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Starting from the structure of MDL 72222 and its analogs, the known 5-HT 3 receptor antagonists with verified nematicidal activity, we evaluated a diverse array of tropane derivatives that are characterized by the introduction of a variety of pentatomic heterocycles as bioisosteric replacements for the ester moiety of these 5-HT 3 receptor antagonists. The in vitro nematicidal activities of all the target compounds were tested against Bursaphelenchus xylophilus and Meloidogyne incognita. A preliminary structure-activity relationship (SAR) investigation demonstrated that the ester functionality in 5-HT 3 receptor antagonists could be replaced by a thiazole moiety (analog 5) with modest to good nematicidal activity. Specifically, compound 5bd exhibited excellent nematicidal activity against B. xylophilus with an LC 50/72 h of 7.80 mg/L, and 85% mortality at 40 mg/L against M. incognita. Furthermore, a stepwise structural modification of analog 5 led to the discovery of the structurally distinct compound 47b with advanced nematicidal activity, which had an LC 50/72 h of 5.96 mg/L against B. xylophilus. [Display omitted] • 72 novel tropane derivatives were synthesized containing variety of heterocycles. • Bioisosteric replacement and scaffold hopping were adopted in this study. • All the target compounds against B. xylophilus and M. incognita were evaluated. [ABSTRACT FROM AUTHOR]

The transmission of insect-borne viruses involves sophisticated interactions between viruses, host plants, and vectors. Chemical compounds play an important role in these interactions. Several studies reported that the plant virus tomato spotted wilt orthotospovirus (TSWV) increases host plant quality for its vector and benefits the vector thrips Frankliniella occidentalis. However, few studies have investigated the chemical ecology of thrips vectors, TSWV, and host plants. Here, we demonstrated that in TSWV-infected host plant Datura stramonium, (1) F. occidentalis were more attracted to feeding on TSWV-infected D. stramonium; (2) atropine and scopolamine, the main tropane alkaloids in D. stramonium, which are toxic to animals, were down-regulated by TSWV infection of the plant; and (3) F. occidentalis had better biological performance (prolonged adult longevity and increased fecundity, resulting in accelerated population growth) on TSWV-infected D. stramonium than on TSWV non-infected plants. These findings provide in-depth information about the physiological mechanisms responsible for the virus's benefits to its vector by virus infection of plant regulating alkaloid accumulation in the plant. [ABSTRACT FROM AUTHOR]

Purpose: Dopamine transporter (DAT) is a promising target for positron emission tomography (PET) imaging of many neuropsychiatric diseases. 18F-labelled N-alkyl tropane analogues were reported to be useful PET radioligands for DAT. However, the drawback of 18F-labelled tropane analogues is that N-alkyl on tropane is easily metabolized in vivo, which interferes with brain imaging. To develop a more in vivo stable DAT-targeted PET radioligand with high DAT affinity and specificity, in this study, we synthesized and compared a series of 18F-labelled novel deuterated N-fluoropropyl tropane derivatives [18F]4a-e for DAT tracing. Procedures: Five deuterated N-fluoropropyl-d6 tropane derivatives (4a-e) and corresponding non-deuterated compounds (6a-e) were synthesized, and their semi-inhibitory concentrations (IC50) were measured by competitive binding assay. The radioligands [18F]4a-e and [18F]6a-e were obtained by two-step one-pot radio-labelling reactions. The selectivity and specificity of these radioligands were evaluated by cellular uptake and microPET in normal rats. [18F]4e was selected for further investigation with microPET of the PD model, autoradiography and biodistribution experiments and compared with its non-deuterated [18F]6e. Finally, in vivo metabolic stability was analyzed by radio-HPLC. Results: Ten tropane compounds had high DAT affinity (IC50 = 2–21 nM), in which FP-CIT-d6 (4e) had the lowest IC50 value of 2.7 nM. Radiolabelled [18F]4a-e and [18F]6a-e were obtained with radiochemical yields ranging from 10.6 ± 2.8% to 35.1 ± 5.4% with molar activities >20 GBq/μmol and the radiochemical purities >99%. [18F]4e showed the highest cell uptake (12%) and CFT inhibition efficacy (∼72%) among [18F]4a-e. MicroPET results showed [18F]4e has the highest target to non-target ratio (striatum/cerebellum). Therefore, [18F]4e was then selected for further biological evaluation. Ex vivo autoradiography experiment confirmed high specific binding of [18F]4e towards DAT. Biodistribution results indicated that [18F]4e has a higher striatum/cerebellum value than [18F]FP-CIT ([18F]6e) at 30–120 min. Furthermore, in vivo metabolism studies in rats revealed improved stability of [18F]4e as compared with that of [18F]6e. Conclusions: The new probe [18F]4e is a promising candidate with good DAT affinity, specificity and metabolic stability for PET imaging, and might provide reliable diagnosis, treatment and prognostic detection of DAT-related neuropsychiatric diseases.

Tropane alkaloids (TAs) are heterocyclic nitrogenous metabolites found across seven orders of angiosperms, including Malpighiales (Erythroxylaceae) and Solanales (Solanaceae). Despite the well-established euphorigenic properties of Erythroxylaceae TAs like cocaine, their biosynthetic pathway remains incomplete. Using yeast as a screening platform, we identified and characterized the missing steps of TA biosynthesis in Erythroxylum coca. We first characterize putative E. coca polyamine synthase- and amine oxidase-like enzymes in vitro, in yeast, and in planta to show that the first tropane ring closure in Erythroxylaceae occurs via bifunctional spermidine synthase/N-methyltransferases and both flavin- and copper-dependent amine oxidases. We next identify a SABATH family methyltransferase responsible for the 2-carbomethoxy moiety characteristic of Erythroxylaceae TAs and demonstrate that its coexpression with methylecgonone reductase in yeast engineered to express the Solanaceae TA pathway enables the production of a hybrid TA with structural features of both lineages. Finally, we use clustering analysis of Erythroxylum transcriptome datasets to discover a cytochrome P450 of the CYP81A family responsible for the second tropane ring closure in Erythroxylaceae, and demonstrate the function of the core coca TA pathway in vivo via reconstruction and de novo biosynthesis of methylecgonine in yeast. Collectively, our results provide strong evidence that TA biosynthesis in Erythroxylaceae and Solanaceae is polyphyletic and that independent recruitment of unique biosynthetic mechanisms and enzyme classes occurred at nearly every step in the evolution of this pathway. [ABSTRACT FROM AUTHOR]

[Display omitted] • New derivatives of tropane scaffold were synthesized and examined for their cytotoxic effect. • The most active compounds 3, 4, 5, 9d and 14a displayed significant antitumor activities with IC 50 range of 9.50 – 30.15 μM. • Compound 3 was found to be the most potent Hsp90 inhibitor with IC 50 value of 56.58 ± 0.86 nM. • The Western blotting assay for the tested derivatives revealed a significant inhibition of Hsp90. • A molecular modeling study of the active derivatives was done where they have good binding affinities to Hsp90 via the key residues. New derivatives of tropane scaffold were prepared from the reaction of their thione or thioamide derivatives with α-halocarbonyl compounds. The structures of all new derivatives were assured and proved with their spectral data. The novel tropane derivatives were examined for their cytotoxicity on two colon tumor cell lines; Caco2 and HCT116 cells. The most active compounds 3 , 4 , 5 , 9d and 14a displayed significant antitumor activities with IC 50 range of 9.50 – 30.15 μM compared to doxorubicin. Moreover, they revealed reduced cytotoxic effect on WI‐38 normal ones, signifying their great safety. With the aim of better understanding the inhibitory potential of such compounds on heat-shock protein 90 (Hsp90), there activities were assessed against such enzyme demonstrating high inhibitory activities with IC 50 range of 56.58–78.85 nM. Western blotting was carried out to ensure the inhibitory activity on Hsp90, results showed that 3 markedly suppressed Hsp90 expression on Caco2 cell line. Additionally, a molecular docking analysis of the most potent derivatives at the Hsp90 binding site was carried out in order to approve the performed in vitro assays. [ABSTRACT FROM AUTHOR]

The transmission of insect-borne viruses involves sophisticated interactions between viruses, host plants, and vectors. Chemical compounds play an important role in these interactions. Several studies reported that the plant virus tomato spotted wilt orthotospovirus (TSWV) increases host plant quality for its vector and benefits the vector thrips Frankliniella occidentalis. However, few studies have investigated the chemical ecology of thrips vectors, TSWV, and host plants. Here, we demonstrated that in TSWV-infected host plant Datura stramonium, (1) F. occidentalis were more attracted to feeding on TSWV-infected D. stramonium; (2) atropine and scopolamine, the main tropane alkaloids in D. stramonium, which are toxic to animals, were down-regulated by TSWV infection of the plant; and (3) F. occidentalis had better biological performance (prolonged adult longevity and increased fecundity, resulting in accelerated population growth) on TSWV-infected D. stramonium than on TSWV non-infected plants. These findings provide in-depth information about the physiological mechanisms responsible for the virus’s benefits to its vector by virus infection of plant regulating alkaloid accumulation in the plant.

We present the development of novel ion‐selective electrodes for tropane, atropine, and scopolamine, as a general model for tropane alkaloids and drugs such as e. g. cocaine. These potentiometric sensors rely either on a metallocarborane or tetraphenylborate complex as recognition element and led to systems with a near‐Nernstian behaviour in the range of 10−5–10−2 mol/L and detection limits around 2 ⋅ 10−5 mol/L. Selectivity studies with commonly used drug additives (caffeine, phenacetin) and closely related tropane derivatives show very low influence of the additives and a structure dependent interference for the derivatives. Beside this, a hydrogel‐based concept with a similar performance was developed, which could be used for on‐site measurement of solid samples. The developed sensors therefore demonstrated their suitability and might be used to enable the development of portable sensor arrays for the quantification of a wide range of tropane alkaloids. [ABSTRACT FROM AUTHOR]

Background and Objective: Breast cancer is the most common form of cancer in women and is the leading cause of cancer-related deaths among women globally. In this study, we aimed to synthesize a series of tropane derivatives to investigate their Hsp90 inhibitory activity as well as their cytotoxic impact on breast cancer cells (MCF- 7 and MDA-MB-231)., Methods: Novel fused-tropane derivatives were created and produced as inhibitors of Hsp90, taking inspiration from XL888, a tropane medication used for treating cancer. The target compounds were screened in vitro to determine their ability to inhibit the activity of Hsp90., Results: All tropane derivatives displayed a good submicromolar inhibition of Hsp90 with IC50 values ranging from 52.64 to 76.05 nM, relative to XL888 reference medication (IC50 = 27.78 nM). Among all the compounds examined, tropane derivative 5 exhibited the highest level of Hsp90 inhibitory action, with an IC50 value of 52.64 nM. Furthermore, the cytotoxic activity of all compounds was evaluated against two breast cancer cell lines, namely MCF-7 and MDA-MB-231. Tropane derivative 5 exhibited greater potency than doxorubicin against both cell lines. In addition, it demonstrated a safety profile significantly superior to that of doxorubicin when tested on normal human cells (WI-38 cells), thereby confirming its exceptional level of safety. The western blotting analysis demonstrated a 2.4-fold reduction in Hsp90 expression in MCF-7 cells. Furthermore, the molecular docking analysis has provided additional evidence for the capacity of compound 5 to effectively bind with the target Hsp90 enzyme., Conclusion: We have succeeded in synthesizing novel tropane hybrids exhibiting significant anti-Hsp90 action, similar to XL888 analogues., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The Prilezhaev epoxidation of N -Boc-protected 3-cyclobutylidenetropane 1a affords a 1:2 mixture of compounds 2a and 2b , in which tropane and cyclobutane fragments are spiro-connected to the oxirane ring in endo - and exo -fashion, respectively. The exo -isomer 2b is obtained in 89% yield and 97% selectivity via the dioxirane oxidation of 1a. BF3-catalyzed isomerization of exo -oxirane 2b results in a 1:1 mixture of the spirocyclic ketones endo 3a and exo 3b containing spiro-connected tropane and cyclopentanone rings, while endo -epoxide 2a gives exclusively endo -ketone 3a. Prilezhaev and dioxirane epoxidations of N -Boc-protected 3-cyclopropylidenetropane 1b affords a mixture of endo - and exo -oxiranes 2c and 2d. Compounds 2c and 2d are not isolated in individual forms since they isomerize into a mixture of spirocyclic ketones endo 3c and exo 3d. Removal of the Boc groups from ketones 3a – d gives the corresponding hydrochlorides of aminoketones 4a – d in quantitative yields. Quantum chemical calculations predict that the rearrangement of endo -epoxides into the corresponding endo -ketones involving BF3-containing intermediates has by 4.4–7.9 kcal/mol lower activation barriers than the respective conversion of the exo -epoxides into exo -ketones. The cyclopropyl-containing dispiroepoxides 2c and 2d are predicted to interconvert faster into the corresponding ketones compared to their less strained cyclobutyl counterparts 2a and 2b. [ABSTRACT FROM AUTHOR]

In a recent study, Zeng et al. uncovered 3β-tigloyloxytropane synthase (TS) in Atropa belladonna, characterizing its mitochondrial localization and substrate specificity. The discovery of this enzyme opens up new bioengineering possibilities for tropane alkaloids (TAs), enhancing the potential for sustainable agriculture and expanding our knowledge of TA biosynthesis., Competing Interests: Declaration of interests The authors declare no conflicts of interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Die Synthese von Tropanen über eine mikrowellenunterstützte, stereoselektive 6π‐elektrocyclische Ringöffnung/ Huisgen‐[3+2]‐Cycloadditionskaskade von cyclopropanierten Pyrrol‐ und Furanderivaten mit elektronenarmen Dipolarophilen wird demonstriert. Ausgehend von Furanen oder Pyrrolen sind 8‐Aza‐ und 8‐Oxabicyclo[3.2.1]octane in zwei Schritten sowohl dia‐ als auch enantioselektiv zugänglich und stellen vielseitige Bausteine für die Synthese pharmazeutisch relevanter Zielmoleküle, insbesondere neuer Kokain‐Analoga mit verschiedenen Substituenten an den C‐6/C‐7‐Positionen des Tropanringsystems, dar. Darüber hinaus ist das 2‐Azabicyclo[2.2.2]octan‐Grundgerüst (Isochinuclidin), das in vielen natürlichen und pharmazeutischen Produkten vertreten ist, über diese Synthesestrategie zugänglich. [ABSTRACT FROM AUTHOR]

Conformationally restrained exo -isomers of N -Boc-protected spiro[2′,2′-difluorocyclopropane-3′,2′-tropanes] were synthesized in 62–83% yield via absolutely diastereoselective cycloaddition of CF2 , generated in situ from Me3 SiCF3 /NaI in refluxing THF, to double bonds of 3-alkylidenetropanes. Standard removal of Boc protecting groups afforded corresponding exo -spiro[2′,2′-difluorocyclopropane-3′,2′-tropane] hydrochlorides in 82–94% yields. DFT and CCSD(T) calculations revealed that the observed exo -selectivity of difluorocarbene addition is likely to be caused by a lower activation barrier of the exo -difluorocyclopropanation compared to the endo -reaction. [ABSTRACT FROM AUTHOR]

The present study describes the isolation of convolvine from the roots of the Tunisian plant Convolvulus dorycnium L. and its synthesis through a four-step sequence starting from tropine. Then, an efficient synthesis of N -(het)aryltropanes derivatives by a sequence of a palladium-catalyzed N-arylationof convolvine has been established. This strategy enabled access to unknown tropane scaffolds of biological interests. [ABSTRACT FROM AUTHOR]

The structure of a salt of diprotonated endo-3-aminotropane crystallized with a copper(II) anionic cluster is reported, viz. (C8H18N2)[CuCl3(NO3)(H2O)]. Neither ion in the salt has been structurally characterized previously. In the crystal, the ions pack together to form a three-dimensional structure held together by a network of intermolecular N—H...O, O—H...Cl and N—H...Cl hydrogen-bonding interactions. Selective crystallization of the title compound can be considered as a simple method for the separation of the exo and endo isomers of 3-aminotropane.

Introduction: Tropane-derived medications have historically played a substantial role in pharmacotherapy. Both natural and synthetic derivatives of tropane find application in addressing diverse medical conditions. Prominent examples of tropane-based drugs include hyoscine butylbromide, recognized for its antispasmodic properties, atropine, employed as a mydriatic, maraviroc, known for its antiviral effects. trospium chloride, utilized as a spasmolytic for overactive bladder, and ipratropium, a bronchodilator., Areas Covered: We compiled patents pertaining to the biological activity of substances containing tropane up to the year 2023 and categorized them according to the specific type of biological activity they exhibit. ScienceFinder, ScienceDirect, and Patent Guru were used to search for scientific articles and patent literature up to 2023., Expert Opinion: Pharmaceutical researchers in academic and industrial settings have shown considerable interest in tropane derivatives. Despite this, there remains a substantial amount of work to be undertaken. A focused approach is warranted for the exploration and advancement of both natural and synthetic bioactive molecules containing tropane, facilitated through collaborative efforts between academia and industry. Leveraging contemporary techniques and technologies in medicinal and synthetic chemistry, including high throughput screening, drug repurposing,and biotechnological engineering, holds the potential to unveil novel possibilities and accelerate the drug discovery process for innovative tropane-based pharmaceuticals.

The genus Datura (Solanaceae) contains nine species of medicinal plants that have held both curative utility and cultural significance throughout history. This genus’ particular bioactivity results from the enormous diversity of alkaloids it contains, making it a valuable study organism for many disciplines. Although Datura contains mostly tropane alkaloids (such as hyoscyamine and scopolamine), indole, beta-carboline, and pyrrolidine alkaloids have also been identified. The tools available to explore specialized metabolism in plants have undergone remarkable advances over the past couple of decades and provide renewed opportunities for discoveries of new compounds and the genetic basis for their biosynthesis. This review provides a comprehensive overview of studies on the alkaloids of Datura that focuses on three questions: How do we find and identify alkaloids? Where do alkaloids come from? What factors affect their presence and abundance? We also address pitfalls and relevant questions applicable to natural products and metabolomics researchers. With both careful perspectives and new advances in instrumentation, the pace of alkaloid discovery—from not just Datura—has the potential to accelerate dramatically in the near future.

Series of benzylidene and benzyl derivatives of 1,2,5-trimethyl-, 2,2,6,6-tetramethylpiperidyl-, and tropylamines were synthesized and screened for anti-ischemic activity in rats. The lead compound was identified as 2,2,6,6-tetramethyl-N-(3,4,5-trimethoxybenzyl)piperidin-4-amine, the anti-ischemic activity of which was statistically significantly greater than that of the reference drug trimetazidine in a myocardial subendocardial ischemia model. [ABSTRACT FROM AUTHOR]

Objective · To provide theoretical guidance for the design of molecules with high activity by building the quantitative structure-activity relationship (QSAR) model for tropane compounds as muscarinic M3 receptor antagonists. Methods · Six compounds (J1-J6) were prepared with3α-hydroxy-tropane (J0) as the starting material by modifying the structure in C-3α position of the tropane skeleton. The antagonistic activity of new tropane compounds to muscarinic M3 receptors on tracheal rings of guinea pigs was evaluated by functional assays in vitro. The antagonistic parameters (pA2) of new tropane compounds prepared in this paper and former studies were applied to construct the QSAR model. The information about structural optimization was acquired by analyzing the effect of steric field and electrostatic field of model on activity of tropane compounds. Results · The six new tropane compounds showed obvious antagonistic activity against M3 receptors. Among them, J4 had the greatest activity (pA2=7.992) . The cross-validation correlation coefficient squared (q2) and the non-cross-validated correlation coefficient squared (r2) of the QSAR model were 0.585 and 0.993, respectively.Conclusion · The antagonistic activity to muscarinic M3 receptors can be obviously improved, when the conjugating extent of π-bonds is large and O or N atoms participate in conjugation on the rings in the R-substituting group at C-3α position of the compounds. [ABSTRACT FROM AUTHOR]

Abstract Herein, development of a reliable and specific fluorometric assay was disclosed for the sensitive detection of atropine. The method was designed using the surface molecularly imprinted polymer on high fluorescent graphene quantum dots (GQDs). Molecularly imprinted polymer capped GQDs (MIP-GQDs) were prepared through the common co -polymerization reaction of 3-(3-aminopropyl) triethoxysilane (APTES) and tetraethyl orthosilicate (TEOS), act as the main functional and cross-linking monomers, respectively. The used template for this reaction was atropine. The created blue luminescent MIP-GQDs composite, which had a great affinity to adsorb atropine from the sample solution, could lead to a notable fluorescence quenching. In fact, GQDs act as the recognizing antenna for adsorbed atropine into the specific MIP sites. The linear association between the observed quenching effect and atropine concentration was exploited to design a selective assay to the detection of atropine. After optimization process, a linear calibration graph was achieved in the atropine concentration range of 0.5–300 ng mL−1 with a detection limit of 0.22 ng mL−1. Exploitation of high specific MIP technique along with high fluorescent GQDs provided a highly selective and sensitive assay for atropine as a model analyte. It was adequately utilized for the analysis of atropine in biological samples. Graphical Abstract Specific fluorometric assay for atropine based on the surface molecularly imprinted high fluorescent graphene quantum dots (MIP-GQDs). Unlabelled Image Highlights • Synthesis of molecularly imprinted polymer capped graphene quantum dots (MIP-GQDs). • High fluorescence emission of MIP-GQDs dependent to the excitation wavelength. • Great affinity of luminescent MIP-GQDs toward the atropine molecules. • Fluorescence quenching effect of atropine proportional to its concentration. • Specific and sensitive determination of atropine in plasma. [ABSTRACT FROM AUTHOR]

Dopamine transporter (DAT) is a promising target for positron emission tomography (PET) imaging of many neuropsychiatric diseases. 18F-labelled N-alkyl tropane analogues were reported to be useful PET radioligands for DAT. However, the drawback of 18F-labelled tropane analogues is that N -alkyl on tropane is easily metabolized in vivo , which interferes with brain imaging. To develop a more in vivo stable DAT-targeted PET radioligand with high DAT affinity and specificity, in this study, we synthesized and compared a series of 18F-labelled novel deuterated N-fluoropropyl tropane derivatives [18F] 4a-e for DAT tracing. Five deuterated N-fluoropropyl-d 6 tropane derivatives (4a-e) and corresponding non-deuterated compounds (6a-e) were synthesized, and their semi-inhibitory concentrations (IC 50) were measured by competitive binding assay. The radioligands [18F] 4a-e and [18F] 6a-e were obtained by two-step one-pot radio-labelling reactions. The selectivity and specificity of these radioligands were evaluated by cellular uptake and microPET in normal rats. [18F] 4e was selected for further investigation with microPET of the PD model, autoradiography and biodistribution experiments and compared with its non-deuterated [18F] 6e. Finally, in vivo metabolic stability was analyzed by radio-HPLC. Ten tropane compounds had high DAT affinity (IC 50 = 2–21 nM), in which FP-CIT-d 6 (4e) had the lowest IC 50 value of 2.7 nM. Radiolabelled [18F] 4a-e and [18F] 6a-e were obtained with radiochemical yields ranging from 10.6 ± 2.8% to 35.1 ± 5.4% with molar activities >20 GBq/μmol and the radiochemical purities >99%. [18F] 4e showed the highest cell uptake (12%) and CFT inhibition efficacy (∼72%) among [18F] 4a-e. MicroPET results showed [18F] 4e has the highest target to non-target ratio (striatum/cerebellum). Therefore, [18F] 4e was then selected for further biological evaluation. Ex vivo autoradiography experiment confirmed high specific binding of [18F] 4e towards DAT. Biodistribution results indicated that [18F] 4e has a higher striatum/cerebellum value than [18F]FP-CIT ([18F] 6e) at 30–120 min. Furthermore, in vivo metabolism studies in rats revealed improved stability of [18F] 4e as compared with that of [18F] 6e. The new probe [18F] 4e is a promising candidate with good DAT affinity, specificity and metabolic stability for PET imaging, and might provide reliable diagnosis, treatment and prognostic detection of DAT-related neuropsychiatric diseases. [ABSTRACT FROM AUTHOR]

Spirotropanyl oxindole alkaloids like alstonisine and chitosenine show a wide range of bioactivites. We report the first enantioselective synthesis of the spirotropanyl oxindole scaffold by means of a bimetallic relay catalysis strategy. A new class of E‐oximino α‐diazo ketones was developed for the intramolecular generation of transient azomethine ylides catalyzed by an achiral RhII complex and a subsequent intermolecular 1,3‐dipolar cycloaddition catalyzed by a chiral N,N′‐dioxide NdIII Lewis acid complex. The enantioselectively catalyzed transformation has broad scope and yields the desired spirotropanyl oxindole cycloadducts in high yields and with very high enantio‐ and diastereoselectivity. Ring, ring: The first enantioselectively catalyzed synthesis of the spirotropanyl oxindole scaffold, which is characteristic of bioactive alkaloids like alstonisine and chitosenine, was developed. The method involves a bimetallic relay catalysis strategy, with a highly enantioselective 1,3‐dipolar cycloaddition as the key step. [ABSTRACT FROM AUTHOR]

We recently reported a convergent strategy to access the polycyclic guanidinium alkaloid (+)-batzelladine B via an aldol addition–retro-aldol–aza-Michael addition cascade. Here we describe the application of this approach toward the total syntheses of (+)-batzelladine E, (−)-dehydrobatzelladine C, and (+)-batzelladine K. The identification of suitable methods to functionalize a common tropane core by electrophilic alkynylation and nucleophilic 1,2-addition were essential to generalizing this approach. We provide evidence for the intermediacy of an acylallene species in the cascade reaction. [ABSTRACT FROM AUTHOR]

The spread of Datura sp. in European countries influences crop management and implies continuous food safety issues because of tropane alkaloids, atropine and scopolamine, the most relevant natural toxic compounds of this weed. These alkaloids can contaminate cereals to such a level that hampers food/feed related use and diverts batches of contaminated raw materials towards ultimate disposal such as burning. As no unambiguous information has been available on the fate of tropane alkaloids in soils, our study focused on the quantification and follow-up of these toxic residues in a soil experiment where the tropane alkaloids were mixed to the soil in the form of naturally contaminated unhulled millet in 1:40 millet:soil ratio – this approach provides a more realistic scenario compared to standard solution based spiking. To achieve accurate results, soil and millet extraction processes have been validated and a liquid chromatography – mass spectrometry set-up was addressed to provide selective and quantitative analysis. The initial concentration of atropine (75 ng g − 1 ) and scopolamine (47 ng g − 1 ) in the soil decreased with > 90% in 15 days and reached a high level of elimination (> 97%) in 29 days. This observation opens an option for the use of tropane contaminated millet or millet waste other than burning, as these toxic alkaloids can be significantly degraded in the soil system. On the other hand, the persistence of intact tropane alkaloids in soils might be questioned to the extent that calls the attention to the (re)assignment of their supposed allelopathic effects. [ABSTRACT FROM AUTHOR]

The genus Erythroxylum contains species used by indigenous people of South America long before the domestication of plants. Two species, E. coca and E. novogranatense, have been utilized for thousands of years specifically for their tropane alkaloid content. While abuse of the narcotic cocaine has impacted society on many levels, these species and their wild relatives contain untapped resources for the benefit of mankind in the form of foods, pharmaceuticals, phytotherapeutic products, and other high-value plant-derived metabolites. In this review, we describe the current state of knowledge of members within the genus and the recent advances in the realm of molecular biology and biochemistry.

Background: different Solanaceae and Erythroxylaceae species produce tropane alkaloids. These alkaloids are the starting material in the production of different pharmaceuticals. The commercial demand for tropane alkaloids is covered by extracting them from cultivated plants. Datura stramonium is cultivated under greenhouse conditions as a source of tropane alkaloids. Here we investigate the effect of different levels of water availability in the soil on the production of tropane alkaloids by D. stramonium. Methods: We tested four irrigation levels on the accumulation of tropane alkaloids. We analyzed the profile of tropane alkaloids using an untargeted liquid chromatography/mass spectrometry method. Results: Using a combination of informatics and manual interpretation of mass spectra, we generated several structure hypotheses for signals in D. stramonium extracts that we assign as putative tropane alkaloids. Quantitation of mass spectrometry signals for our structure hypotheses across different anatomical organs allowed us to identify patterns of tropane alkaloids associated with different levels of irrigation. Furthermore, we identified anatomic partitioning of tropane alkaloid isomers with pharmaceutical applications. Conclusions: Our results show that soil water availability is an effective method for maximizing the production of specific tropane alkaloids for industrial applications.