Chemistry Of Alkaloids Research Articles

Recent Progress in the Isolation and Bioactivities of Carbazole Alkaloids

Objective/Background Carbazole derivatives have a tricyclic skeleton, consisting of a central pyrrole ring fused with two benzene rings. Carbazole derivatives are an important class of nitrogen-containing heterocyclic compounds that are widely found in nature and in synthetic source. These heterocycles possess a wide range of bioactivities and some of them have been marketed as drugs for the treatment of various diseases. Although some review articles on carbazole alkaloids have appreared in the literature, they are quite outdated. The current study offers a comprehensive review on the isolation and bioactivities of carbazole alkaloids within a decade. The article might be useful for chemists who work in alkaloid chemistry as well as pharmaceutical area. Methods ‘Carbazole alkaloids’ was the most useful keyword to search for literature data. References have been collected from various resources such as Google Scholar, SciFinder, and PubMed. More than 70 electronic publications were obtained from these resources. Results More than 230 carbazole alkaloids have been isolated and structurally elucidated from different sources. Carbazole alkaloids possess a wide range of bioactivities, such as antimicrobial, antiimflamatory, anticancer, neuroprotective properties activities. Conclusion In this review article, we have summarized 66 studies on isolation and bioactivities of carbazole alkaloids in the literature. More than 230 carbazole alkaloid compounds have been isolated and identified. In addition, the article also gives an overview on bioactivities of carbazole alkaloids.

Stereodivergent Total Synthesis of Tacaman Alkaloids.

This paper describes a concise, asymmetric and stereodivergent total synthesis of tacaman alkaloids. A key step in this synthesis is the biocatalytic Baeyer-Villiger oxidation of cyclohexanone, which was developed to produce seven-membered lactones and establish the required stereochemistry at the C14 position (92 % yield, 99 % ee, 500 mg scale). Cis- and trans-tetracyclic indoloquinolizidine scaffolds were rapidly synthesized through an acid-triggered, tunable acyl-Pictet-Spengler type cyclization cascade, serving as the pivotal reaction for building the alkaloid skeleton. Computational results revealed that hydrogen bonding was crucial in stabilizing intermediates and inducing different addition reactions during the acyl-Pictet-Spengler cyclization cascade. By strategically using these two reactions and the late-stage diversification of the functionalized indoloquinolizidine core, the asymmetric total syntheses of eight tacaman alkaloids were achieved. This study may potentially advance research related to the medicinal chemistry of tacaman alkaloids.

Stereodivergent Total Synthesis of Tacaman Alkaloids

Abstract: This paper describes a concise, asymmetric and stereodivergent total synthesis of tacaman alkaloids. A key step in this synthesis is the biocatalytic Baeyer‐Villiger oxidation of cyclohexanone, which was developed to produce seven‐membered lactones and establish the required stereochemistry at the C14 position (92% yield, 99% ee, 500 mg scale). Cis‐ and trans‐tetracyclic indoloquinolizidine scaffolds were rapidly synthesized through an acid‐triggered, tunable acyl‐Pictet‐Spengler type cyclization cascade, serving as the pivotal reaction for building the alkaloid skeleton. Computational results revealed that hydrogen bonding was crucial in stabilizing intermediates and inducing different addition reactions during the acyl‐Pictet‐Spengler cyclization cascade. By strategically using these two reactions and the late‐stage diversification of the functionalized indoloquinolizidine core, the asymmetric total syntheses of eight tacaman alkaloids were achieved. This study may potentially advance research related to the medicinal chemistry of tacaman alkaloids.

Isolation and Bioactivities of Stemona Alkaloid: A Review

Objective/Background: In Chinese, Vietnamese, and Thai traditional medicine of Southeast Asian countries, Stemonaceae plants have long been employed. Various studies have proved that these herbal plants contain Stemona alkaloids with valuable medicinal value. Although some review articles on Stemona alkaloids have appeared in the literature, they are quite outdated. The current study offers a comprehensive review of the isolation and bioactivities of Stemona alkaloids. The article might be useful for chemists who work in alkaloid chemistry as well as pharmaceutical areas. Methods: “ Stemona alkaloids” was the most useful keyword to search for literature data. References have been collected from various resources such as Google Scholar, SciFinder, and PubMed. More than 120 electronic publications were obtained from these resources. Results: More than 250 Stemona alkaloids from 8 groups have been isolated and structurally elucidated from Stemonaceae plants. Extracts from these plants as well as isolated compounds possess a wide range of bioactivities, such as antituberculosis, antibacterial, antifungal, and antihelmintic properties activities. Conclusion: In this review article, we have summarized 116 studies on the isolation and bioactivities of Stemona alkaloids in the literature. More than 250 Stemona alkaloid compounds have been isolated and identified. In addition, the article also gives an overview of the bioactivities of Stemona alkaloids.

Overview of the chemistry and biological activities of natural atisine-type diterpenoid alkaloids.

Atisine-type C20-diterpenoid alkaloids (DAs) are a very important class of diterpenoid alkaloids, which play an important role in the biosynthesis of DAs. To date, 87 atisine-type DAs and 11 bis-DAs containing an atisine unit have been reported from five genera in two families. The genus Spiraea in Rosaceae family could be regarded as the richest resource for atisine-type DAs, followed by the genera Delphinium and Aconitum in the Ranunculaceae family. Among the reported atisine-type DAs, several possess unprecedented skeletons. Natural atisine-type DAs have a wide range of biological activities, including antitumor, antiplatelet aggregation, biological control, and anti-inflammatory, analgesic, antiarrhythmic, and cholinesterase inhibitory effects, which are closely related to their structures. In particular, the antiparasitic effect of atisine-type DAs is more prominent than that of other types of DAs, which highlights their potential in antiparasite drug discovery. In summary, the high chemical and biological diversity of atisine-type DAs indicates their great potential as a vast resource for drug discovery.

Greening up organic reactions with caffeine: applications, recent developments, and future directions.

Numerous studies in the field of alkaloid chemistry have provided researchers with valuable insights into their unique properties as catalysts. Among the diverse natural catalysts, caffeine has emerged as a green, expedient, and biodegradable catalyst with high efficiency and applicability. Interest in using caffeine as a catalyst has burgeoned over the past few years with its role in diverse multicomponent reactions. Preparation of its imidazolium salts and further conversion to Nitrogen Heterocyclic Carbene (NHC) ligands and ionic liquids offers new paradigms. Caffeine has also played a multifaceted role as a support material in influencing the structural properties of nanoparticles. We hope that the chemistry of caffeine and its applications for sustainable organic transformations discussed in this review will stimulate new thinking and open new avenues in this field.

Nature-Inspired Chemistry of Complex Alkaloids: Combining Targeted Molecular Networking Approach and Semisynthetic Strategy to Access Rare Communesins in a Marine-Derived Penicillium expansum.

Communesins are rare alkaloids isolated from fungi of the genus Penicillium. In this work, the extract of a marine-derived Penicillium expansum strain was studied using targeted molecular networking approach allowing to detect 65 communesins including 55 new ones. A fragmentation pattern for dimethylvinyl communesins was established and a script was implemented allowing to predict the structure and map all communesins in a global molecular network. A semisynthetic strategy was carried out to obtain some minor congeners from the two isolated communesins A and B. Nine communesins were then synthetised: two of them were already described as produced by the studied strain; four are new natural products which occurrence in the extracts was confirmed; three are new semi-synthetic analogues never described so far. These communesins were evaluated for their cytotoxicity on two human cancer cell lines KB and MCF-7 leading to a preliminary study of their structure-activity relationships.

Chemistry and biology of ent-morphinan alkaloids.

Morphinan alkaloids have attracted constant attention since the isolation of morphine by Sertürner in 1805. However, a group of 45 compounds possessing a complete ent-morphinan backbone can also be found in the literature. These compounds are related to the morphinandienone subgroup and display a substitution pattern which is different from the morphinans. In particular, these alkaloids could be substituted at position C-2 and C-8 either by a hydroxy function or a methoxy moiety. Four groups of ent-morphinan alkaloids can be proposed, the salutaridine, pallidine, cephasugine and erromangine series. Interestingly, the botanical distribution of the ent-morphinans is more widespread than for the morphinans and includes the Annonaceae, Berberidaceae, Euphorbiaceae, Fumariaceae, Hernandiaceae, Lauraceae, Menispermaceae, Monimiaceae, Papaveraceae, and Ranunculaceae families. To date, their exact mode of production remains elusive and their interplay with the biosynthetic pathway of other classes of benzyltetrahydroisoquinoline alkaloids, in particular aporphines, should be confirmed. Exploration of the biological and therapeutic potential of these compounds is limited to some areas, namely central nervous system (CNS), inflammation, cancer, malaria and viruses. Further studies should be conducted to identify the cellular/molecular targets in view of promoting these compounds as new scaffolds in medicinal chemistry.

Chemistry, bioactivity, biosynthesis, and total synthesis of stemmadenine alkaloids.

Covering: up to July 2022Stemmadenine alkaloids are a restrictive sub-group of monoterpene indole alkaloids, represented by two congeners: stemmadenine and vallesamine. Their skeleton is defined by the cleavage of the C-3-C-7 bond of the Strychnos group's pentacyclic scaffold in monoterpene indole alkaloids. The parent alkaloid stemmadenine acts as a key intermediate in the biosynthesis of several major monoterpene indole alkaloid families, including regular Strychnos alkaloids, Aspidosperma alkaloids, and Iboga alkaloids. In this review, a complete coverage of the stemmadenine alkaloids, from the early reports till the present day at 2022, are presented, and their diverse biological activities are briefly described. Moreover, the biosynthetic proposal for stemmadenine and the proposed biogenetic conversion of stemmadenine-type alkaloids into vallesamine-type congeners are discussed in detail. Moreover, the successful synthetic strategies to access the strained stemmadenine scaffolds are fully reviewed.

Plant growth and phytoactive alkaloid synthesis in kratom [Mitragyna speciosa (Korth.)] in response to varying radiance.

Leaves harvested from kratom [Mitragyna speciosa (Korth.)] have a history of use as a traditional ethnobotanical medicine to combat fatigue and improve work productivity in Southeast Asia. In recent years, increased interest in the application and use of kratom has emerged globally, including North America, for its potential application as an alternative source of medicine for pain management and opioid withdrawal syndrome mitigation. Although the chemistry and pharmacology of major kratom alkaloids, mitragynine and 7-hydroxymitragynine, are well documented, foundational information on the impact of plant production environment on growth and kratom alkaloids synthesis is unavailable. To directly address this need, kratom plant growth, leaf chlorophyll content, and alkaloid concentration were evaluated under three lighting conditions: field full sun (FLD-Sun), greenhouse unshaded (GH-Unshaded), and greenhouse shaded (GH-Shaded). Nine kratom alkaloids were quantified using an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Greenhouse cultivation generally promoted kratom height and width extension by 93–114% and 53–57%, respectively, compared to FLD-Sun. Similarly, total leaf area and leaf number were increased by 118–160% and 54–80% under such conditions. Average leaf size of plants grown under GH-Shaded was 41 and 69% greater than GH-Unshaded and FLD-Sun, respectively; however, no differences were observed between GH-Unshaded and FLD-Sun treatments. At the termination of the study, total leaf chlorophyll a+b content of FLD-Sun was 17–23% less than those grown in the greenhouse. Total leaf dry mass was maximized when cultivated in the greenhouse and was 89–91% greater than in the field. Leaf content of four alkaloids to include speciociliatine, mitraphylline, corynantheidine, and isocorynantheidine were not significantly impacted by lighting conditions, whereas 7-hydroxymitragynine was below the lower limit of quantification across all treatments. However, mitragynine, paynantheine, and corynoxine concentration per leaf dry mass were increased by 40%, 35%, and 111%, respectively, when cultivated under GH-Shaded compared to FLD-Sun. Additionally, total alkaloid yield per plant was maximized and nearly tripled for several alkaloids when plants were cultivated under such conditions. Furthermore, rapid, non-destructive chlorophyll evaluation correlated well (r2 = 0.68) with extracted chlorophyll concentrations. Given these findings, production efforts where low-light conditions can be implemented are likely to maximize plant biomass and total leaf alkaloid production.

The Use of Cinchona Alkaloid Derivatives as Chiral Ligands and Organocatalysts in Asymmetric Catalysis

: Cinchona alkaloids are natural products extracted from cinchona plants, which contain quinine, quinidine, cinchonine, and cinchonidine. During the past 30 years, due to their attractive structural properties, these compounds have been used as chiral skeletons and organocatalysts in asymmetric organic synthesis. In this review, we summarize the applications of cinchona alkaloids derivatives in asymmetric catalysis recently developed by our group, including oxidation, reduction, and C-C bonds formation. These studies have solved some of the problems with the various asymmetric reactions discussed, while also enriching alkaloids chemistry, providing new ideas for the design and synthesis of chiral catalysts, and providing abundant experimental data for the chiral induction process.

Occurrence and Chemistry of Tropane Alkaloids in Foods, with a Focus on Sample Analysis Methods: A Review on Recent Trends and Technological Advances.

Tropane alkaloids (TAs) are natural toxins produced by different plants, mainly from the Solanaceae family. The interest in TAs analysis is due to the serious cases of poisoning that are produced due to the presence of TA-producing plants in a variety of foods. For this reason, in recent years, different analytical methods have been reported for their control. However, the complexity of the matrices makes the sample preparation a critical step for this task. Therefore, this review has focused on (a) collecting the available data in relation to the occurrence of TAs in foods for human consumption and (b) providing the state of the art in food sample preparation (from 2015 to today). Regarding the different food categories, cereals and related products and teas and herbal teas have been the most analyzed. Solid–liquid extraction is still the technique most widely used for sample preparation, although other extraction and purification techniques such as solid-phase extraction or QuEChERS procedure, based on the use of sorbents for extract or clean-up step, are being applied since they allow cleaner extracts. On the other hand, new materials (molecularly imprinted polymers, mesostructured silica-based materials, metal–organic frameworks) are emerging as sorbents to develop effective extraction and purification methods that allow lower limits and matrix effects, being a future trend for the analysis of TAs.

Transcription Factors in Alkaloid Engineering.

Plants produce a large variety of low-molecular-weight and specialized secondary compounds. Among them, nitrogen-containing alkaloids are the most biologically active and are often used in the pharmaceutical industry. Although alkaloid chemistry has been intensively investigated, characterization of alkaloid biosynthesis, including biosynthetic enzyme genes and their regulation, especially the transcription factors involved, has been relatively delayed, since only a limited number of plant species produce these specific types of alkaloids in a tissue/cell-specific or developmental-specific manner. Recent advances in molecular biology technologies, such as RNA sequencing, co-expression analysis of transcripts and metabolites, and functional characterization of genes using recombinant technology and cutting-edge technology for metabolite identification, have enabled a more detailed characterization of alkaloid pathways. Thus, transcriptional regulation of alkaloid biosynthesis by transcription factors, such as basic helix–loop–helix (bHLH), APETALA2/ethylene-responsive factor (AP2/ERF), and WRKY, is well elucidated. In addition, jasmonate signaling, an important cue in alkaloid biosynthesis, and its cascade, interaction of transcription factors, and post-transcriptional regulation are also characterized and show cell/tissue-specific or developmental regulation. Furthermore, current sequencing technology provides more information on the genome structure of alkaloid-producing plants with large and complex genomes, for genome-wide characterization. Based on the latest information, we discuss the application of transcription factors in alkaloid engineering.

Alkaloids and Selected Topics in Their Thermochemistry.

Alkaloid chemistry is varied and complex. Many alkaloids attract a great deal of interest because of their physiological activity, yet surprisingly little is known about the thermochemistry of these compounds, especially in the gas phase. In this paper, we investigate the thermochemical characteristics, specifically demethoxylation enthalpies rather than those derived from trans-methoxylation reactions, of a series of biologically relevant alkaloids in their condensed phase.

Chemistry and synthesis of major opium alkaloids: a comprehensive review

Chemistry and synthesis of major opium alkaloids: a comprehensive review

Alkaloids as Potential Phytochemicals against SARS-CoV-2: Approaches to the Associated Pivotal Mechanisms.

Since its inception, the coronavirus disease 2019 (COVID-19) pandemic has infected millions of people around the world. Therefore, it is necessary to find effective treatments against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), as it is the viral source of COVID-19. Alkaloids are one of the most widespread plant-derived natural compounds with prominent antiviral effects. Accordingly, these phytochemicals have been promising candidates towards discovering effective treatments for COVID-19. Alkaloids have shown potential anti-SARS-CoV activities via inhibiting pathogenesis-associated targets of the Coronaviridae family that are required for the virus life cycle. In the current study, the chemistry, plant sources, and antiviral effects of alkaloids, as well as their anti-SARS-CoV-2 effect with related mechanisms, are reviewed towards discovering an effective treatment against COVID-19.

Comprehensive Overview on the Chemistry and Biological Activities of Selected Alkaloid Producing Marine-Derived Fungi as a Valuable Reservoir of Drug Entities.

Marine-associated fungal strains act as a valuable reservoir of bioactive diverse secondary metabolites including alkaloids which are highly popular by their biological activities. This review highlighted the chemistry and biology of alkaloids isolated from twenty-six fungal genera associated with marine organisms and marine sea sediments. The selected fungi are from different marine sources without focusing on mangroves. The studied fungal genera comprises Acrostalagmus, Arthrinium, Chaetomium, Cladosporium, Coniothyrium, Curvularia, Dichotomomyces, Eurotium, Eutypella, Exophiala, Fusarium, Hypocrea, Microsphaeropsis, Microsporum, Neosartorya, Nigrospora, Paecilomyces, Penicillium, Pleosporales, Pseudallescheria, Scedosporium, Scopulariopsis, Stagonosporopsis, Thielavia, Westerdykella, and Xylariaceae. Around 347 alkaloid metabolites were isolated and identified via chromatographic and spectroscopic techniques comprising 1D and 2D NMR (one and two dimensional nuclear magnetic resonance) which were further confirmed using HR-MS (high resolution mass spectrometry) and Mosher reactions for additional ascertaining of the stereochemistry. About 150 alkaloids showed considerable effect with respect to the tested activities. Most of the reported bioactive alkaloids showed considerable biological activities mainly cytotoxic followed by antibacterial, antifungal, antiviral, antioxidant; however, a few showed anti-inflammatory and antifouling activities. However, the rest of the compounds showed weak or no activity toward the tested biological activities and required further investigations for additional biological activities. Thus, alkaloids isolated from marine-associated fungi can afford an endless source of new drug entities that could serve as leads for drug discovery combating many human ailments.

Exploring the Chemistry of Alkaloids from Malaysian Mitragyna speciosa (Kratom) and the Role of Oxindoles on Human Opioid Receptors.

Ten indole and oxindole alkaloids (1-10) were isolated from the freshly collected leaves of Malaysian Mitragyna speciosa (Kratom). The chemical structures of these compounds were established on the basis of extensive 1D and 2D NMR and HRMS data analysis. The spectroscopic data of mitragynine oxindole B (4) are reported herein for the first time. The spatial configuration of mitragynine oxindole B (4) was confirmed by single-crystal X-ray diffraction. Simultaneous quantification of the isolated alkaloids in the M. speciosa leaf specimens collected from different locations in the northern region of Peninsular Malaysia was also performed using UPLC-MS/MS. The oxindole alkaloids (1-4) and the indole alkaloid (10) were assessed for binding affinity at opioid receptors. Corynoxine (1) showed high binding affinity to μ-opioid receptors with a Ki value of 16.4 nM. Further, corynoxine (1) was 1.8-fold more potent than morphine in rats subjected to a nociceptive hot plate assay. These findings have important implications for evaluating the combined effects of the minor oxindole alkaloids in the overall therapeutic activity of M. speciosa.

The iboga enigma: the chemistry and neuropharmacology of iboga alkaloids and related analogs.

Covering: 2000 up to 2020 Few classes of natural products have inspired as many chemists and biologists as have the iboga alkaloids. This family of monoterpenoid indole alkaloids includes the anti-addictive compound ibogaine as well as catharanthine, a precursor to the chemotherapeutic vinblastine. Despite being known for over 120 years, these small molecules continue to challenge our assumptions about biosynthetic pathways, catalyze our creativity for constructing complex architectures, and embolden new approaches for treating mental illness. This review will cover recent advances in both the biosynthesis and chemical synthesis of iboga alkaloids as well as their use as next-generation neurotherapeutics. Whenever appropriate, we provide historical context for the discoveries of the past decade and indicate areas that have yet to be resolved. While significant progress regarding their chemistry and pharmacology has been made since the 1960s, it is clear that the iboga alkaloids will continue to stoke scientific innovation for years to come.

Chemistry and biological activities of hetisine-type diterpenoid alkaloids.

Hetisine-type C20-diterpenoid alkaloids (DAs) are one of the most important DA subtypes. During the past decades, a total of 157 hetisine-type DAs were obtained from plants from seven genera in three families, most of which were isolated from the genera Aconitum and Delphinium in the Ranunculaceae family. Structurally, hetisine-type DAs are characterized by a heptacyclic hetisane skeleton formed by the linkage of C(14)–C(20) and N–C(6) bonds in an atisine-type DA, and their structural diversity is created by the states of the N atom and various substituents. Pharmacological studies have revealed a wide range of pharmacological actions for hetisine-type DAs, including antiarrhythmic, antitumor, antimicrobial and insecticidal activities, as well as effects on peripheral vasculature, which are closely related to their chemical structures. In particular, the prominent antiarrhythmic effects and low toxicity of hetisine-type DAs highlight their potential in antiarrhythmic drug discovery. Hetisine-type DAs with diverse bioactivities are promising lead structures for further development as commercial agents in medicine.