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Asymmetric Michael addition of chiral 2-fluoroenaminoesters derived from (S)-1-phenylethylamine to [alpha]-substituted methyl acrylate which leads to diastereomeric [gamma]-substituted [gamma]-fluoroglutamate precursors is reported. The results from [auper 19]F and [super 1]H NMR experiments and ab initio computations demonstrated the Michael addition diastereoselectivity for the asymmetric conjugate addition of fluorinated chiral [beta]-enaminoester to methyl [alpha]-acetamidoacrylate.

A heterochiral 1,3,5-benzene tricarboxamide (BTA) monomer, derived from valine dodecyl ester, forms long rods in cyclohexane whilst its homochiral analogue assembles into dimers only at the same concentration. This highly original assembly behaviour is related to the destabilization of the dimeric structure containing the two heterochiral monomers as corroborated by a combined experimental and computational study. [ABSTRACT FROM AUTHOR]

Squalenoyl conjugates of semaxanib and sunitinib, two potent antiangiogenic (pyrrolyl)methylidenyl-substituted oxindole multitarget tyrosine kinase inhibitors, were synthesized with a hemiaminal-based pH-sensitive linker. The prodrugs were prepared according to a three-step sequence involving (i) N-alkylation with chloromethoxy-triisopropylsilane; (ii) desilylation; and (iii) acylation with trisnorsqualenic acid. These squalenoyl prodrugs were found to self-assemble into nanoassemblies in aqueous media without the need for any surfactant. The nanosized aggregates were characterized by dynamic light scattering and transmission electron microscopy, and appeared to be stable in water for several days, as determined by particle-size measurement. In vitro biological studies showed that squalenoyl sunitinib nanoassemblies are notably cytotoxic against the human umbilical vein endothelial cell line (HUVEC), which is involved in the tumor vessel formation. [ABSTRACT FROM AUTHOR]

Aggregation of supramolecular helices, for example through interdigitation of their alkyl side chains or through more directional supramolecular interactions, leads to hierarchical architectures with original structural and chiroptical properties. However, when a chiral monomer (the "sergeant") is introduced as a minor component in these assemblies composed of a majority of achiral monomers (the "soldiers"), it is not clear how the aggregation changes the ability of the sergeant to induce a preferential helicity to the polymer main chain (the so-called "sergeants-and-soldiers" effect). This study reports a detailed investigation of the influence of [Cu(OAc) 2 ⋅H 2 O] coordination on the structure and chiroptical properties of helical hydrogen-bonded co-assemblies composed of a catalytically-active benzene-1,3,5-tricarboxamide (BTA) monomer, acting as the "soldier", and an enantiopure BTA monomer derived from cyclohexylalanine, playing the role of the "sergeant". The copper actually significantly influences the extent of the "sergeants-and-soldiers" effect since it acts as a crosslink that induces some chiral defects in the supramolecular helices. These crosslinks appear to be preserved during the catalytic hydrosilylation of 4-nitroacetophenone. The aggregation of helices through the formation of copper crosslinks is reversible since homochiral single helices are exclusively formed in the case of sergeant-rich assemblies. The fact that both main chain and side chain aggregation affects the chiroptical properties of supramolecular helices must be considered in the design of elaborated chiral materials., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

While the generation of aryl radicals by photoredox catalysis under reductive conditions is well documented, it has remained challenging under an oxidative pathway. Because of the easy photo-oxidation of alkyl bis-catecholato silicates, a general study of phenyl silicates bearing substituted catecholate ligands has been achieved. The newly synthesized phenyl silicates have been fully characterized, and their reactivity has been explored. It was found that, thanks to the substitution of the catecholate moiety, notably with the 4-cyanocatecholato ligand, the phenyl radical could be generated and trapped. Computational studies provided a rationale for these findings., (© 2021 Wiley-VCH GmbH.)

Ferrociphenols, especially those possessing a heterocycle at the terminus of an aliphatic chain, display strong anticancer activity through a novel redox mechanism that generates active metabolites such as quinone methides (QMs). X-ray crystallography and UV/Vis spectroscopy reveal that the specific lone pair (lp)-π interaction between a carbonyl group of the imide and the quinone motif of the QM plays an important role in the exceptional cytotoxic behaviour of their imido-ferrociphenol precursors. This intramolecular lp-π interaction markedly enhanced the stability of the QMs and lowered the pK a values of the corresponding phenol/phenolate couples. As the first example of such a non-covalent interaction that stabilizes QMs remotely, it not only expands the scope of the lp-π interaction in supramolecular chemistry, but also represents a new mode of stabilization of a QM. This unprecedented application of lp-π interactions in imido-ferrociphenol anticancer drug candidates may also have great potential in drug discovery and organocatalyst design., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)