Synthesis and characterisation of an enantiomerically pure scandium pentadienyl complex and its application in the polymerisation of rac-lactide

An enantiomerically pure constrained geometry scandium complex featuring a pentadienyl moiety was synthesised. The complex efficiently catalyses the polymerisation of rac-lactide to give slightly heterotactic, amorphous poly-(lactide).

Homochiral porous coordination polymer of EuIII for metal ion sensing and enantioselective adsorption

A novel three-dimensional homochiral porous coordination polymer was obtained by combining luminescent component Eu(III) with enantiomerically pure semirigid triangular organic ligand derived from (L)-α-leucine. Remarkably, it not only exhibited photoluminescence...

Enantioselectivity of Chiral Derivatives of Xanthones in Virulence Effects of Resistant Bacteria

Antimicrobial peptides are one of the lines of defense produced by several hosts in response to bacterial infections. Inspired by them and recent discoveries of xanthones as bacterial efflux pump inhibitors, chiral amides with a xanthone scaffold were planned to be potential antimicrobial adjuvants. The chiral derivatives of xanthones were obtained by peptide coupling reactions between suitable xanthones with enantiomerically pure building blocks, yielding derivatives with high enantiomeric purity. Among 18 compounds investigated for their antimicrobial activity against reference strains of bacteria and fungi, antibacterial activity for the tested strains was not found. Selected compounds were also evaluated for their potential to inhibit bacterial efflux pumps. Compound (R,R)-8 inhibited efflux pumps in the Gram-positive model tested and three compounds, (S,S)-8, (R)-17 and (R,S)-18, displayed the same activity in the Gram-negative strain used. Studies were performed on the inhibition of biofilm formation and quorum-sensing, to which the enantiomeric pair 8 displayed activity for the latter. To gain a better understanding of how the active compounds bind to the efflux pumps, docking studies were performed. Hit compounds were proposed for each activity, and it was shown that enantioselectivity was noticeable and must be considered, as enantiomers displayed differences in activity.

Synthesis of enantiomerically pure oxa[9]helicene derivatives via a nucleophilic cyclodehydration reaction of helical 1,1'-bibenzo[c]phenanthrenylidene-2,2'-dione

Enantiomerically pure 9-Substituted-11-oxa[9]helicene derivatives have been synthesized through furan-ring formation via a nucleophilic cyclodehydration reaction of enantiomerically pure helical polycondensed-2,2'-diphenoquinone derivatives (1,1'-bibenzo[c]phenanthrenylidene-2,2'-dione). (P)-2,2'-diphenoquinone derivatives afforded (P)-oxa[9]helicenes, while (M)-2,2'-diphenoquinone derivatives afforded their corresponding (M)-oxa[9]helicenes. Thus, the ring-closing reaction afforded the corresponding enantiomerically pure products without decreasing the enantiomeric excess and proceeded stereospecifically while retention the configuration. The thermal stability of oxa[9]helicene was studied by determining the decrease in the enantiomeric excess at various temperatures, and its racemization barrier was found to be 165.6 kJmol-1.

Unprecedented Monoterpenoid Polyprenylated Acylphloroglucinols with a Rare 6/6/5/4 Tetracyclic Core, Enhanced MCF-7 Cells’ Sensitivity to Camptothecin by Inhibiting the DNA Damage Response

(±)-Hypersines A–C (1–3), the three pairs of enantiomerically pure monoterpenoid polyprenylated acylphloroglucinols with an unprecedented 6/6/5/4 fused ring system, were isolated from Hypericum elodeoides. Their structures, including absolute configurations, were elucidated by comprehensive spectroscopic data, single-crystal X-ray diffraction, and quantum chemical calculations. The plausible, biosynthetic pathway of 1–3 was proposed. Moreover, the bioactivity evaluation indicated that 1a might be a novel DNA damage response inhibitor, and could enhance MCF-7 cell sensitivity to the anticancer agent, camptothecin.

Chemical and Enantioselective Analysis of the Essential Oils from Different Morphological Structures of Ocotea quixos (Lam.) Kosterm

The traditional Ecuadorian spice Ishpingo, characterized by a strong cinnamon-like aroma, is constituted by the dry cupules of Amazonian species Ocotea quixos. Nevertheless, bark and leaves also present aromatic properties and are sometimes used as substitutes. In the present study, the essential oils, distilled from these morphological structures, are comparatively analyzed for their chemical and enantiomeric compositions. A total of 88 components were identified with 2 orthogonal GC columns, whereas 79, corresponding to more than 94%, were also quantified with at least 1 column. Major compounds were (E)-methyl cinnamate in cupules (35.9–34.2%), (E)-cinnamaldehyde in bark (44.7–47.0%), and (E)-cinnamyl acetate (46.0–50.4%) in leaves. For what concerns the enantioselective analysis, 10 chiral terpenes and terpenoids were detected, of which 6 were present as enantiomeric pairs in at least 1 essential oil, the others being enantiomerically pure. Both quantitative and enantioselective analyses were submitted to Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA), where their results confirmed significative difference among the three products.

Tackling Stereochemistry in Drug Molecules with Vibrational Optical Activity

Chirality plays a crucial role in drug discovery and development. As a result, a significant number of commercially available drugs are structurally dissymmetric and enantiomerically pure. The determination of the exact 3D structure of drug candidates is, consequently, of paramount importance for the pharmaceutical industry in different stages of the discovery pipeline. Traditionally the assignment of the absolute configuration of druggable molecules has been carried out by means of X-ray crystallography. Nevertheless, not all molecules are suitable for single-crystal growing. Additionally, valuable information about the conformational dynamics of drug candidates is lost in the solid state. As an alternative, vibrational optical activity (VOA) methods have emerged as powerful tools to assess the stereochemistry of drug molecules directly in solution. These methods include vibrational circular dichroism (VCD) and Raman optical activity (ROA). Despite their potential, VCD and ROA are still unheard of to many organic and medicinal chemists. Therefore, the present review aims at highlighting the recent use of VOA methods for the assignment of the absolute configuration of chiral small-molecule drugs, as well as for the structural analysis of biologics of pharmaceutical interest. A brief introduction on VCD and ROA theory and the best experimental practices for using these methods will be provided along with selected representative examples over the last five years. As VCD and ROA are commonly used in combination with quantum calculations, some guidelines will also be presented for the reliable simulation of chiroptical spectra. Special attention will be paid to the complementarity of VCD and ROA to unambiguously assess the stereochemical properties of pharmaceuticals.

Synthesis of longhorn beetle pheromone components by proline mediated α-hydroxylation of alkylketones

The stereoselective synthesis of several components of the aggregation pheromones of numerous longhorn beetle species is described. These attractants consist in 3-hydroxy-2-alkylketones and 2,3-alkyldiols with chain lengths varying from six to ten carbons. The 3R- and 3S-series are generated by organocatalytic α-hydroxylation of alkylketones with nitrosobenzene in the presence of L- or D-proline, respectively, to obtain the hydroxyketones in high enantiomeric excess. Further reduction and chromatographic separation leads to the enantiomerically pure diols that complete the library