Plant Development in the Garden Pea as Revealed by Mutations in the Crd/PsYUC1 Gene.

In common with other plant species, the garden pea (Pisum sativum) produces the auxin indole-3-acetic acid (IAA) from tryptophan via a single intermediate, indole-3-pyruvic acid (IPyA). IPyA is converted to IAA by PsYUC1, also known as Crispoid (Crd). Here, we extend our understanding of the developmental processes affected by the Crd gene by examining the phenotypic effects of crd gene mutations on leaves, flowers, and roots. We show that in pea, Crd/PsYUC1 is important for the initiation and identity of leaflets and tendrils, stamens, and lateral roots. We also report on aspects of auxin deactivation in pea.

Distinctive Arbutin-Containing Markers: Chemotaxonomic Significance and Insights into the Evolution of Proteaceae Phytochemistry.

Natural products isolation studies of eight endemic Tasmanian Proteaceae species - Agastachys odorata, Persoonia juniperina, Hakea megadenia, Hakea epiglottis, Orites diversifolius, Orites acicularis, Orites revolutus, and Telopea truncata - and three endemic Australian Proteaceae species Banksia serrata, Banksia praemorsa, and Banksia marginata were undertaken. Two previously unreported glycoside-derived natural products were identified, in addition to four other tremendously rare arbutin esters. The results of this study provide further evidence consistent with the proposal that these distinctive arbutin esters represent markers that can provide valuable insights into the chemical evolution of plant species within the family Proteaceae.

Furanosesquiterpenes and Related Natural Products from Myoporum Species: Isolation and Semisynthesis.

Myoporum species are recognized as toxic plants. Essential oils from the leaves of these species contain furanosesquiterpenes, which comprise the active toxins. In this report, natural products isolation studies of three Myoporum species (M. insulare, M. parvifolium, and M. montanum) afforded two previously unreported furanosesquiterpenes (24 and 25) and three unprecedented γ-lactone-containing analogues (26-28), along with nine previously reported furanosesquiterpenes and five other natural products. Among the 14 furanosesquiterpenes and related compounds isolated in this study, we observed three distinct types of furanosesquiterpene structures isolated from each of these Myoporum species. Semisyntheses of four sesquiterpene natural products were completed from (-)-ngaione over two steps in each case. This included the synthesis of the lactam-containing sesquiterpene myoporumine A.

Revising the taxonomic placement of Laetiporus persicinus within the Laetiporaceae.

The fungus currently known as Laetiporus persicinus is a recognizable brown-rot decayer that is widespread on oak hosts in the southeastern United States. This species was first described as Polyporus persicinus in 1872 based on collections by Henry W. Ravenel from South Carolina. In this study, we elucidate the phylogenetic relationships of Laetiporus persicinus based on maximum likelihood and Bayesian inference analyses of a four-locus data set (18S, 28S, rpb2, and tef1) from taxa within the Fomitopsidaceae and Laetiporaceae. The internal transcribed spacer (ITS) region was analyzed separately because it was not possible to align this locus across a diverse data set that included taxa from multiple families. Our analysis and previous studies indicate that Laetiporus persicinus does not belong to Laetiporus sensu stricto, and we found a strongly supported relationship between Laetiporus persicinus and the African species Kusaghiporia usambarensis, despite the fact that the 28S phylogeny resolved a different (but unsupported) topology. Here, we propose Kusaghiporia persicinus, comb. nov., based on a combination of morphological and molecular data. Laetiporus persicinus shares many morphological features with K. usambarensis that are missing in other Laetiporus species, including centrally stipitate basidiomata, a brown to pinkish pileus surface, and a pore layer that bruises when touched. However, K. usambarensis and L. persicinus differ in basidiospore size and shape as well as their geographic distributions. We provide a revised taxonomic treatment for this common wood-decay fungus.

Strategies for the synthesis of Stemona alkaloids: an update.

Covering: 2009 to 2022The Stemona alkaloids, which are found in plant species from the family Stemonaceae, represent a tremendously large and structurally-diverse family of natural products. This review presents and discusses a selection of case studies, grouped by alkaloid class, that showcase the key strategies and overall progress that has been made in the synthesis of Stemona alkaloids and related compounds since 2009. Structural reassignments that have been reported over this period are also identified where necessary.

Discovery of Periodinane Oxy-Assisted (POA) Oxidation Mechanism in the IBX-Controlled Oxidative Dearomatization of Pyrroles Mediated by Acetic Acid.

The 2-iodoxybenzoic acid (IBX)-controlled oxidative dearomatization of pyrroles occurs very slowly (or not all) in many organic solvents, including DMSO in which IBX is soluble. Interestingly, although IBX is only partially soluble in acetic acid, this solvent mediates the pyrrole oxidative dearomatization. With the aid of density functional theory (DFT) calculations, we have discovered a new mode of reactivity, termed the periodinane oxy-assisted (POA) oxidation mechanism, which explains this observation.

Structural Revision of Parvistemoamide: Informing Biosynthetic Proposals of Stemona Alkaloids.

The natural product parvistemoamide was isolated in 1991 and has ostensibly eluded synthesis. Its distinctive assigned structure represents the first and only Stemona alkaloid within its class. For over 30 years, this structure has influenced biosynthetic proposals concerning this family of natural products. Following synthetic studies and comprehensive analysis of relevant literature, a revised structure of parvistemoamide is proposed that is consistent with the fundamental Stemona alkaloid stemoamide.

Differential Effects of a Novel Opioid Ligand UTA1003 on Antinociceptive Tolerance and Motor Behaviour.

Analgesic tolerance is a major problem in the clinic for the maintenance of opioid-induced long-term pain relief. Opioids with mixed activity on multiple opioid receptors promise reduced antinociceptive tolerance in preclinical studies, but these compounds typically show poor bioavailability upon oral, subcutaneous, intraperitoneal, or intravenous administration. We designed UTA1003 as a novel opioid that acts as a mu (MOP) and kappa (KOP) opioid receptor agonist and a partial agonist for delta (DOP) opioid receptor. In the present study, its antinociceptive effects, as well as its effects on antinociceptive tolerance and motor behaviour, were investigated in male rats. Acute antinociception was measured before (basal) and at different time points after subcutaneous injection of UTA1003 or morphine using the tail flick and hot plate assays. Various motor behavioural activities, including horizontal locomotion, rearing, and turning, were automatically measured in an open-field arena. The antinociceptive and behavioural effects of repeated administration of UTA1003 and morphine were determined over eight days. UTA1003 induced mild antinociceptive effects after acute administration but induced no tolerance after repeated treatment. Importantly, UTA1003 co-treatment with morphine prevented antinociceptive tolerance compared to morphine alone. UTA1003 showed less motor suppression than morphine in both acute and sub-chronic treatment regimens, while it did not affect morphine-induced motor suppression or hyper-excitation. Based on these activities, we speculate that UTA1003 crosses the blood-brain barrier after subcutaneous administration and, therefore, could be developed as a lead molecule to avoid opioid-induced antinociceptive tolerance and motor suppression. Further structural modifications to improve its antinociceptive effects, toxicity profile, and ADME parameters are nevertheless required.

Transcontinental Dispersal of Nonendemic Fungal Pathogens through Wooden Handicraft Imports.

This study examined the viability and diversity of fungi harbored in imported wooden handicraft products sold in six retail stores in Florida, United States. Despite being subjected to trade regulations that require various sterilization/fumigation protocols, our study demonstrates high survival and diversity of fungi in wood products originating from at least seven countries on three continents. Among these fungi were nonendemic plant and human pathogens, as well as mycotoxin producers. Several products that are sold for use in food preparation and consumption harbored a novel (to North America) plant and human pathogen, Paecilomyces formosus. In addition, a high number of species isolated were thermophilic and included halophilic species, suggesting adaptability and selection through current wood treatment protocols that utilize heat and/or fumigation with methyl-bromide. This research suggests that current federal guidelines for imports of wooden goods are not sufficient to avoid the transit of potential live pathogens and demonstrates the need to increase safeguards at both points of origin and entry for biosecurity against introduction from invasive fungal species in wood products. Future import regulations should consider living fungi, their tolerance to extreme conditions, and their potential survival in solid substrates. Mitigation efforts may require additional steps such as more stringent fumigation and/or sterilization strategies and limiting use of wood that has not been processed to remove bark and decay. IMPORTANCE This study, the first of its kind, demonstrates the risk of importation of nonendemic foreign fungi on wooden handicrafts into the United States despite the application of sanitation protocols. Previous risk assessments of imported wood products have focused on potential for introduction of invasive arthropods (and their fungal symbionts) or have focused on other classes of wood products (timber, wooden furniture, garden products, etc.). Little to no attention has been paid to wooden handicrafts and the fungal pathogens (of plants and humans) they may carry. Due to the large size and diversity of this market, the risk for introduction of potentially dangerous pathogens is significant as illustrated by the results of this study.

Synthesis of Pyrrolidine- and γ-Lactam-Containing Natural Products and Related Compounds from Pyrrole Scaffolds.

Polycyclic alkaloid natural products featuring pyrrolidine and pyrrolidinone motifs remain enduring targets of total synthesis endeavors. Pyrrole and its derivatives have been exploited to access many such frameworks, including alkaloids belonging to the Aspidosperma, Stemona, and batzelladine families. In this article, a selection of exemplars that highlight the utility of pyrrole-based approaches to facilitate total syntheses of pyrrolidine- and pyrrolidinone-containing alkaloids and related molecules are showcased.

Natural products isolation studies of the paleoendemic plant species Nothofagus gunnii and Nothofagus cunninghamii.

The first natural product isolation studies of Nothofagus gunnii (Hook.f.) Oerst and Nothofagus cunninghamii (Hook.f.) Oerst have been undertaken. A previously unreported stilbene derivative, pinosylvin monoacetate, was isolated from the leaves of N. gunnii, in addition to 14 known compounds; including the flavonoids galangin, pinobanksin, catechin and quercetin; sesquiterpenoids such as, ilicol and (+)-ß-costol acetate; 2,4-dihydroxy-6-methoxychalcone and pinosylvin. Four known flavonoid natural products, catechin, quercetin, ayanin, and avicularin were isolated from the leaves of N. cunninghamii. This study reveals that N. gunnii is a rich source of flavonoid, chalcone and stilbene compounds, while primarily hydroxyflavonoid compounds are found in N. cunninghamii. The isolated phytochemicals are consistent with the evolutionary relationships suggested to exist among Nothofagus species.

Polygodial and Ophiobolin A Analogues for Covalent Crosslinking of Anticancer Targets.

In a search of small molecules active against apoptosis-resistant cancer cells, including glioma, melanoma, and non-small cell lung cancer, we previously prepared α,ß- and γ,δ-unsaturated ester analogues of polygodial and ophiobolin A, compounds capable of pyrrolylation of primary amines and demonstrating double-digit micromolar antiproliferative potencies in cancer cells. In the current work, we synthesized dimeric and trimeric variants of such compounds in an effort to discover compounds that could crosslink biological primary amine containing targets. We showed that such compounds retain the pyrrolylation ability and possess enhanced single-digit micromolar potencies toward apoptosis-resistant cancer cells. Target identification studies of these interesting compounds are underway.

Exploring Cyclization Strategies to Access Stemona Alkaloids: Subtle Effects Influencing Reactivity in Intramolecular Michael Additions.

This report investigates the fundamental basis for rather surprising patterns of reactivity in Brønsted acid-mediated cyclizations of pyrrole substrates bearing pendant Michael acceptors that were identified during syntheses of Stemona alkaloids. Integrated experimental and theoretical studies reveal the profound influence that substituent effects have on the viability of these transformations. Additionally, we identify that electronic effects, in addition to barrier-lowering secondary orbital interactions within transition states, account for the exclusive preference for 7-endo-trig cyclizations over 6-exo-trig cyclizations.

Short-Chain Naphthoquinone Protects Against Both Acute and Spontaneous Chronic Murine Colitis by Alleviating Inflammatory Responses.

Ulcerative colitis (UC) is characterised by chronic, relapsing, idiopathic, and multifactorial colon inflammation. Recent evidence suggests that mitochondrial dysfunction plays a critical role in the onset and recurrence of this disease. Previous reports highlighted the potential of short-chain quinones (SCQs) for the treatment of mitochondrial dysfunction due to their reversible redox characteristics. We hypothesised that a recently described potent mitoprotective SCQ (UTA77) could ameliorate UC symptoms and pathology. In a dextran sodium sulphate- (DSS-) induced acute colitis model in C57BL/6J mice, UTA77 substantially improved DSS-induced body weight loss, disease activity index (DAI), colon length, and histopathology. UTA77 administration also significantly increased the expression of tight junction (TJ) proteins occludin and zona-occludin 1 (ZO-1), which preserved intestinal barrier integrity. Similar responses were observed in the spontaneous Winnie model of chronic colitis, where UTA77 significantly improved DAI, colon length, and histopathology. Furthermore, UTA77 potently suppressed elevated levels of proinflammatory cytokines and chemokines in colonic explants of both DSS-treated and Winnie mice. These results strongly suggest that UTA77 or its derivatives could be a promising novel therapeutic approach for the treatment of human UC.

Radical scavenging activity and metabolomic profiling study of ylang-ylang essential oils based on high-performance thin-layer chromatography and multivariate statistical analysis.

Ylang-ylang (YY) essential oil (EO) is distilled from the fresh-mature flowers of the Annonaceae family tropical tree Cananga odorata [Lam.] Hook. f. & Thomson, and is widely used in perfume and cosmetic industries for its fragrant character. Herein, two different metabolomic profiles obtained using high-performance thin-layer chromatography (HPTLC), applying different stains, namely 2,2-diphenyl-1-picrylhydrazyl (DPPH·) and p-anisaldehyde, were used for discrimination of 52 YY samples across geographical origins and distillation grades. The first profile is developed using the DPPH· stain based on the radical scavenging activity (RSA) of YY EOs. Results of the HPTLC-DPPH· assay confirmed that RSA of YY EOs is in proportion to the length of distillation times. Major components contributing to the RSA of YY EOs were tentatively identified as germacrene D and α-farnesene, eugenol and linalool, by gas chromatography-mass spectrometry (GC-MS) and GC-flame ionisation detector (GC-FID). The second profile was developed using the general-purpose p-anisaldehyde stain based on the general chemical composition of YY EOs. Untargeted metabolomic discrimination of YY EOs from different geographical origins was performed based on the HPTLC-p-anisaldehyde profiles, followed by principal component analysis (PCA). A discrimination and prediction model for identification of YY distillation grade was developed using PCA and partial least squares regression (PLS) based on binned HPTLC-ultraviolet (254 nm) profiles, which was successfully applied to distillation grade determination of blended YY Complete EOs.

Three novel Ambrosia Fusarium Clade species producing multiseptate "dolphin-shaped" conidia, and an augmented description of Fusarium kuroshium.

The Ambrosia Fusarium Clade (AFC) is a monophyletic lineage within clade 3 of the Fusarium solani species complex (FSSC) that currently comprises 19 genealogically exclusive species. These fungi are known or predicted to be farmed by adult female Euwallacea ambrosia beetles as a nutritional mutualism (Coleoptera: Scolytinae; Xyleborini). To date, only eight of the 19 AFC species have been described formally with Latin binomials. We describe three AFC species, previously known as AF-8, AF-10, and AF-11, based on molecular phylogenetic analysis of multilocus DNA sequence data and comparative morphological/phenotypic studies. Fusarium duplospermum (AF-8) farmed by E. perbrevis on avocado in Florida, USA, is distinguished by forming two morphologically different types of multiseptate conidia and brownish orange colonies on potato dextrose agar (PDA). Fusarium drepaniforme (AF-10), isolated from an unknown woody host in Singapore and deposited as Herb IMI 351954 in the Royal Botanic Gardens, Kew, UK, under the name F. bugnicourtii, is diagnosed by frequent production of multiseptate sickle-shaped conidia. Fusarium papillatum (AF-11), isolated from mycangia of E. perbrevis infesting tea in Kandy, Sri Lanka, forms multiseptate clavate conidia that possess a papillate apical cell protruding toward the ventral side. Lastly, we prepared an augmented description of F. kuroshium (AF-12), previously isolated from the heads or galleries of E. kuroshio in a California sycamore tree, El Cajon, California, USA, and recently validated nomenclaturally as Fusarium. Conidia formed by F. kuroshium vary widely in size and shape, suggesting a close morphological relationship with F. floridanum, compared with all other AFC species. Maximum likelihood and maximum parsimony analyses of a multilocus data set resolve these three novel AFC species, and F. kuroshium, as phylogenetically distinct based on genealogical concordance. Given the promiscuous nature of several Euwallacea species, and the overlapping geographic range of several AFC species and Euwallacea ambrosia beetles, the potential for symbiont switching among sympatric species is discussed.

Revised Structures of Dehydrostenines A and B: Total Syntheses of (±)-Dehydrostenine A and Structure Assigned to Dehydrostenine B.

The first total syntheses of the Stemona alkaloid dehydrostenine A and the structure assigned to dehydrostenine B have been completed from a simple pyrrole substrate in 10 and 11 steps, respectively. Two independent Brønsted-acid-mediated intramolecular Michael additions were exploited to construct the tetracyclic dehydrostenine core. As a result of synthetic studies and associated analysis of the relevant literature, revisions of the structures originally assigned to dehydrostenines A and B are proposed.

Asperuloside Enhances Taste Perception and Prevents Weight Gain in High-Fat Fed Mice.

Asperuloside is an iridoid glycoside found in many medicinal plants that has produced promising anti-obesity results in animal models. In previous studies, three months of asperuloside administration reduced food intake, body weight, and adipose masses in rats consuming a high fat diet (HFD). However, the mechanisms by which asperuloside exerts its anti-obesity properties were not clarified. Here, we investigated homeostatic and nutrient-sensing mechanisms regulating food intake in mice consuming HFD. We confirmed the anti-obesity properties of asperuloside and, importantly, we identified some mechanisms that could be responsible for its therapeutic effect. Asperuloside reduced body weight and food intake in mice consuming HFD by 10.5 and 12.8% respectively, with no effect on mice eating a standard chow diet. Fasting glucose and plasma insulin were also significantly reduced. Mechanistically, asperuloside significantly reduced hypothalamic mRNA ghrelin, leptin, and pro-opiomelanocortin in mice consuming HFD. The expression of fat lingual receptors (CD36, FFAR1-4), CB1R and sweet lingual receptors (TAS1R2-3) was increased almost 2-fold by the administration of asperuloside. Our findings suggest that asperuloside might exert its therapeutic effects by altering nutrient-sensing receptors in the oral cavity as well as hypothalamic receptors involved in food intake when mice are exposed to obesogenic diets. This signaling pathway is known to influence the subtle hypothalamic equilibrium between energy homeostasis and reward-induced overeating responses. The present pre-clinical study demonstrated that targeting the gustatory system through asperuloside administration could represent a promising and effective new anti-obesity strategy.

Unified Total Syntheses of (±)-Sessilifoliamides B, C, and D.

The first total syntheses of the Stemona alkaloids sessilifoliamides B and D and the second synthesis of sessilifoliamide C have been completed from a simple pyrrole substrate. The bicyclic lactam core was prepared on a gram scale via a Brønsted acid mediated cyclization and controlled oxidation with Dess-Martin periodinane. This delivered sessilifoliamide C (and its C-11 epimer) in 24% yield over 11 steps, and sessilifoliamides B and D in 13 and 17 steps, respectively.