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The alkene-isocyanate cycloaddition method affords β-lactams from glycals with high regio- and stereoselectivity, but the factors that determine substrate reactivity are poorly understood. Thus, we synthesized a library of 17 electron-rich alkenes (glycals) with varied protecting groups to systematically elucidate the factors that influence their reactivity toward the electron-poor trichloroacetyl isocyanate. The experimentally determined reaction rates exponentially correlate with the computationally determined highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) gap and natural bond orbital (NBO) valence energies. The electron-withdrawing ability of the protecting groups, but not bulk, impacts the electron density of the glycal allyloxocarbenium system when oriented

Efforts to develop synthetic carbohydrate polymers, despite their potential uses in biomedical applications, lag behind those of synthetic polypeptides and polynucleotides due to their structural complexity and the challenging methods associated with their synthesis. While carbohydrate polymers with functional groups such as carboxylic acids (alginic acid) and amines (chitosan) are used as hydrogels and nanocarriers for therapeutics, the potential for contamination, batch-to-batch variation, and poor chemical definition limits their translation to clinical application. Inspired by these challenges, we describe efforts towards the design and synthesis of enantiopure, amine-functional carbohydrate polymers with defined stereochemistry, narrow molecular weight distributions, helical confirmations, water solubility, and degrees of polymerization up to 50. Multiple synthetic routes are described, along with their limitations, to highlight the role of protecting group choices in the successful development of these polymers.

The first bio-inspired N-Heterocyclic Carbene (NHC)-catalyzed Stetter reaction in aqueous medium is reported with benzaldehyde and chalcone as model substrates. A screening of azolium salts as precatalysts revealed the remarkable efficiency of synthetic thiazolium salt 8 (up to 90% conversion in pure water at 75 °C). The reaction was successfully extended to various simple aldehyde substrates. The effect of temperature was also investigated in order to extend the reaction to lower temperature allowing a potential application to sensitive biomolecules. This study highlighted the influence of both solvent and temperature on the 1,4-diketone 3/benzoin 4 ratio. New precatalysts 26 and 27 were designed and synthesized to explore a possible compartmentalization of the reaction in aqueous conditions. Owing to the use of inexpensive metal-free N-Heterocyclic Carbene (NHC) as a bioinspired catalyst, we anticipate that this green strategy in aqueous conditions will be attractive for bioconjugation of many biomolecule-type aldehydes and enone derivatives.

Hybrid synthetic amphiphilic biomolecules are emerging as promising supramolecular materials for biomedical and technological applications. Herein, recent progress in the field of nucleic acid based lipids is highlighted with an emphasis on their molecular design, synthesis, supramolecular properties, physicochemical behaviors, and applications in the field of health science and technology. In the first section, the design and the study of nucleolipids are in focus and then the glyconucleolipid family is discussed. In the last section, recent contributions of responsive materials involving nucleolipids and their use as smart drug delivery systems are discussed. The supramolecular materials generated by nucleic acid based lipids open new challenges for biomedical applications, including the fields of medicinal chemistry, biosensors, biomaterials for tissue engineering, drug delivery, and the decontamination of nanoparticles.

An N-Heterocyclic Carbene (NHC) catalyzed biomimetic Stetter reaction was applied for the first time as a bioconjugation reaction to sensitive nucleoside-type biomolecules to provide original pyrrole linked nucleolipids. A versatile approach allowed the functionalization of thymidine at the three reactive positions (O-5′, O-3′ and N-3) providing a structural diversity oriented synthesis. This strategy was applied to the synthesis of an original glyconucleolipid amphiphile in the hope that the pyrrole aromatic moiety would induce additional self-assembling properties.