As a bulk component of plant biomass, cellulose plays a key role in the route leading to viable chemicals from renewable resources. Pyrolysis is a thermal treatment that converts cellulose into a liquid material (bio-oil) containing dehydrated monomers, among which the anhydrosugars levoglucosan (LGA) and levoglucosenone (LGO) have been widely investigated as chiral multifunctional synthons. A chiral cyclic hydroxylactone (LAC, 1) is also produced, but its potential as chemical intermediate has never been scrutinised, probably because it is generated only in minute amounts. In this study, experiments with a fixed bed reactor showed that the yields of LAC could be significantly increased by pyrolysing cellulose for few minutes at 350 °C in the presence of nanopowder (NP) titanium dioxide, aluminium oxide, and aluminium titanate (AlTi). When pyrolysis was conducted with NP AlTi at 500 °C, LAC became the principal anhydromonosaccharide and could be isolated from the resulting bio-oil with simple operations (6% overall yield). Its structure could be definitively assigned to the (1R,5S)-1-hydroxy-3,6-dioxabicyclo[3.2.1]octan-2-one by extensive NMR analysis and high resolution EI-MS experiments, providing a firm evidence of its previous attribution. The significance of LAC as building block for follow-up bioproducts was evaluated in some examples, including the synthesis of a suitable amide by the effective and eco-friendly microwave assisted methodology.

YTHDF proteins bind the N ⁶-methyladenosine (m6A)-modified mRNAs, influencing their processing, stability, and translation. Therefore, the members of this protein family play crucial roles in gene regulation and several physiological and pathophysiological conditions. YTHDF proteins contain a hydrophobic pocket that accommodates the m6A embedded in the RRACH consensus sequence on mRNAs. We exploited the presence of this cage to set up an m6A-competitive assay and performed a high-throughput screen aimed at identifying ligands binding in the m6A pocket. We report the organoselenium compound ebselen as the first-in-class inhibitor of the YTHDF m6A-binding domain. Ebselen, whose interaction with YTHDF proteins was validated via orthogonal assays, cannot discriminate between the binding domains of the three YTHDF paralogs but can disrupt the interaction of the YTHDF m6A domain with the m6A-decorated mRNA targets. X-ray, mass spectrometry, and NMR studies indicate that in YTHDF1 ebselen binds close to the m6A cage, covalently to the Cys412 cysteine, or interacts reversibly depending on the reducing environment. We also showed that ebselen engages YTHDF proteins within cells, interfering with their mRNA binding. Finally, we produced a series of ebselen structural analogs that can interact with the YTHDF m6A domain, proving that ebselen expansion is amenable for developing new inhibitors. Our work demonstrates the feasibility of drugging the YTH domain in YTHDF proteins and opens new avenues for the development of disruptors of m6A recognition.

Flavonoids are metabolites widely distributed in plants and commonly present in foods, such as fruits and vegetables. Pectolinarin, which belongs to the flavone subclass, has attracted considerable attention due to its presence in many medicinal plants. It has turned out to be a good biological agent especially due to its antioxidant, anti-inflammatory, antidiabetic, and antitumor activities, evaluated both in vitro and in vivo. Its aglycone, the metabolite pectolinarigenin, is also known for a series of biological properties including anti-inflammatory and antidiabetic effects. In the first overview on the two metabolites here presented, their collection, isolation and the results of their biological evaluation are reported.