cases. Due to the fact that cinchonas with differently saturated quinuclidine substituents have similar catalytic activity in asymmetric Michael addition application of quinine-based catalysts is recommended. Its vinyl group allows further modifications, for instance, recycling the catalyst by immobilization.

Organocatalysis has become a powerful tool in synthetic chemistry, providing a cost-effective alternative to traditional catalytic methods. The immobilisation of organocatalysts offers the potential to increase catalyst reusability and efficiency in organic reactions. This article reviews the key parameters that influence the effectiveness of immobilised organocatalysts, including the type of support, immobilisation techniques and the resulting interactions. In addition, the influence of these factors on catalytic activity, selectivity and recyclability is discussed, providing an insight into optimising the performance of immobilised organocatalysts for practical applications in organic chemistry.