Trans‐iso‐α‐acid is one of the main contributors to the bitter taste of fresh beer and is known to transform into various derivatives during beer aging. However, structural characterization of the ...derivatives has been a challenging task because of the formation of too many components. Herein, we report that most of the transformation products of trans‐iso‐α‐acid, isolated in this study in only small quantities by HPLC, can be structurally analyzed with the crystalline sponge method. Thirteen compounds, including eight that were previously unreported, have been successfully isolated and analyzed with complete assignment of their absolute configuration. This provides an improved understanding of the chemical transformations that occur during beer aging.
Beer taste of your favorite is blendable! Comprehensive identification of derivatives from trans‐iso‐α‐acid, derived from one of the most abundant secondary metabolites in hops, was achieved by the HPLC‐assisted crystalline sponge method. Thirteen components, including previously unknown eight, were fully characterized, promising the development of new, advanced brewing technology for controlling the bitter components of beer.
Inflammation in the brain is associated with various disorders including Alzheimer's disease and depression. Thus, inflammation has received increasing attention regarding preventive approaches to ...such disorders. Epidemiological investigations have reported that drinking tea reduces the risk of dementia and depression. Theaflavins, a polyphenol found in black tea, are known to have anti-oxidative and anti-inflammation effects, but the effects of theaflavins on cognitive decline and depression induced by inflammation have not been investigated. To address this research gap, the present study assessed whether theaflavins could protect synapses and dendrites damaged by inflammation and prevent concomitant memory impairment and depression-like behavior in mice. Intracerebroventricular injection with lipopolysaccharide (LPS) induces neural inflammation associated with reduced spontaneous alternations in the Y-maze test and increased immobility in the tail suspension test, indicating impaired spatial memory and depression-like behavior, respectively. Oral administration with theaflavins prevented these behavioral changes induced by LPS. Theaflavins also suppressed productions of inflammatory cytokines and prevented dendritic atrophy and spine loss in the brain. Notably, theaflavins have a stronger anti-inflammatory effect than other polyphenols such as catechin, chlorogenic acid, and caffeic acid. These results suggest that theaflavins can suppress neural inflammation and prevent the symptoms of inflammation-related brain disorders.
The crystalline sponge (CS) method allows structural elucidation of a target compound (guest) in solution by single crystal X‐ray diffraction through trapping the guest into the CS framework. In ...principle, the CS method is inapplicable to reactive compounds that break the CS framework, such as acidic, basic, or nucleophilic ones. Here, a solution to this problem is disclosed wherein an ion pair of the guest compound is formed during the guest‐soaking step by adding a suitable reagent. The ion pair can be observed and does not damage the CS framework. Using the developed method, amino, guanidino, and amidino compounds have been successfully analyzed as ion pairs with sulfonic acids. Practical utility has been shown because the absolute configurations of optically resolved amine derivatives were revealed with only a few micrograms. This demonstrates that the ion‐pair‐soaking method is simple and expands the range of compounds applicable to the CS method.
A significant limitation of the crystalline sponge (CS) method, such that reactive ionizable compounds are inapplicable for the method due to destruction of the CS host frameworks, has been resolved. Simply adding a suitable reagent to the solution during the analyte‐soaking step facilitates ion pair formation, enabling observation of the analyte structure as ion pairs without damage to the CS host frameworks.
Rice (Oryza sativa L.) plants accumulate antimicrobial compounds known as phytoalexins in response to pathogen attack. To date, more than 20 compounds have been isolated as phytoalexins from rice, ...mostly diterpenoids. However, the quantitative analysis of diterpenoid phytoalexins in various cultivars has revealed that the cultivar ‘Jinguoyin’ does not accumulate these compounds at detectable concentrations. Therefore, in this study, we attempted to detect a new class of phytoalexins from Bipolaris oryzae infected leaves of ‘Jinguoyin’. We detected five compounds in the leaves of the target cultivar, whereas these compounds were not detected in the leaves of ‘Nipponbare’ or ‘Kasalath’, which are representative cultivars of the japonica and indica subspecies. Subsequently, we isolated these compounds from ultraviolet (UV)-light-irradiated leaves and determined their structures by spectroscopic analysis and the crystalline sponge method. All the compounds were diterpenoids containing a benzene ring and were detected from the pathogen-infected rice leaves for the first time. Because the compounds showed antifungal activity against B. oryzae and Pyricularia oryzae, we propose that they function as phytoalexins in rice and named them abietoryzins A–E. The abietoryzins tended to accumulate at high concentrations in cultivars that accumulated low levels of known diterpenoid phytoalexins after UV-light irradiation. Of the total of 69 cultivars in the WRC, 30 cultivars accumulated at least one of the abietoryzins, and, in 15 cultivars, the amounts of some abietoryzins were the highest among those of the analyzed phytoalexins. Therefore, abietoryzins are a major phytoalexin group in rice, although their presence has, to date, been overlooked.
Undescribed diterpenoids, abietoryzins, were identified in rice leaves infected by Bipolaris oryzae. Abietoryzins are one of the major classes of diterpenoids phytoalexins in rice. Display omitted
•Undescribed diterpenoids, abietoryzins, were identified in rice.•Abietoryzins serve as phytoalexins.•Abietoryzins are one of the major classes of diterpenoid phytoalexins in rice leaves.
Fungal meroterpenoids are a diverse group of hybrid natural products with impressive structural complexity and high potential as drug candidates. In this work, we evaluate the promiscuity of the ...early structure diversity‐generating step in fungal meroterpenoid biosynthetic pathways: the multibond‐forming polyene cyclizations catalyzed by the yet poorly understood family of fungal meroterpenoid cyclases. In total, 12 unnatural meroterpenoids were accessed chemoenzymatically using synthetic substrates. Their complex structures were determined by 2D NMR studies as well as crystalline‐sponge‐based X‐ray diffraction analyses. The results obtained revealed a high degree of enzyme promiscuity and experimental results which together with quantum chemical calculations provided a deeper insight into the catalytic activity of this new family of non‐canonical, terpene cyclases. The knowledge obtained paves the way to design and engineer artificial pathways towards second generation meroterpenoids with valuable bioactivities based on combinatorial biosynthetic strategies.
Fungal meroterpenoid cyclases, a recently discovered family of membrane‐integrated terpene cyclases, have been exploited as tools for the synthesis of second generation meroterpenoid natural products. The results demonstrate a broad substrate tolerance leading to several new meroterpenoid scaffolds. DFT calculations provided insights into the mechanism of enzyme‐mediated polyene cyclizations.
The bitter taste of beer originates from resins in hops (Humulus lupulus L.), which are classified into two subtypes (soft and hard). Whereas the nature and reactivity of soft-resin-derived ...compounds, such as α-, β-, and iso-α-acids, are well studied, there is only a little information on the compounds in hard resin. For this work, hard resin was prepared from stored hops and investigated for its compositional changes in an experimental model of beer aging. The hard resin contained a series of α-acid oxides. Among them, 4′-hydroxyallohumulinones were unstable under beer storage conditions, and their transformation induced primary compositional changes of the hard resin during beer aging. The chemical structures of the products, including novel polycyclic compounds scorpiohumulinols A and B and dicyclohumulinols A and B, were determined by HRMS and NMR analyses. These compounds were proposed to be produced via proton-catalyzed cyclization reactions of 4′-hydroxyallohumulinones. Furthermore, they were more stable than their precursor 4′-hydroxyallohumulinones during prolonged storage periods.
The bitter acids in hops (Humulus lupulus L.) and beer, such as α-, β-, and iso-α-acids, are known to affect beer quality and display various physiological effects. However, these compounds readily ...oxidize, and the effect of the oxides on the properties of beer or their potential health benefits are not well understood. In this study, we developed a simple preparative method for the bitter acid oxide fraction derived from hops and designated the constituents as matured hop bitter acids (MHBA). HPLC-PDA-ESI/HRMS and MS(2) revealed that MHBA are primarily composed of α-acid-derived oxides, which possess a common β-tricarbonyl moiety in their structures similar to α-, β-, and iso-α-acids. We also developed a quantitative analytical method of whole MHBA by HPLC, which showed high precision and reproducibility. Using our newly developed method, the concentration of whole MHBA in several commercial beers was evaluated. Our results will promote the study of bitter acid oxides.
A biomimetic route to farnesyl pyrophosphate and dimethyl orsellinic acid (DMOA)‐derived meroterpenoid scaffolds has yet to be reported despite great interest from the chemistry and biomedical ...research communities. A concise synthetic route with the potential to access DMOA‐derived meroterpenoids is highly desirable to create a library of related compounds. Herein, we report novel dearomatization methodology followed by polyene cyclization to access DMOA‐derived meroterpenoid frameworks in six steps from commercially available starting materials. Furthermore, several farnesyl alkene substrates were used to generate structurally novel, DMOA‐derived meroterpenoid derivatives. DFT calculations combined with experimentation provided a rationale for the observed thermodynamic distribution of polycyclization products.
Regioselective dearomatization of 3,5‐dimethylorsellinic acid (DMOA) provides rapid access to a key dearomatized intermediate in the biosynthetic pathway of DMOA‐derived meroterpenoids. This intermediate undergoes polycyclization under Lewis acid mediation to provide meroterpenoid scaffolds. Several structurally novel meroterpenoids were obtained by termination via either C‐ or O‐cyclization.
Abstract Objective The effects of certain tea components on the prevention of obesity in humans have recently been reported, although it is still unclear whether black tea consumption is beneficial. ...We obtained black tea extract (BTPE) consisting of polyphenols specific to black tea, and from it, prepared a polymerized polyphenol fraction (BTP). The effectiveness of oral administration of the BTPE was examined in in vitro and in vivo experiments. Methods Effects of BTPE or BTP on pancreatic lipase activity were investigated in vitro. Male Wistar rats were administered an oral lipid emulsion containing BTPE at a concentration of 500 or 1000 mg/kg body weight and sequential plasma lipid levels were measured. Female C57BL/6N mice were fed a standard or high-fat diet supplemented with 1% or 5% (w/w) BTPE for 8 wk and changes in body weight were examined. Results BTP and BTPE inhibited pancreatic lipase activity with an IC50 of 15.5 and 36.4 μg/mL in vitro, respectively. BTPE suppressed increases in rat plasma triglyceride levels in a dose-dependent manner after oral administration of a lipid emulsion. Furthermore, administration of the 5% BTPE suppressed increases in body weight ( P < 0.05), parametrial adipose tissue mass, and liver lipid content (reduced to 56.9% and 81.7% of control mice, respectively, P < 0.05) in mice fed a high-fat diet. Conclusion The BTPE may prevent diet-induced obesity by inhibiting intestinal lipid absorption. It was suggested that the major active component in the BTPE was BTP.
Improving and maintaining memory function is effective in preventing cognitive decline and dementia. Previously, we demonstrated that iso-α-acids, the hop-derived bitter components in beer, prevent ...cognitive impairment in an Alzheimer's disease mouse model. In this report, we investigated the effects of matured hop bitter acids (MHBA) containing components of oxides derived from α- and β-acids, and structurally similar to iso-α-acids, on cognitive function using behavioral pharmacological procedures. MHBA and the representative components of MHBA, 4'-hydroxyallohumulinone (HAH) and 4'-hydroxy-cis-alloisohumulone (HAIH) improved spatial working memory in scopolamine-induced amnesia mice. MHBA also enhanced episodic memory in the novel object recognition test (NORT). The administration of MHBA increased the amount of norepinephrine (NE) and NE release into cerebrospinal fluid (CSF) in hippocampus. The MHBA activity in improving memory function was attenuated by treatment with a β-adrenergic receptor inhibitor. In addition, vagotomized mice did not display the memory improvement induced by MHBA. Together, our results suggest that MHBA improves memory function via stimulation of the vagus nerve and enhancement of NE release in the hippocampus. Vagus nerve activation by the intake of food materials including MHBA may be a safe and effective approach for improving cognitive function.
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