Photochemically Induced Aryl Azide Rearrangement: Solution NMR Spectroscopic Identification of the Rearrangement Product

Photolysis of ethyl 3-azido-4,6-difluorobenzoate at room temperature in the presence of oxygen results in the regioselective formation of ethyl 5,7-difluoro-4-azaspiro[2.4]­hepta-1,4,6-triene-1-carboxylate, presumably via the corresponding ketenimine intermediate which undergoes a photochemical four-electron electrocyclization followed by a rearrangement. The photorearrangement product was identified by multinuclear solution NMR spectroscopic techniques supported by DFT calculations

Halogen Bonding: A Powerful Tool for Modulation of Peptide Conformation

Halogen bonding is a weak chemical force that has so far mostly found applications in crystal engineering. Despite its potential for use in drug discovery, as a new molecular tool in the direction of molecular recognition events, it has rarely been assessed in biopolymers. Motivated by this fact, we have developed a peptide model system that permits the quantitative evaluation of weak forces in a biologically relevant proteinlike environment and have applied it for the assessment of a halogen bond formed between two amino acid side chains. The influence of a single weak force is measured by detection of the extent to which it modulates the conformation of a cooperatively folding system. We have optimized the amino acid sequence of the model peptide on analogues with a hydrogen bond-forming site as a model for the intramolecular halogen bond to be studied, demonstrating the ability of the technique to provide information about any type of weak secondary interaction. A combined solution nuclear magnetic resonance spectroscopic and computational investigation demonstrates that an interstrand halogen bond is capable of conformational stabilization of a β-hairpin foldamer comparable to an analogous hydrogen bond. This is the first report of incorporation of a conformation-stabilizing halogen bond into a peptide/protein system, and the first quantification of a chlorine-centered halogen bond in a biologically relevant system in solution

Flemingins G–O, Cytotoxic and Antioxidant Constituents of the Leaves of <i>Flemingia grahamiana</i>

The known flemingins A–C (<b>1</b>–<b>3</b>) and nine new chalcones, named flemingins G–O (<b>4</b>–<b>12</b>), along with deoxyhomoflemingin (<b>13</b>) and emodin (<b>14</b>) were isolated from a leaf extract of <i>Flemingia grahamiana</i>. The isolated chalcones were found to have a geranyl substituent modified into a chromene ring possessing a residual chain, as shown by spectroscopic methods. The leaf extract showed an IC₅₀ value of 5.9 μg/mL in a DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assay. The chalcones flemingins A, B, C, G, and H were active in the DPPH radical scavenging assay (ED₅₀ 4.4–8.9 μM), while flemingins A and C showed cytotoxicity against MCF-7 human breast cancer cells (IC₅₀ 8.9 and 7.6 μM, respectively)

Busseihydroquinones A–D from the Roots of <i>Pentas bussei</i>

Four new naphthohydroquinones, named busseihydroquinones A–D (<b>1</b>–<b>4</b>), along with a known homoprenylated dihydronaphthoquinone (<b>5</b>), were isolated from the CH₂Cl₂/MeOH (1:1) extract of the roots of <i>Pentas bussei</i>. Although the genus <i>Pentas</i> is frequently used by traditional healers for the treatment of malaria, only marginal activities against the chloroquine-sensitive (D6) and the chloroquine-resistant (W2) strains of <i>Plasmodium falciparum</i> were observed for the crude root extract and the isolated constituents of this plant

Naphthalene Derivatives from the Roots of <i>Pentas parvifolia</i> and <i>Pentas bussei</i>

The phytochemical investigation of the CH₂Cl₂/MeOH (1:1) extract of the roots of <i>Pentas parvifolia</i> led to the isolation of three new naphthalenes, parvinaphthols A (<b>1</b>), B (<b>2</b>), and C (<b>3</b>), two known anthraquinones, and five known naphthalene derivatives. Similar investigation of the roots of <i>Pentas bussei</i> afforded a new polycyclic naphthalene, busseihydroquinone E (<b>4</b>), a new 2,2′-binaphthralenyl-1,1′-dione, busseihydroquinone F (<b>5</b>), and five known naphthalenes. All purified metabolites were characterized by NMR and MS data analyses, whereas the absolute configurations of <b>3</b> and <b>4</b> were determined by single-crystal X-ray diffraction studies. The <i>E</i>-geometry of compound <b>5</b> was supported by DFT-based chemical shift calculations. Compounds <b>2</b>–<b>4</b> showed marginal cytotoxicity against the MDA-MB-231 human triple-negative breast cancer cell line with IC₅₀ values ranging from 62.3 to 129.6 μM

Symmetric Halogen Bonding Is Preferred in Solution

Halogen bonding is a recently rediscovered secondary interaction that shows potential to become a complementary molecular tool to hydrogen bonding in rational drug design and in material sciences. Whereas hydrogen bond symmetry has been the subject of systematic studies for decades, the understanding of the analogous three-center halogen bonds is yet in its infancy. The isotopic perturbation of equilibrium (IPE) technique with ¹³C NMR detection was applied to regioselectively deuterated pyridine complexes to investigate the symmetry of [N–I–N]⁺ and [N–Br–N]⁺ halogen bonding in solution. Preference for a symmetric arrangement was observed for both a freely adjustable and for a conformationally restricted [N–X–N]⁺ model system, as also confirmed by computation on the DFT level. A closely attached counterion is shown to be compatible with the preferred symmetric arrangement. The experimental observations and computational predictions reveal a high energetic gain upon formation of symmetric, three-center four-electron halogen bonding. Whereas hydrogen bonds are generally asymmetric in solution and symmetric in the crystalline state, the analogous bromine and iodine centered halogen bonds prefer symmetric arrangement in solution

Naphthalene Derivatives from the Roots of <i>Pentas parvifolia</i> and <i>Pentas bussei</i>

The phytochemical investigation of the CH₂Cl₂/MeOH (1:1) extract of the roots of <i>Pentas parvifolia</i> led to the isolation of three new naphthalenes, parvinaphthols A (<b>1</b>), B (<b>2</b>), and C (<b>3</b>), two known anthraquinones, and five known naphthalene derivatives. Similar investigation of the roots of <i>Pentas bussei</i> afforded a new polycyclic naphthalene, busseihydroquinone E (<b>4</b>), a new 2,2′-binaphthralenyl-1,1′-dione, busseihydroquinone F (<b>5</b>), and five known naphthalenes. All purified metabolites were characterized by NMR and MS data analyses, whereas the absolute configurations of <b>3</b> and <b>4</b> were determined by single-crystal X-ray diffraction studies. The <i>E</i>-geometry of compound <b>5</b> was supported by DFT-based chemical shift calculations. Compounds <b>2</b>–<b>4</b> showed marginal cytotoxicity against the MDA-MB-231 human triple-negative breast cancer cell line with IC₅₀ values ranging from 62.3 to 129.6 μM

Flavonoids from <i>Erythrina schliebenii</i>

Prenylated and <i>O</i>-methylflavonoids including one new pterocarpan (<b>1</b>), three new isoflavones (<b>2</b>–<b>4</b>), and nineteen known natural products (<b>5</b>–<b>23</b>) were isolated and identified from the root, stem bark, and leaf extracts of <i>Erythrina schliebenii</i>. The crude extracts and their constituents were evaluated for antitubercular activity against <i>Mycobacterium tuberculosis</i> (H37Rv strain), showing MICs of 32–64 μg mL^–1 and 36.9–101.8 μM, respectively. Evaluation of their toxicity against the aggressive human breast cancer cell line MDA-MB-231 indicated EC₅₀ values of 13.0–290.6 μM (pure compounds) and 38.3 to >100 μg mL^–1 (crude extracts)

Isoflavones and Rotenoids from the Leaves of <i>Millettia oblata</i> ssp. <i>teitensis</i>

A new isoflavone, 8-prenylmilldrone (<b>1</b>), and four new rotenoids, oblarotenoids A–D (<b>2</b>–<b>5</b>), along with nine known compounds (<b>6</b>–<b>14</b>), were isolated from the CH₂Cl₂/CH₃OH (1:1) extract of the leaves of <i>Millettia oblata</i> ssp. <i>teitensis</i> by chromatographic separation. The purified compounds were identified by NMR spectroscopic and mass spectrometric analyses, whereas the absolute configurations of the rotenoids were established on the basis of chiroptical data and in some cases by single-crystal X-ray crystallography. Maximaisoflavone J (<b>11</b>) and oblarotenoid C (<b>4</b>) showed weak activity against the human breast cancer cell line MDA-MB-231 with IC₅₀ values of 33.3 and 93.8 μM, respectively

Flavonoids from <i>Erythrina schliebenii</i>

Prenylated and <i>O</i>-methylflavonoids including one new pterocarpan (<b>1</b>), three new isoflavones (<b>2</b>–<b>4</b>), and nineteen known natural products (<b>5</b>–<b>23</b>) were isolated and identified from the root, stem bark, and leaf extracts of <i>Erythrina schliebenii</i>. The crude extracts and their constituents were evaluated for antitubercular activity against <i>Mycobacterium tuberculosis</i> (H37Rv strain), showing MICs of 32–64 μg mL^–1 and 36.9–101.8 μM, respectively. Evaluation of their toxicity against the aggressive human breast cancer cell line MDA-MB-231 indicated EC₅₀ values of 13.0–290.6 μM (pure compounds) and 38.3 to >100 μg mL^–1 (crude extracts)