Copper-Catalyzed Dearomative 1,2-Hydroamination.

Catalytic olefin hydroamination reactions are some of the most atom-economical transformations that bridge readily available starting materials-olefins and high-value-added amines. Despite significant advances in this field over the last two decades, the formal hydroamination of nonactivated aromatic compounds remains an unsolved challenge. Herein, we report the extension of olefin hydroamination to aromatic π-systems by using arenophile-mediated dearomatization and Cu-catalysis to perform 1,2-hydroamination on nonactivated arenes. This strategy was applied to a variety of substituted arenes and heteroarenes to provide general access to structurally complex amines. We conducted DFT calculations to inform mechanistic understanding and rationalize unexpected selectivity trends. Furthermore, we developed a practical, scalable desymmetrization to deliver enantioenriched dearomatized products and enable downstream synthetic applications. We ultimately used this dearomative strategy to efficiently synthesize a collection of densely functionalized small molecules.

Unveiling the structural mechanism of a G-quadruplex pH-Driven switch.

The human telomere oligonucleotide, d[TAGGG(TTAGGG)2TTAGG] (TAGGG), can adopt two distinct 2-G-quartet G-quadruplex structures at pH 7.0 and 5.0, referred to as the TD and KDH+ forms, respectively. By using a combination of NMR and computational techniques, we determined high-resolution structures of both forms, which revealed unique loop architectures, base triples, and base pairs that play a crucial role in the pH-driven structural transformation of TAGGG. Our study demonstrated that TAGGG represents a reversible pH-driven switch system where the stability and pH-induced structural transformation of the G-quadruplexes are influenced by the terminal residues and base triples. Gaining insight into the factors that regulate the formation of G-quadruplexes and their pH-sensitive structural equilibrium holds great potential for the rational design of novel DNA based pH-driven switches. These advancements in understanding create exciting opportunities for applications in the field of nanotechnology, specifically in the development of bio-nano-motors.

Synthesis of (+)-ribostamycin by catalytic, enantioselective hydroamination of benzene.

Aminoglycosides (AGs) represent a large group of pseudoglycoside natural products, in which several different sugar moieties are harnessed to an aminocyclitol core. AGs constitute a major class of antibiotics that target the prokaryotic ribosome of many problematic pathogens. Hundreds of AGs have been isolated to date, with 1,3-diaminocyclohexanetriol, known as 2-deoxystreptamine (2-DOS), being the most abundant aglycon core. However, owning to their diverse and complex architecture, all AG-based drugs are either natural substances or analogues prepared by late-stage modifications. Synthetic approaches to AGs are rare and lengthy; most studies involve semi-synthetic reunion of modified fragments. Here we report a bottom-up chemical synthesis of the 2-DOS-based AG antibiotic ribostamycin, which proceeds in ten linear operations from benzene. A key enabling transformation involves a Cu-catalyzed, enantioselective, dearomative hydroamination, which set the stage for the rapid and selective introduction of the remaining 2-DOS heteroatom functionality. This work demonstrates how the combination of a tailored, dearomative logic and strategic use of subsequent olefin functionalizations can provide practical and concise access to the AG class of compounds.

Reversible pH Switch of Two-Quartet G-Quadruplexes Formed by Human Telomere.

A four-repeat human telomere DNA sequence without the 3'-end guanine, d[TAGGG(TTAGGG)2 TTAGG] (htel1-ΔG23) has been found to adopt two distinct two G-quartet antiparallel basket-type G-quadruplexes, TD and KDH(+) in presence of KCl. NMR, CD, and UV spectroscopy have demonstrated that topology of KDH(+) form is distinctive with unique protonated T18⋅A20(+) ⋅G5 base triple and other capping structural elements that provide novel insight into structural polymorphism and heterogeneity of G-quadruplexes in general. Specific stacking interactions amongst two G-quartets flanking base triples and base pairs in TD and KDH(+) forms are reflected in 10 K higher thermal stability of KDH(+) . Populations of TD and KDH(+) forms are controlled by pH. The (de)protonation of A20 is the key for pH driven structural transformation of htel1-ΔG23. Reversibility offers possibilities for its utilization as a conformational switch within different compartments of living cell enabling specific ligand and protein interactions.

Photodegradation of methoxy substituted curcuminoids.

Photodegradation of dimethoxy curcuminoids in acetonitrile solution was found to depend on the position of the methoxy group bonded to the phenyl ring. The rate of decomposition was expressed as the lifetime of the decomposing substrate, being the shortest in the case of the 3,5-dimethoxy and the longest for the 2,5-dimethoxy derivative. For the 3,5-dimethoxy curcuminoid, the major degradation products were 3,5-dimethoxy benzaldehyde, 3,5-dimethoxybenzoic acid and the Z and E isomers of dimethoxy cinnamic acid, together forming about 90% of the reaction mixture. Minor products found were 4,5-bis(3,5-dimethoxyphenyl)hex-2-endionic acid, and products with the molecular formula C23H24O6 and C23H22O6 attributed to the reaction of intramolecular [2+2] cycloaddition of the dimethoxy curcuminoid and the dioxygenated bicyclopentadione derivative (C23H24O8) derived from autoxidative transformation of the dimethoxy curcuminoid.

Crystal structures and emission properties of the BF2 complex 1-phenyl-3-(3,5-dimethoxyphenyl)-propane-1,3-dione: multiple chromisms, aggregation- or crystallization-induced emission, and the self-assembly effect.

It is known that electron donating groups have quite a different effect on the π-delocalization of a conjugate system when bonded at ortho and para as compared to meta positions in the phenyl ring. In the present work, the BF2 complex of 1-phenyl-3-(3,5-dimethoxyphenyl)-propane-1,3-dione (1), a molecule with two methoxy groups in one of the phenyl rings at meta positions, was prepared. Compound 1 exists as two polymorphs having different mutual orientations of the two methoxy groups: in polymorph A away from each other (termed anti), while in polymorph B one methoxy group is oriented toward the other (syn-anti). In both crystals, the molecules which are antiparallel (the subPh rings as well as dioxaborine are on opposite sides) form stacks through face-to-face π-π interactions, while in polymorph A the crystal packing is further stabilized by intermolecular C(phenyl)-H···F and C(methoxy)-H···F hydrogen bonds. Solid A possesses numerous chromic effects, including mechano-, thermo-, and chronochromism, though the latter to a lesser extent, as well as the effect of rearrangement of the amorphous phase into a more stable crystalline phase A, associated with crystallization-induced emission enhancement (CIEE). The solid-state emission can be repeatedly switched regarding its color and efficiency with excellent reversibility by external stimuli. On the other hand, crystalline solid B undergoes thermal interconversion of syn-anti to the anti conformer. Compound 1 shows a solvatochromic effect (SE), is aggregation-induced emission (AIE) active, and through the sublimation process displays self-assembling crystalline platelike microstructures or microfibers that reveal an obvious optical waveguide effect.

Structures in solid state and solution of dimethoxy curcuminoids: regioselective bromination and chlorination.

BACKGROUND: Several papers described the structure of curcumin and some other derivatives in solid and in solution. In the crystal structure of curcumin, the enol H atom is located symmetrically between both oxygen atoms of the enolone fragment with an O···O distance of 2.455 Å, which is characteristic for symmetrical H-bonds. In the solution, the geometry of the enolone fragment is attributed to the inherent disorder of the local environment, which solvates one of the basic sites better than the other, stabilizing one tautomer over the other. In this paper, how the position of methoxy groups in dimethoxy curcuminoids influence the conformation of molecules and how the halogen atoms change it when they are bonded at α-position in keto-enol part of molecules is described. RESULTS: Six isomers of dimethoxy curcuminoids were prepared. Conformations in solid state, which were determined by X-ray single crystallography and 1H MAS and 13C CPMAS NMR measurements, depend on the position of methoxy groups in curcuminoid molecules. In solution, a fast equilibrium between both keto-enol forms exists. A theoretical calculation finding shows that the position of methoxy groups changes the energy of HOMO and LUMO. An efficient protocol for the highly regioselective bromination and chlorination leading to α-halogenated product has been developed. All α-halogenated compounds are present mainly in cis keto-enol form. CONCLUSIONS: The structures in solid state of dimethoxy curcuminoids depend on the position of methoxy groups. The NMR data of crystalline solid samples of 3,4-diOCH3 derivative, XRD measurements and X-ray structures lead us to the conclusion that polymorphism exists in solids. The same conclusion can be done for 3,5-diOCH3 derivative. In solution, dimethoxy curcuminoids are present in the forms that can be described as the coexistence of two equivalent tautomers being in fast equilibrium. The position of methoxy groups has a small influence on the enolic hydrogen bond. Theoretical calculations show that the energy gap between HOMO and LUMO depend on the position of methoxy groups and are lower in solution. Chlorination and bromination on α-position of 1,3-diketone moiety do not change the preferential form being cis keto-enol as in parent compounds.