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Non-target screening of veterinary drugs using tandem mass spectrometric data was performed on the SmartMass platform. This newly developed software uses the characteristic fragmentation patterns (CFP) to identify chemicals, especially those containing particular substructures. A mixture of 17 sulfonamides was separated by ultra performance liquid chromatography (UPLC), and SmartMass was used to process the tandem mass spectrometry (MS/MS) data acquired on an Orbitrap mass spectrometer. The data were automatically extracted, and each sulfonamide was recognized and analyzed with a prebuilt analysis rule. By using this software, over 98 % of the false candidate structures were eliminated, and all the correct structures were found within the top 10 of the ranking lists. Furthermore, SmartMass could also be used to identify slightly modified contraband drugs and metabolites with simple prebuilt rules. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Within pharmaceutical research, ensuring the enantiomeric purity of chiral compounds is critical. Specifically, chiral amines are a crucial category of compounds, due to their extensive therapeutic uses. However, the enantiomeric analysis of these compounds, particularly those with significant steric hindrance, remains a challenge. To address this issue, our research introduces a novel chiral 19 F-tagged NNO palladium pincer probe, strategically engineered with an open binding site to accommodate bulky amines. This probe facilitates the enantiodifferentiation of such amines, as evidenced by the distinct 19 F NMR signals generated by the enantiomers. Moreover, our findings highlight the probe's applicability in the chiral discrimination of various psychoactive substances, underscoring its potential for the identification of illegal stimulant use and contributing to forensic investigations.

The surge in applications of nitrile compounds across diverse fields, such as pharmaceuticals, agrochemicals, dyes, and functional materials, necessitates the development of rapid and efficient detection and identification methods. In this study, we introduce a chemosensing strategy employing a novel 19 F-labeled probe, facilitating swift and accurate analysis of a broad spectrum of nitrile-containing analytes. This approach leverages the reversible interaction between the 19 F-labeled probe and the analytes to produce chromatogram-like outputs, ensuring the precise identification of various pharmaceuticals and pesticides within complex matrices. Additionally, this dynamic system offers a versatile platform to investigate through-space 19 F- 19 F interactions, showcasing its potential for future applications in mechanistic studies.

Visible-light-induced decarboxylative trifluoromethylselenolation of (hetero)aromatic carboxylic acids with [Me 4 N][SeCF 3 ], oxidant, and catalysts afforded a variety of (hetero)aryl trifluoromethyl selenoethers in good yields. The reaction might involve a radical process, which generated (hetero)aryl radicals from the stable (hetero)aromatic carboxylic acids via oxidative decarboxylation with NFSI as the oxidant, [di- t Bu-Mes-Acr-Ph][BF 4 ] as the photocatalyst, and 1,1'-biphenyl as the cocatalyst. Both catalysts had a decisive influence on the reaction. The trifluoromethylselenolation was further promoted by the copper salts probably via Cu-mediated cross-coupling of the sensitive SeCF 3 species with the in situ formed (hetero)aryl radicals. Advantages of the method include visible light irradiation, mild reaction conditions at ambient temperature, good functional group tolerance, no pre-functionalization/activation of the starting carboxylic acids, and applicability to drug molecules. This protocol is promising and synthetically useful, which overcame the limitations of the known trifluoromethylselenolation methods and represented the first decarboxylative trifluoromethylselenolation of (hetero)aromatic carboxylic acids.

Cocaine, the archetypal tropane alkaloid from the plant genus Erythroxylum , has recently been used clinically as a topical anesthesia of the mucous membranes. Despite this, the key biosynthetic step of the requisite tropane skeleton (methylecgonone) from the identified intermediate 4-(1-methyl-2-pyrrolidinyl)-3-oxobutanoic acid (MPOA) has remained, until this point, unknown. Herein, we identify two missing enzymes ( En CYP81AN15 and En MT4) necessary for the biosynthesis of the tropane skeleton in cocaine by transient expression of the candidate genes in Nicotiana benthamiana . Cytochrome P450 En CYP81AN15 was observed to selectively mediate the oxidative cyclization of S -MPOA to yield the unstable intermediate ecgonone, which was then methylated to form optically active methylecgonone by methyltransferase En MT4 in Erythroxylum novogranatense . The establishment of this pathway corrects the long-standing (but incorrect) biosynthetic hypothesis of MPOA methylation first and oxidative cyclization second. Notably, the de novo reconstruction of cocaine was realized in N. benthamiana with the two newly identified genes, as well as four already known ones. This study not only reports a near-complete biosynthetic pathway of cocaine and provides new insights into the metabolic networks of tropane alkaloids (cocaine and hyoscyamine) in plants but also enables the heterologous synthesis of tropane alkaloids in other (micro)organisms, entailing significant implications for pharmaceutical production.

A novel diterpenoid, sinueretone A ( 1 ), featuring an unprecedented tricyclo[12.1.0.0 5,9 ]pentadecane carbon framework, along with two new ( 2 and 3 ) and one known ( 4 ) casbane diterpenoids were isolated from the South China Sea soft coral Sinularia erecta . The structures of the new compounds, especially their absolute stereochemistry, were established by extensive spectroscopic analysis, various quantum chemical calculations, and/or X-ray diffraction analyses. A plausible biogenetic relationship of 1 - 4 was proposed, which gave an insight for future biomimetic synthesis of the novel compounds. In a bioassay, compounds 1 and 2 displayed interesting anti-inflammatory activity by the inhibition of lipopolysaccharide-induced tumor necrosis factor-α protein release.

Two novel natural products, beetleane A ( 1 ) and epicoane A ( 2 ), were obtained from the metabolites of an endophytic Epicoccum nigrum . Compound 1 has a unique beetlelike structure that is constructed by the fusion and further fold of an unusual [5.5.5.6]trioxafenestrane with a cycloheptane ring. Compound 2 possesses a compact cagelike structure with a unique 6/5/5/5/6/6/5 heptacyclic ring system. Both 1 and 2 showed strong antiliver fibrosis activity in vitro.

The biosynthetic gene cluster (BGC) for polyether antibiotic K-41A was identified from marine-derived Streptomyces sp. SCSIO 01680 and subjected to combinatorial biosynthetic study. Bioinformatics analyses, gene disruption, and metabolomics analyses afforded eight new derivatives and one known polyether, showcasing five region-specific methyltransferases Pak13, Pak15, Pak20, Pak31, and Pak38 and their respective modification loci. Moreover, bioassays revealed that two disaccharide-bearing polyethers, K-41B and K-41Bm, display enhanced anti-HIV and potent antibacterial activities.

Phytopathogenic fungi have been considered as being an enormous threat in the agricultural system. In our search of new antifungal natural products, nine new halogenated cyclopentenones, bicolorins A-I ( 1-3 , and 5-10 ), along with three known cyclopentenones ( 4 , 11 , and 12 ) were isolated from the endophytic fungus Saccharicola bicolor of Bergenia purpurascens by the one strain-many compounds strategy. Their structures and absolute configurations were elucidated based on extensive spectroscopic analysis, X-ray crystallographic analysis, and time-dependent density functional theory-equivalent circulating density calculations. Compounds 1-12 showed antifungal activities against five phytopathogenic fungi ( Uromyces viciae-fabae , Pythium dissimile , Gibberella zeae , Aspergillus niger, and Sclerotinia sclerotiorum ). Especially, bicolorins B and D ( 2 and 5 ) exhibited strong antifungal activities against P. dissimile with the MIC values of 6.2 and 8.5 μg/mL, respectively, compared with the positive control cycloheximide (MIC of 8.6 μg/mL). Additionally, bicolorin D was proven to be potently antifungal against S. sclerotiorum in vitro and in vivo. This work provides an effective strategy for searching antifungal candidate agents.

A variety of axially chiral biaryldiols were synthesized in good yields with excellent atropo-enantioselectivities through construction of axially chiral indoles catalyzed by asymmetric hydrogen-bond donors. In addition, the new axially chiral compounds were proved to be efficient and practical catalysts for asymmetric catalysis. The strategy not only provides a novel method to synthesize axially chiral compounds but also extends the scope of chiral catalysts.

A challenging problem in natural product discovery is to rapidly dereplicate known compounds and expose novel ones from complicated components. Herein, integrating the LC-MS/MS-dependent molecular networking and 1 H NMR techniques efficiently and successfully enabled the targeted identification of seven new cyclohexadepsipeptides, chrysogeamides A-G (1-7), from the coral-derived fungus Penicillium chrysogenum (CHNSCLM-0003) which was targeted from a library of marine-derived Penicillium fungi. Compound 4 features a rare 3-hydroxy-4-methylhexanoic acid (HMHA) moiety which was first discovered from marine-derived organisms. Interestingly, isotope-labeling feeding experiments confirmed that 13 C 1 -l-Leu was transformed into 13 C 1 -d-Leu moiety, indicating that d-Leu could be isomerized from l-Leu. Compounds 1 and 2 obviously promoted angiogenesis in zebrafish at 1.0 μg/mL with nontoxic to embryonic zebrafish at 100 μg/mL. Combining molecular networking with 1 H NMR as a discovery tool will be implemented as a systematic strategy, not only for known compounds dereplication but also for untapped reservoir discovery.

Two novel nitrogenous diterpenoids, sarinfacetamides A (1) and B (2), featuring an uncommon tricyclo[6.3.1.0 1,5 ]dodecane scaffold, and a known related diterpene (3) were isolated from the South China Sea soft coral Sarcophyton infundibuliforme. Their structures, including the absolute configuration of 1, were established by extensive spectroscopic analysis and TDDFT-ECD calculation. Compounds 1 and 3 exhibited interesting promotion effects on the ConA-induced T lymphocyte proliferation. A plausible biosynthetic pathway for 1 and 2 was also proposed.

An efficient method has been successfully developed to achieve the asymmetric C-H functionalization of indoles in the carbocyclic ring via organocatalysis, and a variety of tetrahydropyranoindoles were synthesized in good yields with excellent stereoselectivities. Further study on thermodynamic calculations indicated that the process was promoted by generating more thermodynamically stable products. This strategy, together with traditional C-3 functionalization of hydroxyindoles, could realize the switchable, regiodivergent asymmetric modification of indoles.

Anthracycline antitumor cytorhodins X and Y feature a rare 9α-glycoside and 7-dexoy-aglycone. Characterization of the cytorhodin gene cluster from Streptomyces sp. SCSIO 1666 through gene inactivations and metabolite analyses reveals three glycosyltransferases (GTs) involved in the sugar tailoring steps. The duo of CytG1 and CytL effects C-7 glycosylation with l-rhodosamine whereas the iterative GT CytG3 and CytW similarly modifies both C-9 and C-10 positions. CytG2 also acts iteratively by incorporating the second and third sugar moiety into the trisaccharide chains at the C-7 or C-10 position.

Artemisians A-D (1-4), the first examples of [4 + 2] Diels-Alder type adducts presumably biosynthesized from a rare 1, 10-4, 5-diseco-guaianolide and a guaianolide diene, along with their possible precursor 5, were isolated from the traditional Chinese medicine Artemisia argyi. The structures of 1-4 were elucidated by extensive spectroscopic analyses and calculated electronic circular dichroism. Compound 2, with an IC 50 value of 3.21 μM, exhibited significant antiproliferative activity via apoptosis induction and G2/M arrest in MDA-MB-468 cells.

The degradation issue of sulfonylurea (SU) has become one of the biggest challenges that hamper the development and application of this class of herbicides, especially in the alkaline soils of northern China. On the basis of the previous discovery that some substituents on the fifth position of the benzene ring in Chlorsulfuron could hasten its degradation rate, apparently in acidic soil, this work on Metsulfuron-methyl showed more convincing results. Two novel compounds (I-1 and I-2) were designed and synthesized, and they still retained potent herbicidal activity in tests against both dicotyledons and monocotyledons. The half-lives of degradation (DT 50 ) assay revealed that I-1 showed an accelerated degradation rate in acidic soil (pH 5.59). Moreover, we delighted to find that the degradation rate of I-1 was 9-10-fold faster than that of Metsulfuron-methyl and Chlorsulfuron when in alkaline soil (pH 8.46), which has more practical value. This research suggests that a modified structure that has potent herbicidal activity as well as accelerated degradation rate could be realized and this approach may provide a way to improve the residue problem of SUs in farmlands with alkaline soil.

Three new diterpenes, xishacorenes A-C, featuring an undescribed bicyclo[3.3.1]nonane nucleus bearing 1-vinyl and 13-[(E)-4-methylpenta-1,3-dien-1-yl] alkyl chains, and a related monocyclic known compound, were isolated from the Xisha soft coral Sinularia polydactyla. The structures of xishacorenes A-C, including their absolute configurations, were elucidated by extensive spectroscopic analysis and TDDFT ECD calculations. The new compounds exhibit an interesting dose-dependent promotion effect on the ConA-induced T lymphocyte proliferation. A plausible biosynthetic pathway of xishacorenes A-C is proposed.

The trifluoromethylcarbene (:CHCF3) was found to be conveniently generated from (2,2,2-trifluoroethyl)diphenyl-sulfonium triflate (Ph2S(+)CH2CF3 (-)OTf), which was successfully applied in Fe-catalyzed cyclopropanation of olefins, giving the corresponding trifluoromethylated cyclopropanes in high yields.

A new method has been developed for the Cu-catalyzed C-H trifluoromethylation of 3-arylprop-1-ynes for the selective construction of allenic Csp(2)-CF3 and propargyl Csp(3)-CF3 bonds. The selective formation of allenic Csp(2)-CF3 and propargyl Csp(3)-CF3 bonds can be controlled by modifying the reaction conditions.

To find novel high-activity and low-toxicity herbicide lead compounds with novel herbicidal mode of action, series of novel α-amino phosphonate derivatives containing a pyrimidinyl moiety, I, II, III, and IV, were designed and synthesized by Lewis acid (magnesium perchlorate) catalyzed Mannich-type reaction of aldehydes, amines, and phosphites. Their structures were clearly identified by spectroscopy data (IR, (1)H NMR, (31)P NMR, EI-MS) and elemental analyses. The bioassay [in vitro, in vivo (GH1 and GH2)] showed that most compounds I exhibited good herbicidal activities; for example, the activities of compounds Ib, Ic, Ig, Ii, Ik, and Im were as good as the positive control herbicides (acetochlor, atrazine, mesotrione, and glyphosate). However, their structural isomers II and III and analogues IV did not display any herbicidal activities in vivo, although some of them possessed selective inhibitory activity against Arabidopsis thaliana in vitro. Interestingly, it was found that compounds IVs, IVt, and IVl showed selective insecticidal activities against Aphis species or Plutella xylostella, respectively. Their preliminary herbicidal mode of action and structure-activity relationships were also studied.

Investigation of the alkaloids from Myrioneuron faberi, a plant unique to China, gave four pairs of enantiomers (1-4). (±)-β-Myrifabral A (1) and (±)-α-myrifabral A (2) formed an inseparable mixture of anomers (cluster A), as did (±)-β-myrifabral B (3) and (±)-α-myrifabral B (4) (cluster B). Their structures were determined by X-ray diffraction and NMR analysis. Compounds 1-4 possessed novel cyclohexane-fused octahydroquinolizine skeletons and represent the first quinolizidine alkaloids from the genus Myrioneuron. The epimers of cluster A (1 and 2) were modified and separated. In vitro, clusters A and B and their derivatives inhibited replication of hepatitis C virus (HCV, IC50 0.9 to 4.7 μM) with cytotoxicity lower than that of telaprevir.

Three new 14-membered resorcylic acid lactones, cochliomycins D-F, 1-3, and eight known analogues, 4-11, were isolated from the sea anemone-derived fungus Cochliobolus lunatus. Compounds 1-4 are diastereomers differing from each other by the absolute configurations of the 4',5'-diol chiral centers. The absolute configurations of 1-4 were established by the CD exciton chirality method and TDDFT ECD calculations. In antifouling assays, 1, 3-6, and 6a exhibited potent antifouling activities against the larval settlement of the barnacle Balanus amphitrite at nontoxic concentrations, with EC 50 values ranging from 1.82 to 22.5 μg/mL. Noticeably, fungicide whole-plant assays indicated that 6 showed excellent activity on the Plasmopara viticola preventative test at 6 ppm and concentration-dependent activity on the Phytophthora infestans preventative application at 200, 60, and 20 ppm. Preliminary structure-activity relationships are also discussed.

One Myrioneuron alkaloid, myrifabine (1), the first example of a dimer with 12 chiral centers embraced in a decacyclic novel skeleton, was isolated from Myrioneuron faberi . Its structure was elucidated by spectroscopic data and single-crystal X-ray diffraction. The antimicrobial and cytotoxic activities of 1 were evaluated in vitro.

An enantioselective cascade Michael-Michael reaction between chalcones enolates and nitromethane catalyzed by a bifunctional thiourea is developed. This reaction provides a mild but efficient approach to chiral benzopyrans bearing three consecutive stereocenters in high yields with excellent stereoselectivities, and the benzopyrans can be easily transformed to the corresponding tricyclic product.

Seven new prieurianin-type limonoids, aphapolynins C-I (1-7), and a new aphanamolide-type limonoid, aphanamolide B (8), along with seventeen known compounds, were isolated from the fruits of Aphanamixis polystachya. The structures of these compounds were established on the basis of spectroscopic studies. The absolute configurations were determined by combination of electronic circular dichroism (ECD) calculation, CD exciton chirality method, and single crystal X-ray diffraction. All these isolates were evaluated for their cytotoxicities against three human cancer cell lines, for their inhibitory effects on lipopolysaccharide (LPS) induced RAW264.7 murine macrophages, and for their fungicidal, herbicidal, and insecticidal activities. Compounds 1, 14, 16, and 17 exhibited significant fungicidal activities; 1 and 25 in particular showed good insecticidal activities. The α,β-unsaturated lactone and 14,15-epoxy ring moieties were essential for the insecticidal activity.

Sclerotiorin 1, first isolated from Penicillium sclerotiorum, has weak antifungal activity and belongs to the azaphilone-type family of natural products. Several series of sclerotiorin analogues were designed and synthesized with the aim of discovering novel fungicides with improved activity. The syntheses involved two key steps, cycloisomerization and then oxidation, and used a simple and efficient Sonogashira cross-coupling reaction to construct the required functionalized precursor. With sclerotiorin as a control, the activities of the newly synthesized analogues were evaluated against seven fungal pathogens, and several promising candidates (compounds 3a₁, 3d₂, 3e₂, 3f₂ and 3k₂) with greater activity and simpler structures than sclerotiorin were discovered. In addition, preliminary structure-activity relationships were studied, which revealed that not only the chlorine or bromine substituent at the 5-position of the nucleus but also the phenyl group at the 3-position and the substituent pattern on it contributed crucially to the observed antifungal activity. Analogues with a methyl substituent at the 1-position have reduced levels of activity, while those with a free hydroxyl group in place of acetoxy at the quaternary center of the bicyclic ring system retain activity.

Experimental studies demonstrated that alcohols and amines can undergo a CF(3)COOAg-catalyzed nucleophilic addition at the outer C=N position of Ag(III) NCPs, leading to C-3-alkoxylated Ag(III) NCPs, which supports the computational result that the C=N bond on the periphery of Ag(III) NCPs is partially isolated from the 18 pi-electron macrocyclic conjugation system and is the active electrophilic center.

Echinopines A (1) and B (2), novel sesquiterpenoids with an unprecedented rearranged skeleton named echinopane, were isolated from the roots of Echinops spinosus. The structures were elucidated by extensive spectroscopic analysis. The relative configuration of 1 was assigned by a combination of NOESY correlations and a simulation analysis. A plausible biosynthetic pathway for echinopane was discussed.