Dehydration of alcohols catalyzed by copper(II) sulfate: type II dyotropic reactions and stepwise mechanisms.

Dehydration of alcohols in the presence of copper(II) sulfate has been analyzed computationally. Density functional theory (DFT) calculations on selected alcohols indicate that this reaction can take place two possible mechanisms: (a) concerted - although asynchronous - type II dyotropic reactions, or (b) stepwise E1-like processes, in which cleavage of the C-O bond occurs in the first step, followed by proton elimination. Our calculations show the relationship between the initial alcohol structure and the preferred mechanism, which is a type II dyotropic reaction for primary alcohols, whereas a stepwise process is the favored one when stable carbocation intermediates are energetically accessible.

Indomuscone-Based Sterically Encumbered Phosphines as Ligands for Palladium-Catalyzed Reactions.

The fragrance compound indomuscone is used here as a scaffold to prepare two different sterically hindered phosphines, one aromatic and another alkylic, in good yields, after four synthetic steps. The new phosphines show enhanced electronic and steric properties when compared to benchmark commercial phosphine ligands, which is reflected in the catalytic results obtained for representative palladium-catalyzed reactions such as the telomerization reaction, the Buchwald-Hartwig and Suzuki cross-coupling reactions of chloroaromatic rings, and the semi-hydrogenation reaction of an alkyne. In particular, the indomuscone-based aromatic phosphine ligand leads to the highest selectivity for the tail-to-head telomerization product between isoprene and methanol, while the indomuscone-based alkylic phosphine ligand shows extraordinary similarities with the Buchwald-type SPhos phosphine ligand.

Spectroscopic dataset of Hedione's derivatives gathered during process development.

The dataset of spectroscopic analysis performed on starting materials, intermediates, and products relating to the synthesis of Hedione are hereby presented. The data were acquired in Durham university during the period between October 2020 and September 2021 for the development of a preparative method to Dehydrohedione. The latter is a key intermediate for the synthesis of Hedione, an important fragrance ingredient.

Parts-per-million of ruthenium catalyze the selective chain-walking reaction of terminal alkenes.

The chain-walking of terminal alkenes (also called migration or isomerization reaction) is currently carried out in industry with unselective and relatively costly processes, to give mixtures of alkenes with significant amounts of oligomerized, branched and reduced by-products. Here, it is shown that part-per-million amounts of a variety of commercially available and in-house made ruthenium compounds, supported or not, transform into an extremely active catalyst for the regioselective migration of terminal alkenes to internal positions, with yields and selectivity up to >99% and without any solvent, ligand, additive or protecting atmosphere required, but only heating at temperatures >150 °C. The resulting internal alkene can be prepared in kilogram quantities, ready to be used in nine different organic reactions without any further treatment.

Design and Synthesis of Fsp(3)-Rich, Bis-Spirocyclic-Based Compound Libraries for Biological Screening.

The exploration of innovative chemical space is a critical step in the early phases of drug discovery. Bis-spirocyclic frameworks occur in natural products and other biologically relevant metabolites and show attractive features, such as molecular compactness, structural complexity, and three-dimensional character. A concise approach to the synthesis of bis-spirocyclic-based compound libraries starting from readily available commercial reagents and robust chemical transformations has been developed.

Design and synthesis of 1,1-disubstituted-1-silacycloalkane-based compound libraries.

The introduction of silicon in biologically-relevant molecules represents an interesting medicinal chemistry tactic. Its use is mainly confined to the fine-tuning of specific molecular properties and organosilicon compounds are underrepresented in typical screening libraries. As part of the European Lead Factory efforts to generate novel, drug discovery-relevant chemical matter, the design and synthesis of 1,1-disubstituted-1-silacycloalkane-based compound libraries is described.

Non-peptidic cell-penetrating agents: synthesis of oligomeric chiral bicyclic guanidinium vectors.

Polycationic oligo(chiral bicyclic guanidines) constitute useful non-peptidic penetrating agents for cell uptake and protein surface recognition. We report herein improved and selective procedures for the preparation of oligoguanidinium scaffolds linked through thioether bonds, with similar or different groups and functions at both ends of the chain. Two synthetic strategies were developed to obtain these compounds in relatively good yields from a common thioacetate precursor: generation of a disulfide intermediate or thiolate formation.

Systemic antibacterial activity of novel synthetic cyclic peptides.

Cyclic peptides with an even number of alternating d,l-alpha-amino acid residues are known to self-assemble into organic nanotubes. Such peptides previously have been shown to be stable upon protease treatment, membrane active, and bactericidal and to exert antimicrobial activity against Staphylococcus aureus and other gram-positive bacteria. The present report describes the in vitro and in vivo pharmacology of selected members of this cyclic peptide family.

Recognizing a single base in an individual DNA strand: a step toward DNA sequencing in nanopores.

Functional supramolecular chemistry at the single-molecule level. Single strands of DNA can be captured inside α-hemolysin transmembrane pore protein to form single-species α-HL·DNA pseudorotaxanes. This process can be used to identify a single adenine nucleotide at a specific location on a strand of DNA by the characteristic reductions in the α-HL ion conductance.

Single DNA rotaxanes of a transmembrane pore protein.

Supramolecular chemistry at the single-molecule level. An α-hemolysin transmembrane pore can be threaded in a desired orientation by DNA-PEG hybrid strands to yield functional rotaxanes. The single-molecule rotaxanes display stable and reversible two-state switching capacity depending on the applied potential, orientation, and the method of threading and capture used.

Modulating ion channel properties of transmembrane peptide nanotubes through heteromeric supramolecular assemblies.

A selective heteromeric supramolecular assembly process is devised to create functional single channels of altered ion conductance, charge selectivity, and rectification. The hollow transmembrane tubular structure produced spontaneously from the self-assembly of cyclic-d,l-alpha-peptides in lipid bilayers is modified by designer cyclic peptide "cap" subunits that bind site-selectively at the mouth of the channel assembly.

A Synthetic Pore-Mediated Transmembrane Transport of Glutamic Acid.

Transported to the other side: Cyclic D,L-α-peptides self-assemble in lipid bilayers into transmembrane ion channels that may allow efficient transport of glutamic acid. The molecular transport is size/shape selective, as evidenced by the high transport rates observed with cyclodecapeptide-based transmembrane pores but not with the smaller cyclooctapeptide analogue.