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Toh-seok Kam - One of the best experts on this subject based on the ideXlab platform.
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A Hexacyclic, Iboga-Derived Monoterpenoid Indole with a Contracted Tetrahydroazepine C-Ring and Incorporation of an Isoxazolidine Moiety, a Seco-Corynanthean, an Aspidosperma-Aspidosperma Bisindole with Anticancer Properties, and the Absolute Configu
Journal of natural products, 2016Co-Authors: Choy-eng Nge, Noel F. Thomas, Siew-huah Lim, Yun-yee Low, Kae Shin Sim, Toh-seok KamAbstract:Examination of the EtOH extract of the Malayan Tabernaemontana corymbosa resulted in the isolation of three new alkaloids, viz., cononuridine (1), an unusual hexacyclic, Iboga-derived, monoterpenoid indole characterized by contraction of the tetrahydroazepine C-ring and incorporation of an additional isoxazolidine ring, taberisidine (2), a seco-corynanthean alkaloid, and conofolidine (3), an Aspidosperma-Aspidosperma bisindole that showed pronounced in vitro growth inhibitory activity against an array of human cancer cell lines, including KB, vincristine-resistant KB, PC-3, LNCaP, MCF7, MDA-MB-231, HT-29, and HCT 116 cells. The structures and absolute configurations of 1 and 3 and the absolute configuration of the novel pyridopyrimidine indole alkaloid vernavosine (4) were confirmed by X-ray diffraction analysis. A reasonable biosynthesis route to cononuridine starting from an Iboga precursor is presented.
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Ibogan, Aspidosperman, Vincamine, and Bisindole Alkaloids from a Malayan Tabernaemontana corymbosa: Iboga Alkaloids with C-20α Substitution
Journal of natural products, 2016Co-Authors: Choy-eng Nge, Kam-weng Chong, Noel F. Thomas, Siew-huah Lim, Yun-yee Low, Toh-seok KamAbstract:Ten new indole alkaloids (1-10) comprising five Ibogan, two aspidosperman, one vincamine, and two bisindole alkaloids, in addition to 32 known alkaloids, were isolated from the stem-bark extract of a Malayan Tabernaemontana corymbosa. The structures of these alkaloids were determined based on analysis of the NMR and MS data and, in five instances (1, 3, 5, 6, 8), confirmed by X-ray diffraction analysis. Two of the Iboga alkaloids, conodusines B (2) and C (3), and the Iboga-containing bisindole tabernamidine B (10) are notable for the presence of an α-substituted acetyl group at C-20 of the Iboga carbon skeleton. The Iboga alkaloid (+)-conodusine E (5) had MS and NMR data that were identical to those of (-)-ervatamine I, recently isolated from Ervatamia hainanensis. Establishment of the absolute configuration of (+)-conodusine E (5) was based on analysis of the ECD data, correlation with (-)-heyneanine, and X-ray analysis, which showed that (+)-5 belongs to the same enantiomeric series as exemplified by (-)-coronaridine. The configuration at C-20' of the previously reported Tabernaemontana bisindole alkaloid 19'-oxotabernamine (renamed tabernamidine B) required revision based on the present results. Several of the bisindoles showed pronounced in vitro growth inhibitory activity against drug-sensitive and vincristine-resistant KB cells.
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Ibogan, Aspidosperman, Vincamine, and Bisindole Alkaloids from a Malayan Tabernaemontana corymbosa: Iboga Alkaloids with C‑20α Substitution
2016Co-Authors: Choy-eng Nge, Kam-weng Chong, Noel F. Thomas, Siew-huah Lim, Yun-yee Low, Toh-seok KamAbstract:Ten new indole alkaloids (1–10) comprising five Ibogan, two aspidosperman, one vincamine, and two bisindole alkaloids, in addition to 32 known alkaloids, were isolated from the stem-bark extract of a Malayan Tabernaemontana corymbosa. The structures of these alkaloids were determined based on analysis of the NMR and MS data and, in five instances (1, 3, 5, 6, 8), confirmed by X-ray diffraction analysis. Two of the Iboga alkaloids, conodusines B (2) and C (3), and the Iboga-containing bisindole tabernamidine B (10) are notable for the presence of an α-substituted acetyl group at C-20 of the Iboga carbon skeleton. The Iboga alkaloid (+)-conodusine E (5) had MS and NMR data that were identical to those of (−)-ervatamine I, recently isolated from Ervatamia hainanensis. Establishment of the absolute configuration of (+)-conodusine E (5) was based on analysis of the ECD data, correlation with (−)-heyneanine, and X-ray analysis, which showed that (+)-5 belongs to the same enantiomeric series as exemplified by (−)-coronaridine. The configuration at C-20′ of the previously reported Tabernaemontana bisindole alkaloid 19′-oxotabernamine (renamed tabernamidine B) required revision based on the present results. Several of the bisindoles showed pronounced in vitro growth inhibitory activity against drug-sensitive and vincristine-resistant KB cells
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A Hexacyclic, Iboga-Derived Monoterpenoid Indole with a Contracted Tetrahydroazepine C‑Ring and Incorporation of an Isoxazolidine Moiety, a Seco-Corynanthean, an Aspidosperma-Aspidosperma Bisindole with Anticancer Properties, and the Absolute Configu
2016Co-Authors: Choy-eng Nge, Noel F. Thomas, Siew-huah Lim, Yun-yee Low, Kae Shin Sim, Toh-seok KamAbstract:Examination of the EtOH extract of the Malayan Tabernaemontana corymbosa resulted in the isolation of three new alkaloids, viz., cononuridine (1), an unusual hexacyclic, Iboga-derived, monoterpenoid indole characterized by contraction of the tetrahydroazepine C-ring and incorporation of an additional isoxazolidine ring, taberisidine (2), a seco-corynanthean alkaloid, and conofolidine (3), an Aspidosperma-Aspidosperma bisindole that showed pronounced in vitro growth inhibitory activity against an array of human cancer cell lines, including KB, vincristine-resistant KB, PC-3, LNCaP, MCF7, MDA-MB-231, HT-29, and HCT 116 cells. The structures and absolute configurations of 1 and 3 and the absolute configuration of the novel pyridopyrimidine indole alkaloid vernavosine (4) were confirmed by X-ray diffraction analysis. A reasonable biosynthesis route to cononuridine starting from an Iboga precursor is presented
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Ibogan, Tacaman, and Cytotoxic Bisindole Alkaloids from Tabernaemontana. Cononusine, an Iboga Alkaloid with Unusual Incorporation of a Pyrrolidone Moiety
Journal of natural products, 2015Co-Authors: Kuan-hon Lim, Siew-huah Lim, Yun-yee Low, Vijay J. Raja, Tracey D. Bradshaw, Toh-seok KamAbstract:Six new indole alkaloids, viz., cononusine (1, a rare example of an Iboga−pyrrolidone conjugate), ervaluteine (2), vincamajicine (3), tacamonidine (4), 6-oxoIbogaine (5), and N 4 -chloromethylnorfluorocurarine chloride (6), and two new vobasinyl-Iboga bisindole alkaloids, ervatensines A (7) and B (8), in addition to other known alkaloids, were isolated from the stem-bark extract of the Malayan Tabernaemontana corymbosa. The structures of these alkaloids were established on the basis of NMR and MS analyses and, in one instance (7), confirmed by X-ray diffraction analysis. Vincamajicine (3) showed appreciable activity in reversing multidrug resistance in vincristine-resistant KB cells (IC50 2.62 μM), while ervatensines A (7) and B (8) and two other known bisindoles displayed pronounced in vitro growth inhibitory activity against human KB cells (IC50
Surajit Sinha - One of the best experts on this subject based on the ideXlab platform.
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Synthesis of Iboga-like isoquinuclidines: Dual opioid receptors agonists having antinociceptive properties.
Bioorganic & medicinal chemistry, 2014Co-Authors: Tuhin Suvro Banerjee, Surajit Sinha, Sibasish Paul, Sumantra DasAbstract:Some novel Iboga-analogues consisting of benzofuran moiety and dehydroisoquinuclidine ring connected by -CH2-, (CH2)2 and (CH2)3 linkers have been synthesized with the view to develop potential antinociceptive drugs. The compounds 14 and 21 showed binding at the μ-opioid receptor (MOR), while the compound 11a exhibited dual affinities at both MOR and κ-opioid receptor (KOR). MAP kinase activation indicated all three compounds have opioid agonistic properties. The presence of a double bond and endo-methylcarboxylate group in the dehydroisoquinuclidine ring and the benzofuran and methylene spacer appeared to be essential for opioid receptor binding. Further studies demonstrated 11a caused significant antinociception in mice in the hot-plate test which was comparable to that produced by morphine. The compound 11a was also found to be nontremorigenic unlike various Iboga congeners. This study identifies a new pharmacophore which may lead to the development of suitable substitute of morphine in the treatment of pain.
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total synthesis of Ibogaine epiIbogaine and their analogues
Tetrahedron, 2012Co-Authors: Goutam Kumar Jana, Surajit SinhaAbstract:Efficient total synthesis of Ibogaine, epiIbogaine and their analogues has been described. An intramolecular reductive-Heck type cyclization was used for the construction of seven-membered indoloazepine ring to access Iboga-skeleton. Larock’s heteroannulation reaction was employed for the creation of suitably substituted indole and Diels–Alder reaction was employed for the construction of the isoquinuclidine ring present in Iboga alkaloids.
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Reductive Heck coupling: an efficient approach toward the Iboga alkaloids. Synthesis of Ibogamine, epiIbogamine and Iboga analogs
Tetrahedron Letters, 2012Co-Authors: Goutam Kumar Jana, Surajit SinhaAbstract:Abstract A mild and efficient synthetic route to the Iboga scaffold by employing reductive-Heck type annulation is described. The utility of this process is demonstrated by the direct access to the Ibogamine, epiIbogamine and Iboga-analogs. The cyclization precursors were readily obtained from 2-iodoaniline by heteroannulation reaction with suitable alkynes followed by iodination.
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Synthesis of new series of Iboga analogues
Tetrahedron Letters, 2011Co-Authors: Sibasish Paul, Sankha Pattanayak, Surajit SinhaAbstract:Synthesis of new Iboga-analogues, replacing the indole ring with a benzofuran moiety has been described. Starting materials are the suitably substituted benzofuran derivatives and have been synthesized by Pd-catalyzed reactions. The conversion of endo-6-methylcarboxylate substituted dehydroisoquinuclidine to exo-isomer, a key component of Iboga-alkaloids has been achieved in the presence of NaOMe in methanol under reflux conditions.
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Synthesis of Iboga alkaloids by Pd-catalyzed heteroannulation of 2-iodoaniline with an internal alkyne as the key step
Tetrahedron Letters, 2010Co-Authors: Goutam Kumar Jana, Surajit SinhaAbstract:Abstract A convenient synthetic route to the Iboga-scaffolds is described. Important steps include a Pd-catalyzed regiospecific indole formation between internal alkyne-substituted isoquinuclidine and 2-iodoaniline. The final cyclization was done using Trost’s Pd(II)–Ag(I) mixed-metal-mediated cyclization method originally developed for the synthesis of Ibogamine. Both exo - (Iboga) and endo -isomers (epi-Iboga) at C-19 substitution with –CO 2 Me have been reported.
Kooi-mow Sim - One of the best experts on this subject based on the ideXlab platform.
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Conodirinines A and B, Novel Vobasine‐Iboga Bisindoles Incorporating an Additional Tetrahydro‐1,3‐oxazine Unit on the Vobasinyl Moiety
Helvetica Chimica Acta, 2003Co-Authors: Toh-seok Kam, Kooi-mow SimAbstract:Two novel bisindole alkaloids of the vobasine-Iboga type, viz., conodirinines A and B, in which the vobasinyl unit has incorporated an additional tetrahydrooxazine ring, were obtained from the leaf extract of the Malayan species Tabernaemontana corymbosa, and their structures were established by spectroscopic analysis.
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conodirinines a and b novel vobasine Iboga bisindoles incorporating an additional tetrahydro 1 3 oxazine unit on the vobasinyl moiety
Helvetica Chimica Acta, 2003Co-Authors: Toh-seok Kam, Kooi-mow SimAbstract:Two novel bisindole alkaloids of the vobasine-Iboga type, viz., conodirinines A and B, in which the vobasinyl unit has incorporated an additional tetrahydrooxazine ring, were obtained from the leaf extract of the Malayan species Tabernaemontana corymbosa, and their structures were established by spectroscopic analysis.
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Five new Iboga alkaloids from Tabernaemontana corymbosa.
Journal of natural products, 2002Co-Authors: Toh-seok Kam, Kooi-mow SimAbstract:Five new indole alkaloids of the Ibogan type (1-5), in addition to 12 other known Iboga alkaloids, were obtained from the leaf and stem-bark extract of the Malayan species Tabernaemontana corymbosa, viz., 19(S)-hydroxyIbogamine (1), 19-epi-isovoacristine (2), isovoacryptine (3), 3R/S-ethoxyheyneanine (4), and 3R/S-ethoxy-19-epi-heyneanine (5). The structures were determined using NMR and MS analysis and comparison with known related compounds.
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conodiparines a d new bisindoles from tabernaemontana reversal of vincristine resistance with cultured cells
Bioorganic & Medicinal Chemistry Letters, 1998Co-Authors: Toh-seok Kam, Kooi-mow Sim, Takashi Koyano, Mitsuhide Toyoshima, Masahiko Hayashi, Kanki KomiyamaAbstract:Abstract Four new bisindoles of the vobasine-Iboga type, conodiparines A-D were obtained from Tabernaemontana corymbosa which showed appreciable activity in reversing resistance in vincristine-resistant KB cells.
Ricardo Reyes-chilpa - One of the best experts on this subject based on the ideXlab platform.
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Strategies for the in vitro production of antiaddictive Ibogan type alkaloids from Apocynaceae species
Plant Cell Tissue and Organ Culture (PCTOC), 2019Co-Authors: Felix Krengel, Josefina Herrera-santoyo, Teresa De Jesús Olivera-flores, Ricardo Reyes-chilpaAbstract:Monoterpenoid indole alkaloids (MIAs) of the Ibogan type, such as Ibogaine, have shown promising antiaddictive effects against several drugs of abuse in humans and animal models of addiction. Unfortunately, international Ibogaine demand has led to the overexploitation of natural populations of the African species Tabernanthe Iboga (Apocynaceae), the main source of this alkaloid. Therefore, it is necessary to identify alternative Ibogan type alkaloid-containing plant species, as well as to develop new sustainable production systems for said group of pharmaceutically important compounds. In this review, we focus on strategies for the in vitro production of the antiaddictive Ibogan type MIAs coronaridine, Ibogamine, voacangine, and Ibogaine (collectively named “CIVI-complex”) from Apocynaceae species, with particular emphasis on the Tabernaemontana genus. Since plant tissue culture (PTC)-related information on the CIVI-complex is scarce, we also consider reports on the in vitro production of other Ibogan type MIAs and where necessary, of compounds belonging to the aspidospermatan, corynanthean, and plumeran type. This review aims at giving an overview of potential strategies to produce antiaddictive Ibogan type alkaloids from in vitro cultures of Apocynaceae species.
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Extraction and Conversion Studies of the Antiaddictive Alkaloids Coronaridine, Ibogamine, Voacangine, and Ibogaine from Two Mexican Tabernaemontana Species (Apocynaceae)
Chemistry & Biodiversity, 2019Co-Authors: Felix Krengel, Marco V. Mijangos, Marisol Reyes-lezama, Ricardo Reyes-chilpaAbstract:: Several species from the Apocynaceae family, such as Tabernanthe Iboga, Voacanga africana, and many Tabernaemontana species, produce Ibogan type alkaloids, some of which present antiaddictive properties. In this study, we used gas chromatography/mass spectrometry (GC/MS) to examine the efficiency of methanol, acetone, ethyl acetate, dichloromethane, chloroform, and hydrochloric acid in extracting the antiaddictive compounds coronaridine, Ibogamine, voacangine, and Ibogaine (altogether the CIVI-complex) from the root barks of Tabernaemontana alba and Tabernaemontana arborea. These Mexican species have recently shown great potential as alternative natural sources of the aforementioned substances. Methanol proved to be the most suitable solvent. Furthermore, the crude methanolic extracts could be engaged in a one-step demethoxycarbonylation process that converted coronaridine and voacangine directly into its non-carboxylic counterparts Ibogamine and Ibogaine, respectively, without the intermediacy of their carboxylic acids. The established protocol straightforwardly simplifies the alkaloid mixture from four to two majority compounds. In summary, our findings facilitate and improve both the qualitative and quantitative analysis of CIVI-complex-containing plant material, as well as outlining a viable method for the bulk production of these scientifically and pharmaceutically important substances from Mexican Tabernaemontana species.
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Strategies for the in vitro production of antiaddictive Ibogan type alkaloids from Apocynaceae species
Plant Cell Tissue and Organ Culture, 2019Co-Authors: Felix Krengel, Teresa De Jesús Olivera-flores, Josefina Herrera-santoyo, Ricardo Reyes-chilpaAbstract:Monoterpenoid indole alkaloids (MIAs) of the Ibogan type, such as Ibogaine, have shown promising antiaddictive effects against several drugs of abuse in humans and animal models of addiction. Unfortunately, international Ibogaine demand has led to the overexploitation of natural populations of the African species Tabernanthe Iboga (Apocynaceae), the main source of this alkaloid. Therefore, it is necessary to identify alternative Ibogan type alkaloid-containing plant species, as well as to develop new sustainable production systems for said group of pharmaceutically important compounds. In this review, we focus on strategies for the in vitro production of the antiaddictive Ibogan type MIAs coronaridine, Ibogamine, voacangine, and Ibogaine (collectively named “CIVI-complex”) from Apocynaceae species, with particular emphasis on the Tabernaemontana genus. Since plant tissue culture (PTC)-related information on the CIVI-complex is scarce, we also consider reports on the in vitro production of other Ibogan type MIAs and where necessary, of compounds belonging to the aspidospermatan, corynanthean, and plumeran type.
Xiao-qi Zhang - One of the best experts on this subject based on the ideXlab platform.
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ervaoffines e g three Iboga type alkaloids featuring ring c cleavage and rearrangement from ervatamia officinalis
RSC Advances, 2017Co-Authors: Zhi-wen Liu, Ben-qin Tang, Wen-jing Wang, Xiao-jun Huang, Lei Shi, Qinghua Zhang, Jian Zhang, Xiao-qi ZhangAbstract:Ervaoffine E (1), a new pseudoindoxyl alkaloid possessing a unique rearranged 1,4-diazacycloheptane skeleton, ervaoffine F (2), the first 5,6-seco-6-nor Iboga-type alkaloid featuring ring C cleavage, and ervaoffine G (3), bearing an unusual contracted valerolactam ring, together with six known alkaloids were isolated from Ervatamia officinalis. Their structures and absolute configurations were determined by extensive spectroscopic analysis, single-crystal X-ray diffraction and quantum chemical ECD calculations. Plausible biogenetic pathways of these new alkaloids were also proposed and provided new insights into the structural plasticity of ring C in Iboga-type alkaloids. Compound 3 exhibited a significant neuroprotective effect against oxygen-glucose deprivation (OGD)-induced damage of cultured cortical neurons, an in vitro model of ischemic stroke.
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Ervaoffines E–G, three Iboga-type alkaloids featuring ring C cleavage and rearrangement from Ervatamia officinalis
RSC Advances, 2017Co-Authors: Zhi-wen Liu, Ben-qin Tang, Wen-jing Wang, Xiao-jun Huang, Lei Shi, Qinghua Zhang, Jian Zhang, Xiao-qi ZhangAbstract:Three novel alkaloids (1–3) reveal the high structural plasticity of ring C in Iboga-type alkaloids.
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New Iboga-type alkaloids from Ervatamia hainanensis
RSC Advances, 2016Co-Authors: Zhi-wen Liu, Xiao-jun Huang, Ren-wang Jiang, Lei Shi, Jian Zhang, Han-lin Xiao, Guo Liu, Xiao-qi ZhangAbstract:Seven new Iboga-type alkaloids (1–7) and six known ones (8–13) were obtained from Ervatamia hainanensis. Their structures with absolute configurations were determined by spectroscopic data, Mosher's method, single crystal X-ray diffraction and electric circular dichroism (ECD) analyses. The relationship between the absolute configuration of C-7 in Iboga-type 7-hydroxyindolenine alkaloids and the Cotton effects in the ECD spectrum was established for the first time. The neural activities of these compounds were evaluated, and compound 11 exhibited protective effects against MPP+ (1-methyl-4-phenylpyridinium)-induced damage in primary cortical neurons.
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Iboga-Type Alkaloids from Ervatamia officinalis
Journal of natural products, 2014Co-Authors: Ben-qin Tang, Wen-jing Wang, Xiao-jun Huang, Lei Wang, Ren-wang Jiang, Ting-ting Yang, Lei Shi, Xiao-qi ZhangAbstract:Seven new Iboga-type alkaloids, ervaoffines A-D (1-4), (7S)-3-oxoIbogaine hydroxyindolenine (5), Ibogaine-5,6-dione (6), and 19-epi-5-oxovoacristine (7), and 10 known alkaloids were isolated from Ervatamia officinalis. The absolute configurations of 1-7 were determined through X-ray diffraction and electronic circular dichroism (ECD) analyses. Ervaoffines A and B represent the first Iboga-type pseudoindoxyl alkaloids in which the C-2 spiro carbon configuration is opposite to that of other members of this class, such as iboluteine (8). The relationship between the absolute configuration of the spiro carbons and the Cotton effect in the ECD spectrum is established for the first time for Iboga-type pseudoindoxyl and oxindole alkaloids. Additionally, a plausible biogenetic pathway for these alkaloids is proposed.
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Iboga-Type Alkaloids from Ervatamia officinalis
2014Co-Authors: Ben-qin Tang, Wen-jing Wang, Xiao-jun Huang, Lei Wang, Ren-wang Jiang, Ting-ting Yang, Lei Shi, Xiao-qi ZhangAbstract:Seven new Iboga-type alkaloids, ervaoffines A–D (1–4), (7S)-3-oxoIbogaine hydroxyindolenine (5), Ibogaine-5,6-dione (6), and 19-epi-5-oxovoacristine (7), and 10 known alkaloids were isolated from Ervatamia officinalis. The absolute configurations of 1–7 were determined through X-ray diffraction and electronic circular dichroism (ECD) analyses. Ervaoffines A and B represent the first Iboga-type pseudoindoxyl alkaloids in which the C-2 spiro carbon configuration is opposite to that of other members of this class, such as iboluteine (8). The relationship between the absolute configuration of the spiro carbons and the Cotton effect in the ECD spectrum is established for the first time for Iboga-type pseudoindoxyl and oxindole alkaloids. Additionally, a plausible biogenetic pathway for these alkaloids is proposed
