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Aldaric acids are becoming valuable platform chemicals in bioeconomy and circular economy approaches. Among them, mucic acid (meso-galactaric acid) is gaining industrial attention as a bio-based precursor of adipic acid found in polyamides, and of 2,5-furan dicarboxylic acid, a valuable substitute for terephthalic acid in polyesters. A combination of detailed experimental protocols and conditions with DFT computational calculations for the synthesis of mucic acid from galactose are herein described. The product is obtained by reaction with diluted aqueous nitric acid as the oxidizing agent and the reaction medium. Optimized reaction conditions require 5 M nitric acid, 95 °C, galactose/HNO3 molar ratio 1 : 9, 100 g/L galactose concentration in the reaction medium. Computational calculations suggest that the oxidation mechanism may involve a contextual oxygen protonation and nitrate nucleophilic attack, leading to the oxidized product. The proposed mechanism requires a stoichiometry of 6 moles of nitric acid per galactose mole, albeit both experimental and computational data evidence that proton excess may be necessary to start the reaction. The reported study gives useful insights for the production of galactaric acid.

Azepane–based compounds are saturated seven-membered carbocycles where one carbon atom is replaced with a nitrogen atom. The azepane structure is also found in fused-ring derivatives endowed of a wide range of pharmacological activities. The azepane motif is in the top 100 most frequently used ring systems for small molecule drugs. Several synthetic methods toward the preparation of new azepane-based compounds scaffolds have gained significant interest and represent a continuous challenge for synthetic organic chemists. The synthesis of the azepane ring is based on different synthetic approaches such as: ring-closing reactions; ring-expansion reactions of cyclic compounds; and multistep sequences. The azepane based compounds continue to play great synthetic relevance because of their different biological activities such as anti-cancer, antimicrobial, anti-Alzheimer's disease and anticonvulsant activity. New synthetic methods for the construction of azepane derivatives endowed of relevant biological activity and good pharmacological profiles is expected in near future.

The ene-type reaction between (dithio)carboxylic acids and alkenes has been studied computationally by DFT and topological (analysis of the electron localization function, ELF) methods. The reaction proceeds under kinetic control and the observed differences in regioselectivity are well-explained by the relative stability of the different transition structures. In agreement with experimental observations, electron-rich alkenes lead to Markownikoff adducts while electron-poor alkenes lead to Michael adducts. In all cases the reaction proceeds through an only transition structure (one kinetic step) although a different synchronicity was observed depending on the alkene electronics. The ELF analysis of the reactions corroborates the existence of a transient carbocation (hidden intermediate) in the reactions with electron-rich alkenes. On the other hand, electron-poor alkenes proceed through a more synchronous concerted mechanism. It can be predicted that with electron-rich alkenes bearing highly donating the transient carbocations might be captured by a nucleophile.

An isoxazolidine is a pentatomic heterocycle, containing adjacent nitrogen and oxygen atoms. This ring is present in many compounds, showing significant biological activity, and plays a very significant role in the preparation of nucleotide and nucleoside analogs, which are used as anticancer and antiviral agents in medicinal chemistry. This chapter summarizes the last five years of the literature on the synthesis of isoxazolidines using conventional and modern methods, with reference to the structures of the products (i.e. substituted isoxazolidines, fused isoxazolidines, spiro-isoxazolidines, nucleoside and nucleotide analogs) obtained by cycloaddition reactions. Organocatalysts have been much used in the synthesis of substituted isoxazolidines in recent years. In particular, the employment of chiral metal complexes plays an important role in improving the reactivity and providing better control of the selectivity of cycloaddition reactions. The fused isoxazolidine presents a second ring fused to the isoxazolidine moiety, making the structure rigid and conformationally restricted.

The first example of supramolecular recognition of phosphocholine by a cavitand receptor has been reported here. The chemical structure of the receptor has been optimized by DFT calculations. The recognition mechanism is based on a "multi-topic approach", which leads to highly efficient (K value up to 107 M-1), selective and sensitive (ppb level) sensing of phosphocholine. The recognition mechanism proposed here is similar to those exploited by Nature, and paves the way for the realization of new sensors with important applications in medicine and security fields.

Functionalized polyhedral oligosilsesquioxanes (POSS) containing an isoxazolidine nucleus have been synthesized by microwave assisted 1,3-dipolar cycloaddition of N-methyl-C-alkoxycarbonyl nitrone 1 with POSS containing olefin moieties. The results of cycloaddition processes were rationalized by computational studies at the DFT level. The covalent conjugation of chitosan with the cycloadduct 3a leads to composite material CS-POSS 7 which was gelified using genipin as cross linking agent. The suitability of the system for bone tissue engineering purposes was evaluated by in vitro drug release studies using ketoprofen as a model drug and cytotoxicity assays performed on human fetal osteoblastic cells. The preliminary biological tests showed the lack of cytotoxicity of the hybrid material and suggest its potential role in bone tissue engineering applications.