Search Results (7)

A comprehensive phytochemical investigation of the twigs/leaves and flower buds of Kolkwitzia amabilis, a rare deciduous shrub native to China, led to the isolation of 39 structurally diverse compounds. These compounds include 11 iridoid glycosides (1–4 and 7–13), 20 triterpenoids (5, 6, and 14–31), and 8 phenylpropanoids (32–39). Among these, amabiliosides A (1) and B (2) represent previously undescribed bis-iridoid glycosides, while amabiliosides C (3) and D (4) feature a unique bis-iridoid-monoterpenoid indole alkaloid scaffold with a tetrahydro-β-carboline-5-carboxylic acid moiety. Amabiliacids A (5) and B (6) are 24-nor-ursane-type triterpenoids characterized by an uncommon ∆^11,13(18) transannular double bond. Their chemical structures and absolute configurations were elucidated through spectroscopic data and electronic circular dichroism analyses. Compound 2 exhibited a moderate inhibitory effect against acetyl CoA carboxylase 1 (ACC1), with an IC₅₀ value of 9.6 μM. Lonicejaposide C (8), 3β-O-trans-caffeoyl-olean-12-en-28-oic acid (29), and (23E)-coumaroylhederagenin (31) showed notable inhibitory effects on ATP-citrate lyase (ACL), with IC₅₀ values of 3.6, 1.6, and 4.7 μM, respectively. Additionally, 3β-acetyl-ursolic acid (17) demonstrated dual inhibitory activity against both ACC1 and ACL, with IC₅₀ values of 10.3 and 2.0 μM, respectively. The interactions of the active compounds with ACC1 and ACL enzymes were examined through molecular docking studies. From a chemotaxonomic perspective, the isolation of bis-iridoid glycosides in this study may aid in clarifying the taxonomic relationship between the genera Kolkwitzia and Lonicera within the Caprifoliaceae family. These findings highlight the importance of conserving plant species with unique and diverse secondary metabolites, which could serve as potential sources of new therapeutic agents for treating ACC1/ACL-associated diseases. Full article

As part of a project on fused medium-sized ring systems as potential drugs, we have previously demonstrated the usefulness of Density Functional Theory (DFT) to evaluate amine nitrogen-based transannular interactions across the central 10-membered ring in the bioactive dibenzazecine alkaloid, protopine. A range of related hypothetical systems have been investigated, together with transannular interactions involving ring-embedded imino or azo group nitrogens and atoms or groups (Y) across the ring. Electrostatic potential energies mapped onto electron density surfaces in the different ring conformations were evaluated in order to characterise these conformations. Unexpectedly, the presence of sp² hybridised nitrogen atoms in the medium-sized rings did not influence the conformations appreciably. The strength and type of the N^…Y interactions are determined primarily by the nature of Y. This is also the case when the substituent on the interacting nitrogen is varied from CH₃ (protopine) to H or OH. With Y = BOH, very strong interactions were observed in protopine analogues, as well as in rings incorporating imino or azo groups. Strong to moderate interactions were observed with Y = CS, CO and SO in all ring systems. Weaker interactions were observed with Y = S, O and weaker ones again with an sp³ hybridised carbon (Y = CH₂). The transannular interactions can influence conformational preferencing and shape and change electron distributions at key sites, which theoretically could modify properties of the molecules while providing new or enhanced sites for biological target interactions, such as the H or OH substituent. The prediction of new strong transannular interaction types such as with Y = BOH and CS should be helpful in informing priorities for synthesis and other experimental studies. Full article

This paper describes the influence of the transannular π–π interaction in controlling the carrier transport in molecular wires by employing the STM break junction technique. Five pentaphenylene-based molecular wires that contained [2.2]paracyclophane-1,9-dienes (PCD) as the building block were prepared as model compounds. Functional substituents with different electronic properties, ranging from strong acceptors to strong donors, were attached to the top parallel aromatic ring and used as a gate. It was found that the carrier transport features of these molecular wires, such as single-molecule conductance and a charge-tunneling barrier, can be systematically controlled through the transannular π–π interaction. Full article

The physicochemical properties and reactivity of macrocycles are critically shaped by their conformations. In this work, we have identified seven conformations of the macrocyclic ketone cyclododecanone using chirped-pulse Fourier transform microwave spectroscopy in combination with ab initio and density functional theory calculations. Cyclododecanone is strongly biased towards adopting a square configuration of the heavy atom framework featuring three C–C bonds per side. The substitution and effective structures of this conformation have been determined through the observation of its ¹³C isotopologues. The minimisation of transannular interactions and, to a lesser extent, HCCH eclipsed configurations drive conformational preferences. Our results contribute to a better understanding of the intrinsic forces mediating structural choices in macrocycles. Full article

Medium-sized heterocycles (with 8 to 11 atoms) constitute important structural components of several biologically active natural compounds and represent promising scaffolds in medicinal chemistry. However, they are under-represented in the screening of chemical libraries as a consequence of being difficult to access. In particular, methods involving intramolecular bond formation are challenging due to unfavorable enthalpic and entropic factors, such as transannular interactions and conformational constraints. The present review focuses on the synthesis of medium-sized heterocycles by transition-metal-catalyzed intramolecular cyclization, which despite its drawbacks remains a straightforward and attractive synthesis strategy. The obtained heterocycles differ in their nature, number of heteroatoms, and ring size. The methods are classified according to the metal used (palladium, copper, gold, silver), then subdivided according to the type of bond formed, namely carbon–carbon or carbon–heteroatom. Full article

The mechanism of reactions of silatranes and germatranes, and their bicyclic and monocyclic analogues with one molecule of methanol or ethanol, was studied at the Density Functional Theory (DFT) B3PW91/6-311++G(df,p) level of theory. Reactions of 1-substituted sil(germ)atranes, 2,2-disubstituted sil(germ)ocanes, and 1,1,1-trisubstituted hyposil(germ)atranes with alcohol (methanol, ethanol) proceed in one step through four-center transition states followed by the opening of a silicon or germanium skeleton and the formation of products. According to quantum chemical calculations, the activation energies and Gibbs energies of activation of reactions with methanol and ethanol are close, their values decrease in the series of atranes–ocanes–hypoatranes for interactions with both methanol and ethanol. The reactions of germanium-containing derivatives are characterized by lower activation energies in comparison with the reactions of corresponding silicon-containing compounds. The annular configurations of the product molecules with electronegative substituents are stabilized by the transannular N→X (X = Si, Ge) bond and different intramolecular hydrogen contacts with the participation of heteroatoms of substituents at the silicon or germanium. Full article

The chiroptical properties of enantiomerically pure bicyclo[3.3.1]nona-2,6-diene-2,6-dicarbonitrile and related acids were studied by circular dichroism spectroscopy and theoretical computations. A consideration of the molecular structure of the synthesized difunctional compounds revealed that chromophores are predisposed to transannular through-space interaction due to a favourable conformation of the bicyclic skeleton and a rather small interchromophoric distance. Evidence for non-exciton-type coupling between the two acrylonitrile and acrylate moieties in 3 and 4, respectively, was obtained by chiroptical spectroscopy and DFT calculations. Full article