Synthesis and Fungicidal Activity of Hydrated Geranylated Phenols against Botrytis cinerea

Botrytis cinerea is a ubiquitous fungus that affects hundreds of plants, resulting in economic losses to the horticulture and fruit industry. The search for new antifungal agents is a matter of current interest. Thus, in this work a series of geranylated phenols in which the side alkyl chain has been hydrated have been synthesized, and their activity against B. cinerea has been evaluated. The coupling of phenol and geraniol has been accomplished under microwave irradiation obtaining the highest reaction yields in the shortest reaction times. Hydration of the side chain was carried out in dioxane with p-toluenesulfonic acid polymer-bound as the catalyst. All synthesized compounds were tested against B. cinerea using the growth inhibition assay and EC50 values were determined. The results show that activity depends on the number and nature of functional groups in the phenol ring and hydration degree of the geranyl chain. The most active compound is 1,4-dihydroquinone with one hydroxyl group attached at the end of the alkyl chain. Results from a molecular docking study suggest that hydroxyl groups in the phenol ring and alkyl chain are important in the binding of compounds to the active site, and that the experimental antifungal activity correlates with the number of H-bond that can be formed in the binding site.

Synthesis of a new phorbazole and its derivatives

Phorbazoles are chlorinated marine alkaloids isolated from sea sponges and nudibranchs. In this work, a convenience synthetic method leading to a new phorbazole and its derivatives was developed. This synthesis of the novel phorbazole G and its derivatives has been Phorbazoles are chlorinated marine alkaloids containing pyrrole, oxazole, phenol ring units and differ in the number and positions of chlorine atoms. They are isolated from sea sponges and nudibranchs. In this work, a convenient synthetic method leading to a new phorbazole and its derivatives was developed. This synthesis of the synthetic phorbazole G and its derivatives has been achieved in seven steps in good overall yields of 26-52 %. It involved formation of the pyrrole oxazole skeleton followed by chlorination. The pyrrole oxazole skeleton was synthesized from pyrrole and substituted acetophenones, and the key step was cyclodehydration of the amides to give protected oxazoles, followed by hydrolysis. achieved in seven steps in good overall yields of 26.3 - 52.5 %. It involved formation of the pyrrole oxazole skeleton followed by chlorination. The pyrrole oxazole skeleton was synthesized from pyrrole and substituted acetophenones, and the key step was cyclodehydration of the amides to give protected oxazoles, followed by hydrolysis

Alzheimer's and Parkinson's Disease Novel Therapeutic Target

Thiazolidinedione (TZD) drugs (Takeda Pharmaceuticals and Metabolic Solutions Development Company) targeting inhibition of the mitochondrial pyruvate carrier (MPC) are currently being tested in clinical trials to prevent progression into mild cognitive impairment of Alzheimer's disease (AD) or in the pipeline to prevent neurodegeneration in Parkinson's disease (PD). These have Ki values in the µM range. This study was focused on identifying candidate drug precursors of the natural cinnamic acid products that might have good bioavailability in the nM ranges forming covalent thiol bonds with targets. In silico protein homology modeling and ligand docking has demonstrated that binding cysteine residues within the transport channel is a key part of the inhibitory mechanism. These are covalent thiohemiacetal bonds with the alpha-carbon, carboxylate group, off a phenol ring. Like the classic MPC inhibitors, these natural derivatives of hydroxycinnamic acid have a conjugated pi-system used to form thiol bonds with the cysteine residue via Michael addition.

Crystal structure, Hirshfeld surface analysis and DFT studies of (E)-4-methyl-2-{[(2-methyl-3-nitrophenyl)imino]methyl}phenol

The title compound, C15H14N2O3, was prepared by condensation of 2-hydroxy-5-methyl-benzaldehyde and 2-methyl-3-nitro-phenylamine in ethanol. The configuration of the C=N bond is E. An intramolecular O—H...N hydrogen bond is present, forming an S(6) ring motif and inducing the phenol ring and the Schiff base to be nearly coplanar [C—C—N—C torsion angle of 178.53 (13)°]. In the crystal, molecules are linked by C—H...O interactions, forming chains along the b-axis direction. The Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from H...H (37.2%), C...H (30.7%) and O...H (24.9%) interactions. The gas phase density functional theory (DFT) optimized structure at the B3LYP/ 6–311 G(d,p) level is compared to the experimentally determined molecular structure in the solid state. The HOMO–LUMO behaviour was elucidated to determine the energy gap.

Crystal structure and Hirshfeld surface analysis of 2-{[(4-iodophenyl)imino]methyl}-4-nitrophenol

The title compound, C13H9IN2O3, was synthesized by a condensation reaction between 2-hydroxy-5-nitrobenzaldehyde and 4-iodoaniline, and crystallizes in the orthorhombic space group Pna21. The 4-iodobenzene ring is inclined to the phenol ring by a dihedral angle of 39.1 (2)°. The configuration about the C=N double bond is E. The crystal structure features C—H...O hydrogen-bonding interactions. A Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the packing arrangement are O...H/H...O (26.9%) and H...H (22.0%) interactions.

Highly Crosslinked Polybenzoxazines from Monobenzoxazines: The Effect of Meta-Substitution in the Phenol Ring

It is possible to control the crosslink density of polymers derived from monobenzoxazines by switching the type of substituents in the phenolic ring and their relative position with respect to the phenol group. We prepared several substituted monobenzoxazines in the para and meta positions of the phenolic ring and studied how these substituents affected the polymerization temperature of monomers and the thermal stability of the final polymers and, more extensively, how they affected the crosslink network of the final polymers. Gel content and dynamic mechanical analysis confirm that ortho- and para-orienting substituents in the meta position generate highly crosslinked materials compared to para ones. This fact can lead to the design of materials with highly crosslinked networks based on monobenzoxazines, simpler and more versatile monomers than the commercial bisbenzoxazines currently in use.

Bis{4-[(2-hydroxy-5-methoxy-3-nitrobenzylidene)amino]phenyl} ether

The molecule of the title compound, C28H22N4O9, exhibits crystallographically imposed twofold rotational symmetry, with a dihedral angle of 66.0 (2)° between the planes of the two central benzene rings bounded to the central oxygen atom. The dihedral angle between the planes of the central benzene ring and the terminal phenol ring is 4.9 (2)°. Each half of the molecule exhibits an imine E configuration. An intramolecular O—H...N hydrogen bond is present. In the crystal, the molecules are linked into layers parallel to the ab plane via C—H...O hydrogen bonds. The crystal studied was refined as a two-component pseudomerohedral twin.

Self-assembled supramolecular structures of O,N,N′ tridentate imidazole–phenol Schiff base compounds

Three imidazole-derived Schiff base compounds comprising an N-methyl imidazole group coupled to a phenol ring through an imine bond were synthesised. The solid state and solution state supramolecular structures as well as energetics are explored.

Topical Application of 7,3′,4′-Trihydroxyisoflavone Alleviates Atopic Dermatitis-Like Symptoms in NC/Nga Mice

Atopic dermatitis is a skin disease characterized by chronic inflammatory lesions, and new therapies are needed to address its rising prevalence. Soy isoflavone has been highlighted as a potential new cosmeceutical material that may have applications in atopic dermatitis care. We have developed a technique to attach an additional -OH group to the ortho position of -OH in the phenol ring using a special enzyme. By adding the -OH group to daidzein, 7,3′,4′-trihydroxyisoflavone can be generated for possible use as a cosmeceutical and functional food material. In this study, we sought to examine the anti-atopic effects of 7,3′,4′-trihydroxyisoflavone, an analog of daidzein. Topical application of 7,3′,4′-trihydroxyisoflavone reduced Dermatophagoides farina extract-induced atopic dermatitis symptoms in NC/Nga mice. Histological analysis demonstrated that 7,3′,4′-trihydroxyisoflavone suppressed D. farina extract-induced infiltration of eosinophils and mast cells into skin lesions. We also found that 7,3′,4′-trihydroxyisoflavone significantly reduces the D. farina extract-induced increases in serum IgE and macrophage-derived chemokine (CCL22) levels. We observed that 7,3′,4′-trihydroxyisoflavone suppresses atopic markers including macrophage-derived chemokine (CCL22) and thymus and activation-regulated chemokine (CCL17) in HaCaT cells. 7,3′,4′-Trihydroxyisoflavone also reduced TNF-α/IFN-γ-induced phosphorylation of ERK1/2 and JNK1/2. These results highlight several desirable properties of 7,3′,4′-trihydroxyisoflavone, which support its use as a cosmeceutical ingredient for the treatment of atopic dermatitis.

(E)-1-(2-Hydroxy-6-methoxyphenyl)-3-(2-methoxynaphthalen-1-yl)prop-2-en-1-one

In the title compound, C21H18O4, the dihedral angle between the naphthelene ring system (r.m.s. deviation = 0.014 Å) and the benzene ring is 9.68 (1)°. The C atom of the methoxy group of the naphthalene ring system is almost coplanar with the ring [C—O—C—C = −2.0 (3)°], whereas the C atom of the methoxy group of the phenol ring is slightly twisted [C—O—C—C = 6.2 (3)°]. An intramolecular O—H...O hydrogen bond generates an S(6) ring motif.