Structural Revision Research Articles

Concise total synthesis and structure revision of metacridamides A and B.

Concise total synthesis of metacridamides A and B was accomplished through repetitive vinylogous Mukaiyama aldol reactions and ynamide-mediated macrolactonization. Spectral data of both synthetic products were identical to those of the natural products, resulting in the revision of the absolute configuration of the C-9 position to be S.

Remote electronic effect on the N-heterocyclic carbene-catalyzed asymmetric intramolecular Stetter reaction and structural revision of products.

The remote electronic effects of chiral N-heterocyclic carbene catalysts on the asymmetric intramolecular Stetter reaction are investigated. The reaction rate and enantioselectivity were markedly influenced by a substituent at a remote position of the catalyst. The absolute configurations of the products are revised on the basis of X-ray diffraction. Density-functional theory calculations rationalize the improvement of the enantioselectivity using an electron-deficient catalyst.

Asymmetric synthesis of (E)-Secobutanolides: total synthesis and structural revision of (+)-Litseakolide F and G

Asymmetric syntheses of secobutanolide series and Litseakolide F and G were successfully achieved using catalytic MBH reaction and Z → E isomerization. These syntheses revised the absolute configuration of natural (+)-Litseakolide F and G.

Mapping Approaches to Decolonizing and Indigenizing the Curriculum at Canadian Universities

This article identifies five predominant approaches to Indigenizing the curriculum occurring within Canadian universities today. Examining these approaches in relation to theories of change articulated by Gaudry and Lorenz (2018) and Stein (2020), the article considers the possibilities and limits of each approach as well as the degree to which they challenge the colonial and Eurocentric edifices of Canadian universities. While many of the current approaches to curricular change involve minor reforms that focus on individual transformation rather than substantive structural shifts, the authors also identify promising initiatives that push toward greater Indigenous intellectual sovereignty and institutional autonomy. The article concludes by calling on academic institutions to better center Indigenous Peoples, lands and knowledges in curricular change, and more specifically, to embrace structural revision that ensures Indigenous leadership and autonomy.

Synthesis and Structural Revision of (±)-6,11-Epoxyisodaucane

Synthesis and Structural Revision of (±)-6,11-Epoxyisodaucane

HSQC-based small molecule accurate recognition technology discovery of diverse cytotoxic sesquiterpenoids from Elephantopus tomentosus L. and structural revision of molephantins A and B

Elephantopus tomentosus L. is a perennial herb taxonomically belonging to the family Asteraceae, which has been used as a folk medicine for the treatment of hepatobiliary diseases. Sesquiterpenoids from this plant have broad biological activities, including anti-tumor, anti-inflammatory, and antibacterial effects. In this study, fifteen structurally diverse sesquiterpenoids comprised 11 germacrane-type and 4 eudesmane-type sesquiterpenoids were prioritized to isolated from Elephantopus tomentosus L. based on the HSQC-based Small Molecule Accurate Recognition Technology (SMART) strategy. Among them, ten sesquiterpenoids were previously unreported, and their structures were elucidated by spectroscopic data, computational methods, single-crystal X-ray diffraction crystallographic data or electronic circular dichroism calculations. In addition, the structures of two known sesquiterpenoids, molephantin A and B, which were reported to possess E-geometry for the Δ1(10) double bond, were revised by reanalyzing their spectroscopic and X-ray crystallographic data. Some sesquiterpenoids exhibited significant cytotoxic activities against Hep3B and HepG2 cell lines.

Total Synthesis of Atrachinenins A and B.

Inspired by a new biosynthetic hypothesis, we report a biomimetic total synthesis of atrachinenins A and B that explains their racemic nature. The synthesis exploits an intermolecular Diels-Alder reaction between a quinone meroterpenoid and E-β-ocimene, followed by intramolecular (3 + 2) cycloaddition and a late-stage aerobic oxidation. Divergent transformations of a simple model system gave several complex polycyclic scaffolds, while also suggesting a structure revision for atrachinenin C.

COX-2 and iNOS inhibitory epimeric meroterpenoids from Ganoderma cochlear and structure revision of cochlearol Q

Four novel epimeric meroterpenoids, ganadone A (1), 3′,10′-di-epi-ganadone A (2), 10′-epi-ganadone A (3), and 3′-epi-ganadone A (4) as well as another pairs of epimers, ganadone B (5) and 10′-epi-ganadone B (6), with a same basic skeleton compound ganadone C (7), together with two lactonized meroterpenoids, ganadones D and E (8 and 9) were isolated from the fruiting bodies of Ganoderma cochlear. Compounds 1–7 were constructed with fascinating adjacent 6′,7′-bifuran ring system. Fortunately, we have revised our previously reported structure cochlearol Q, which was proposed pyrano[6′,7′-b]pyran ring system into 6′,7′-bifuran motif. All the isolates were characterized by analysis of HRESIMS, NMR spectroscopy and 1 was supported by X-ray crystallography analysis. The absolute stereochemistry of 1–9 were assigned by quantum chemical calculations. Biological evaluation of 1–9 showed that 5, 6, and 9 have significant anti-inflammatory potentials.

Total synthesis of (−)-ribesin B and its structural revision

A highly symmetric dihydrofuran lignan, ribesin B (1), isolated from the leaves of Ribes nigrum, was synthesized via a process whereby the key step was a sequential Michael addition–carbocyclization. However, the NMR spectral features of the synthesized 1 were inconsistent with those of the natural product 1. Thus, the chemical synthesis of the isovanillin-moiety containing compound 2 from chiral propargyl alcohol was conducted through a process that included lipase-catalyzed kinetic resolution. The NMR spectrum of 2 was perfectly superimposable to that of naturally isolated ribesin B. Consequently, the structure of ribesin B was revised to be that of 2.

Revision of Internal Structure and Ordering of the Qurʼānic Sūras 105 al–Fīl and 106 Quraysh: Structural and Rhetorical Analysis

The article analyses two suras of the Qur’an (Q. 105 and Q. 106) within the scope of the hypothesis that they initially constituted a textual unity. This assumption was presented by some reports of early Muslim traditions. Several modern researchers also mentioned the thematic coherence of these two suras. Structural analysis of the rhyming endings in both suras and distribution of their thematic units give new insights about supposed previous initial composition of the text. Rhetorical side of the revelation was also analysed according to the concept of emotional plots. These new arguments reinforce the idea that Q. 105 and Q. 106 were revealed as one distinctive piece of the Qur’anic text.

Total Synthesis and Structural Revision of Cephalosporolide J

AbstractHerein, we report the first total synthesis of cephalosporolide J, which is a deep sea sediment derived polyketide harboring a unique bicyclo[3.3.0]furanolactone moiety. The adopted synthetic strategy consisted of the alkynylation of γ-lactone with lithium alkynyltrifluoroborate followed by a spiroketalization triggered by hydrogenation of the triple bond. Through this synthesis, the correct structure of cephalosporolide J is shown to be that of the 9-epi stereoisomer of the structure originally proposed.

Spirocyclic polyketides from the marine fungus Talaromyces sp. CX11

Three new spirocyclic polyketides, talaromyacins A – C, were identified from the endophytic fungus Talaromyces sp. CX11. Their structures including absolute configurations were determined by extensive spectroscopic analysis, Snatzke's method and quantum chemical calculations. Talaromyacin A is identical to the known sequoiamonascin A, for which a structural revision is required.

Characterization of hitherto unknown Valsartan photodegradation impurities

A detailed investigation of Valsartan`s light-induced degradation is reported. Based on UPLC-HRMS studies of stressed solutions several degradation pathways are proposed. Some of the proposed structures were obtained by forced degradation experiments. Examination of analytical data including crystal structures allowed for structural revision of one literature-known degradant. In addition, irradiation under aerobic conditions revealed further degradative pathways leading to two previously unknown decomposition products. Mechanistic considerations regarding their origin helped to identify structural weak points of Valsartan under the influence of light.

Measuring Personalization, Embodiment, and Congruence in Online Learning: A Validation Study.

Instructional designs promoting personalization (conversational style and visible author), embodiment (human-like mannerisms and presence), and social and cognitive congruence have been shown to enhance learning. However, measurements of these instructional design features are lacking. The authors sought to develop and validate an instrument to measure personalization, embodiment, and congruence in an online course, collecting evidence of content, internal structure, and relationships with other variables. Through literature review, expert review, and pilot testing, the authors developed a 15-item, 5-domain instrument. Participants completed this instrument along with assessments of motivation (Instructional Materials Motivation Survey and Motivated Strategies for Learning Questionnaire), knowledge, and course satisfaction immediately after a 30-minute online multimedia learning module comprising slides with voiceover and (for some participants) short video clips, from January to April 2021. Participants included pharmacists, physicians, and advanced practice providers at academic and community hospitals. Confirmatory factor analysis (CFA) was used to examine model fit, followed by structural revisions guided by exploratory factor analysis (EFA) and tested in a new CFA using a split-sample approach. The authors evaluated associations between the revised instrument scores and motivation, knowledge, and satisfaction. There were 406 participants. CFA of the original 15-item instrument revealed poor model fit. EFA using 214 randomly selected participants suggested a 2-domain structure. CFA of the revised structure using the other 192 participants revealed good fit for a 9-item, 2-domain instrument: the Congruence-Personalization Questionnaire (CPQ). Linear regression confirmed positive, statistically significant associations for most hypothesized relationships (R 2 ≥ 0.12 and P < .001 for 14 of 18 associations with motivation and satisfaction). Associations with knowledge were weak and nonsignificant (R 2 ≤ 0.004, P > .23). Evidence of content, internal structure, and relationships with other variables support the validity of CPQ scores for measuring personalization and congruence in an online module.

Signaling network model of cardiomyocyte morphological changes in familial cardiomyopathy

Familial cardiomyopathy is a precursor of heart failure and sudden cardiac death. Over the past several decades, researchers have discovered numerous gene mutations primarily in sarcomeric and cytoskeletal proteins causing two different disease phenotypes: hypertrophic (HCM) and dilated (DCM) cardiomyopathies. However, molecular mechanisms linking genotype to phenotype remain unclear. Here, we employ a systems approach by integrating experimental findings from preclinical studies (e.g., murine data) into a cohesive signaling network to scrutinize genotype to phenotype mechanisms. We developed an HCM/DCM signaling network model utilizing a logic-based differential equations approach and evaluated model performance in predicting experimental data from four contexts (HCM, DCM, pressure overload, and volume overload). The model has an overall prediction accuracy of 83.8%, with higher accuracy in the HCM context (90%) than DCM (75%). Global sensitivity analysis identifies key signaling reactions, with calcium-mediated myofilament force development and calcium-calmodulin kinase signaling ranking the highest. A structural revision analysis indicates potential missing interactions that primarily control calcium regulatory proteins, increasing model prediction accuracy. Combination pharmacotherapy analysis suggests that downregulation of signaling components such as calcium, titin and its associated proteins, growth factor receptors, ERK1/2, and PI3K-AKT could inhibit myocyte growth in HCM. In experiments with patient-specific iPSC-derived cardiomyocytes (MLP-W4R;MYH7-R723C iPSC-CMs), combined inhibition of ERK1/2 and PI3K-AKT rescued the HCM phenotype, as predicted by the model. In DCM, PI3K-AKT-NFAT downregulation combined with upregulation of Ras/ERK1/2 or titin or Gq protein could ameliorate cardiomyocyte morphology. The model results suggest that HCM mutations that increase active force through elevated calcium sensitivity could increase ERK activity and decrease eccentricity through parallel growth factors, Gq-mediated, and titin pathways. Moreover, the model simulated the influence of existing medications on cardiac growth in HCM and DCM contexts. This HCM/DCM signaling model demonstrates utility in investigating genotype to phenotype mechanisms in familial cardiomyopathy.

Biosynthetic Elucidation and Structural Revision of Brevione E: Characterization of the Key Dioxygenase for Pathway Branching from Setosusin Biosynthesis.

Brevione E (1) is a fungal hexacyclic meroditerpenoid with unique oxepane and cycloheptenone moieties. In this study, we identified the biosynthetic gene cluster of 1 and elucidated its biosynthetic pathway via heterologous expression of the biosynthetic genes and in vitro enzymatic reactions. Surprisingly, reexamination of the structure of 1 revealed a substituted tetrahydrofuran ring instead of the previously proposed oxepane system. Moreover, we determined that cycloheptenone synthesis involves skeletal rearrangement catalyzed by the α-ketoglutarate-dependent dioxygenase BrvJ. BrvJ is highly homologous to SetK, which engages in the biosynthesis of another fungal metabolite, setosusin, and accepts the same substrate as BrvJ but performs only simple hydroxylation. Finally, we identified the key amino acid residues critical for product selectivity of BrvJ and SetK, providing insight into how the biosynthesis pathways of 1 and setosusin diverge and how fungi diversify natural products.

Biosynthetic Elucidation and Structural Revision of Brevione E: Characterization of the Key Dioxygenase for Pathway Branching from Setosusin Biosynthesis

Brevione E (1) is a fungal hexacyclic meroditerpenoid with unique oxepane and cycloheptenone moieties. In this study, we identified the biosynthetic gene cluster of 1 and elucidated its biosynthetic pathway via heterologous expression of the biosynthetic genes and in vitro enzymatic reactions. Surprisingly, reexamination of the structure of 1 revealed a substituted tetrahydrofuran ring instead of the previously proposed oxepane system. Moreover, we determined that cycloheptenone synthesis involves skeletal rearrangement catalyzed by the α-ketoglutarate-dependent dioxygenase BrvJ. BrvJ is highly homologous to SetK, which engages in the biosynthesis of another fungal metabolite, setosusin, and accepts the same substrate as BrvJ but performs only simple hydroxylation. Finally, we identified the key amino acid residues critical for product selectivity of BrvJ and SetK, providing insight into how the biosynthesis pathways of 1 and setosusin diverge and how fungi diversify natural products.

Structure Revision of the Sesquiterpene Nordine Based on NMR Spectroscopic Analysis and X-ray Crystallography.

Nordine was reported to be an unusual humulene-type macrocyclic sesquiterpenoid that contains an ether-bridged bicyclic ring between C-10 and C-6 with a hydroxy group at position 2. Here, we report the structure revision of nordine based on incongruities found for carbon chemical shifts in the originally proposed structure, in addition to formation of a diacetylated derivative. As expected, a single-crystal X-ray diffraction analysis unambiguously confirmed our proposal that the nordine (1) structure contains an ether-bridged bicyclic ring between C-10 and C-7 and hydroxy groups at C-2 and C-6. Furthermore, the absolute configuration was determined by ECD spectroscopic analysis.

Guaiane-type sesquiterpenoids with various ring skeletons from Daphne bholua uncovered by molecular networking and structural revisions of previously reported analogues

The genus Daphne is a treasure-house of secondary metabolites with various biological effects, which inspired Daphne bholua being fully investigated phytochemically and biologically for the first time. Here, seven undescribed guaiane-type sesquiterpenoids (1–7) along with thirteen known analogues (8–20) were targeted and isolated from D. bholua using molecular networking. Their chemical structure and configurations were established via NMR spectroscopy analysis, NMR and ECD calculations, Snatzke’s method, along with single-crystal X-ray diffraction technique. Moreover, two pairs of sesquiterpene isomers, either with prominent biological properties or with unprecedented skeleton, were revised by means of computer-assisted structure elucidation, chemical shift calculator using deep learning, etc. The inhibitory potentials of all isolates against acetylcholinesterase were evaluated in vitro and in silico.

Structure Revision of Balsamisides A-D and Establishment of an Empirical Rule for Distinguishing Four Classes of Biflavonoids.

Balsamisides A-D (1-4) are anti-inflammatory and neurotrophic biflavonoidal glycosides originally proposed to possess an epoxide functionality at the C-2/C-3 position. However, there are inconsistencies in their 13C NMR chemical shift values with those of previously reported analogs, indicating that reanalysis of NMR data for structures of 1-4 is necessary. Computational methods aided by the DP4+ probability technique and ECD calculations enabled structural reassignment of 1-4 to have a 2,3-dihydro-3-hydroxyfuran (3-DHF) instead of an epoxide. Additionally, two new biflavonoidal glycosides, balsamisides E and F (14 and 18), possessing a 2,3-dihydro-2-hydroxyfuran (2-DHF) and a 1,4-dioxane ring, respectively, were characterized by conventional NMR and MS data analysis as well as DP4+ and ECD methods. Systematic 13C NMR analysis was performed on the four aforementioned classes of biflavonoids with a 2- or 3-DHF, epoxide, or 1,4-dioxane. As a result, diagnostic 13C NMR chemical shift values of C-2/C-3 for rapid determination of these four biflavonoid classes were formulated, and based on this first empirical rule for (bi)flavonoids eight previously reported ones were structurally revised.