Research Update:Stemona root.

  seminal trace...Stemona Root Extract.10:1.Bai Bu Stemona Root Radix Stemonae.Stemona sessilifolia(Miq.)Franch.et Sav.Zhi Li Bai Bu,Stemona japonica Bl. Miq.,Wan Sheng Bai Bu,Stemona tuberosa Lour,Dui Ye Bai Bu,Radix Stemonae Sessilifoliae,Radix Stemonae,Radix Stemonae Tuberosae...

 


   Phytochemical info of Stemona root.

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 Definition:Stemona root are majorly composed of
 Chemical information disclosed as following table:


   Research Update:Stemona root.Stemona sessilifolia,Stemona japonica,Stemona tuberosa.

  Alkaloids from Stems and Leaves of Stemona japonica and Their Insecticidal Activities.:J Nat Prod. 2007 Dec 29;Tang CP, Chen T, Velten R, Jeschke P, Ebbinghaus-Kintscher U, Geibel S, Ye Y.yye@mail.shcnc.ac.cn.

 Five new alkaloids, 6beta-hydroxystemofoline ( 1), 16-hydroxystemofoline ( 2), neostemofoline ( 3), protostemodiol ( 4), and 13-demethoxy-11( S*),12( R*)-dihydroprotostemonine ( 5), along with 10 known alkaloids, were isolated from stems and leaves of Stemona japonica. Their structures were elucidated by 1D and 2D NMR and other spectroscopic studies. The insecticidal activity of the agonist 16-hydroxystemofoline ( 2) and antagonist 13-demethoxy-11( S*),12( R*)-dihydroprotostemonine ( 5) was demonstrated by electrophysiological in vitro tests on the insect nicotinic acetylcholine receptor and by in vivo screenings against relevant agricultural insect pests.

  Antibacterial stilbenoids from the roots of Stemona tuberosa.:Phytochemistry. 2008 Jan;69(2):457-63. Epub 2007 Sep 10.Lin LG, Yang XZ, Tang CP, Ke CQ, Zhang JB, Ye Y.State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu-Chong-Zhi Road, Zhangjiang Hi-tech Park, Shanghai 201203, PR China.

 Twelve dihydrostilbenes, stilbostemins N-Y (1-12), and a phenanthraquinone, stemanthraquinone (13), were isolated and identified from roots of Stemona tuberosa, along with five known dihydrostilbenes. Their structures were established on the basis of 1D and 2D NMR and other spectroscopic analyses. Dihydrostilbene 8 exhibited strong activity against Bacillus pumilus (MIT 12.5-25mug/mL). Many tested compounds exhibited moderate antibacterial activities.

  Antibacterial constituents from Stemona sessilifolia.:J Asian Nat Prod Res. 2007 Apr-Aug;9(3-5):479-85.Zhang T, Zhang YZ, Tao JS.College of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cai-Lun Road, Shanghai 201203, China.

 Bioassay-guided fractionation led to the isolation of eight compounds from Stemona sessilifolia. Of the eight isolates, three new bibenzyls, stilbostemins M-O (1-3), and a new tocopherol, 6-methoxy-3,4-dehydro-delta-tocopherol (4) were revealed together with four known compounds 3,5-dihydroxy-2'-methoxy bibenzyl (5), 3,5-dihydroxy bibenzyl (6), beta-tocopherol (7), and gamma-tocopherol (8). Compounds 5, 6, and 8 exhibited strong antibacterial activities against Staphylococcus aureus and S. epidermidis.

  Alkaloids from the roots of Stemona saxorum.:J Nat Prod. 2007 Aug;70(8):1356-9. Epub 2007 Jul 18.Wang YZ, Tang CP, Dien PH, Ye Y.State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu-Chong-Zhi Road, Zhangjiang Hi-tech Park, Shanghai 201203, People's Republic of China.

 Five new Stemona alkaloids, cochinchistemoninone (1), stemokerrin-N-oxide (2), oxystemokerrilactone (3), saxorumamide (4a), and isosaxorumamide (4b), as well as 12 known compounds, were isolated from the roots of Vietnamese Stemona saxorum. The structures of these alkaloids were characterized on the basis of spectroscopic methods.

  Quality evaluation of Radix Stemonae through simultaneous quantification of bioactive alkaloids by high-performance liquid chromatography coupled with diode array and evaporative light scattering detectors.:Biomed Chromatogr. 2007 Oct;21(10):1088-94.Li SL, Jiang RW, Hon PM, Cheng L, Xu HX, Greger H, But PP, Shaw PC.Institute of Chinese Medicine, Department of Biology and Department of Biochemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, People's Republic of China.

 A high-performance liquid chromatography coupled with diode array detection and evaporative light scattering detection (HPLC-DAD-ELSD) method was developed to simultaneously quantify six major bioactive alkaloids belonging to different structure types in Radix Stemonae, Bai-Bu in Chinese, a traditionally used antitussive and insecticidal medicinal material in China and other countries of Southeast Asia. Diode array detector (DAD) with the wavelengths at 307 and 260 nm was used to monitor the conjugated system of protostemonine (2) and maistemonine (4), respectively, whereas evaporative light scattering detector (ELSD) was employed to detect croomine (1), stemoninine (3), neotuberostemonine (5) and tuberostemonine (6), the other four analytes with no or poor chromophores. The assay was validated to be sensitive, precise and accurate, with a detection limit of 3.64-0.04 microg/mL depending on the individual analytes. The overall intra- and inter-day variations were less than 9.3%, and the overall recoveries higher than 91.2%, respectively. The correlation coefficients of the calibration curves were better than 0.996 for all analytes. The newly established method was successfully utilized to determine six major components in the genuine sources of Radix Stemonae: Stemona japonica, S. sessilifolia and S. tuberosa. Significant variations of contents of these components were demonstrated in samples of these three species. This simple, rapid, low-cost and reliable method is suitable for the routine quality control of herbal medicines containing bioactive components with different structure types such as Radix Stemonae.


  Stilbenoids from Stemona sessilifolia.:J Asian Nat Prod Res. 2007 Apr-Aug;9(3-5):261-6.Yang XZ, Tang CP, Ke CQ, Ye Y.State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica/SIBS, Chinese Academy of Sciences, 355 Zu-Chong-Zhi Road, Zhangjiang Hightech Park, 201203 Shanghai, China.

 Two new dihydrostilbenes, stilbostemins H (1), I (2), and a new dihydrophenanthrene, stemanthrene E (3), were isolated and identified from the roots of Stemona sessilifolia, together with known stilbostemins B, D and G, and stemanthrenes A and C (4-8). Structures of new stilbenoids were established by 1D and 2D (1)H NMR and (13)C NMR spectroscopic analyses.

  Isolation of chlorogenic acids and their derivatives from Stemona japonica by preparative HPLC and evaluation of their anti-AIV (H5N1) activity in vitro.:Phytochem Anal. 2007 May-Jun;18(3):213-8.Ge F, Ke C, Tang W, Yang X, Tang C, Qin G, Xu R, Li T, Chen X, Zuo J, Ye Y.State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu-Chong-Zhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, People's Republic of China.

 Two chlorogenic acids and five chlorogenic acid derivatives were simultaneously separated and purified from Stemona japonica by preparative high-performance liquid chromatography. Five of the collected compounds were over 95% pure while the other two compounds were over 90% pure. Their structures were elucidated as 3-O-feruloylquinic acid (1), 4-O-feruloylquinic acid (2), methyl 3-O-feruloylquinate (3), methyl 5-O-caffeyolquinate (4), methyl 4-O-feruloylquinate (5), ethyl 3-O-feruloylquinate (6) and the new compound ethyl 4-O-feruloylquinate (7) by UV, NMR and ESI-MS. All compounds were obtained from Stemona species for the first time, however compounds 6 and 7 are believed to be artefacts from the ethanol extraction. The anti-AIV (H5N1) activities were evaluated by Neutral Red uptake assay. Compounds 3 and 4 exerted moderate inhibitory effect against AIV (H5N1) in vitro.

  An approach to the synthesis of stenine.:Org Lett. 2007 Jun 7;9(12):2269-71. Epub 2007 May 10.Zhu L, Lauchli R, Loo M, Shea KJ.Department of Chemistry, Natural Sciences 1102, University of California Irvine, Irvine, California 92697, USA.

 A type 2 N-acylnitroso intramolecular Diels-Alder reaction followed by reductive N-O bond cleavage formed the B and C rings of the Stemona alkaloid stenine. Further elaboration provided the functionalized tricyclic core.

  Isolation and identification of an endophytic strain EJS-3 producing novel fibrinolytic enzymes.:Curr Microbiol. 2007 Jun;54(6):435-9. Epub 2007 May 8.Lu F, Sun L, Lu Z, Bie X, Fang Y, Liu S.College of Food Science and Technology, Nanjing Agricultural University, 210095, Nanjing, People's Republic of China.

 An endophytic strain EJS-3, which produces a novel fibrinolytic enzyme, was screened from root tissue of Stemona japonica (Blume) Miq, a chinese traditional medicine. This strain was identified as Paenibacillus polymyxa (DQ120522) by morphological, physiological, and biochemical tests and 16S rRNA gene sequence analysis. Two serine-type fibrinolytic enzymes with a relative molecular weight about 118 and 49 kDa, respectively, which are larger than known fibrinolytic enzymes, were found by the SDS-fibrin zymogram or by fibrin-inhibitor zymography gels. No work on P. polymyxa-producing fibrinolytic enzymes has been reported.

  Effect of Stemona curtisii root extract on P-glycoprotein and MRP-1 function in multidrug-resistant cancer cells.:Phytomedicine. 2007 Jun;14(6):381-9. Epub 2007 Apr 30. Limtrakul P, Siwanon S, Yodkeeree S, Duangrat C.Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. plimtrak@mail.med.cmu.ac.th

 Multidrug resistance (MDR) is the result of overexpression of membrane bound proteins that efflux chemotherapeutic drugs from the cells. Two proteins, P-glycoprotein (P-gp) and multidrug-resistance associated protein-1 (MRP-1) efflux chemotherapeutic agents out of the cancer cell that decrease intracellular drug accumulation, thereby decreasing the effectiveness of many chemotherapeutic agents. In the present study, the ethanolic extract of the roots of Stemona curtisii Hook. was tested for the potential ability to modulate the MDR phenotype and function of P-gp and MRP-1. The S. curtisii extract reversed the resistance to putative chemotherapeutic agents, including vinblastine, paclitaxel and colchicine of KB-V1 cells (MDR human cervical carcinoma with high P-gp expression) in a dose-dependent manner, but not in KB-3-1 cells (drug sensitive human cervical carcinoma, which lack P-gp expression). The root extract also increased the intracellular uptake and retention of (3)[H]-vinblastine in KB-V1 cells dose dependently. The extract did not influence MDR phenotype-mediated MRP-1 in MRP1-HEK293 (human embryonic kidney cells stably transfected with pcDNA3.1-MRP1-H10 which show high MRP-1 expression) and pcDNA3.1-HEK293 (wild type). In summary, the S. curtisii root extract modulated P-gp activity but not MRP-1 activity. The result obtained from this study strongly indicated that S. curtisii extract may play an important role as a P-gp modulator as used in vitro and may be effective in the treatment of multidrug-resistant cancers. The purified form of the active components of S. curtisii extract should be investigated in more details in order to explain the molecular mechanisms involved in P-gp modulation. This is the first report of new biological activity in this plant, which could be a potential source of a new chemosensitizer.


  Pyrrolo- and pyridoazepine alkaloids as chemical markers in Stemona species.:Phytochemistry. 2007 May;68(10):1417-27. Epub 2007 Apr 20.Schinnerl J, Brem B, But PP, Vajrodaya S, Hofer O, Greger H.Comparative and Ecological Phytochemistry Section, Faculty Center of Botany, University of Vienna, Rennweg 14, A-1030 Wien, Austria.

 Broad-based phytochemical investigations on 31 Stemona species and geographical provenances led to an overview concerning characteristic accumulation trends and the distribution of different Stemona alkaloids. Two major metabolic differences suggested a taxonomic segregation of the complex Stemona tuberosa group from the other species, and was supported by morphological characters. Whereas most of the Stemona species were characterised by protostemonine type alkaloids, the S. tuberosa group clearly deviated by accumulation trends towards tuberostemonine or croomine derived alkaloids belonging to two different skeletal types. Also of chemotaxonomic relevance was the structural divergence of protostemonine type alkaloids into pyrrolo- or pyridoazepine derivatives represented by stemofoline or oxystemokerrine, respectively, as major constituents. Their common occurrence in different provenances of S. curtisii, also deviating from the other species by various chromosome numbers, deserves special taxonomic attention. Species specific chemical markers were given by the unique accumulation of didehydrostemofoline (=asparagamine A) in S. collinsae and stemokerrine in S. kerrii. In contrast to previous reports, no bisdehydro derivatives with an aromatic pyrrole ring were detected supporting the hypothesis that these alkaloids are artifacts. A new stereoisomer of tuberostemonine was isolated and identified by spectroscopic methods.

  Total synthesis of the putative structure of stemonidine: the definitive proof of misassignment.:Org Lett. 2007 Apr 26;9(9):1769-72. Epub 2007 Mar 31.S¨¢nchez-Izquierdo F, Blanco P, Busqu¨¦ F, Alib¨¦s R, de March P, Figueredo M, Font J, Parella T.Universitat Autonoma de Barcelona, Departament de Qu¨ªmica, 08193 Bellaterra, Spain.

 The total synthesis of the putative structure of the Stemona alkaloid stemonidine has been completed. The key transformations include a 1,3-dipolar cycloaddition of a chiral nitrone derived from (S)-prolinol and a spirolactonization process involving the generation of the critical stereocenter. The NMR data of the synthetic material do not match those reported for the natural product. It is concluded that the structure assigned to stemonidine is incorrect, and it must be reassigned as stemospironine.

  Novel alkaloids from the roots of Stemona sessilifolia.:Chem Biodivers. 2007 Mar;4(3):523-30.Wang P, Liu AL, An Z, Li ZH, Du GH, Qin HL.Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College (Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education), Beijing 100050, PR China.

 Four new Stemona alkaloids, sessilistemonamines A-C (1-3, resp.) and dihydrostemoninine (4), were isolated from the roots of Stemona sessilifolia. Their structures and relative configurations were elucidated by means of in-depth 1D- and 2D-NMR-spectroscopic as well as mass-spectrometric experiments; and the structure of 4 was solved by X-ray single-crystal diffraction. The stereoisomeric compounds 1-3 share an unprecedented tetracyclic decahydro-1H-furo[2',3':4,5]cyclopenta[1,2-b]pyrrolo[1,2-a]azepine nucleus. Compounds 1 and 2 were found to be moderately active in terms of acetylcholinesterase (AchE) inhibition, with IC50 values of 68.8+/-9.5 and 17.1+/-2.5 microM, resp.

  Anti-mite activities of 25 kinds of traditional Chinese medicines for Demodex folliculorum.:Zhong Yao Cai. 2006 Oct;29(10):1013-5. Chinese.Tian Y, Li CP. School of Medicine, Anhui University of Science and Technology, Huainan 232001, China. yetian001@126.com

 OBJECTIVE: To explore traditional Chinese medicines (TCMs) with anti-mite activities for Dernodex folliculorum in vitro. METHODS: Active Demodex folliculorum were selected from patients with moderate to severe Demodex infestation. A total of 25 TCMs were individually extracted with 80% ethanol by heat under reflux, and then prepared to be concentration of 200 mg/ml. The extractions were used individually in mite-killing experiment in vitro to judge anti-mite activity by observing time of killing mites. Physiological saline and Radix Stemonae extraction were selected as blank control and positive control, respectively. RESULTS: The TCMs with average time of killing mites below 5 min were Cortex Phellodendri; Herba Taraxac, Herba Agrimoniae, Semen Hydnocarpi, Pericarpium Citri Reticulatae, Rhizoma Dioscoreae Hypoglaucae, Flos Genkwa and Radix Stemona. Among them, time with Cortex phellodendri, Herba Taraxac, Herba Agrimoniae, Semen Hydnocarpi and Pericarpium Citri Reticulatae was statistically shorter than that with Radix Stemonae (P < 0.05). CONCLUSION: Cortex Phellodendri, Herba Taraxac and Herba Agrimoniae et al. had remarkable anti-mite activities to Demodex folliculorum.

  Two pyrrolo[1,2-a]azepine type alkaloids from Stemona collinsae Craib: structure elucidations, relationship to asparagamine A, and a new biogenetic concept of their formation.:Chem Biodivers. 2004 Feb;1(2):265-79.Seger C, Mereiter K, Kaltenegger E, Pacher T, Greger H, Hofer O.Institute of Organic Chemistry, University of Vienna, W?hringerstrasse 38, A-1090 Vienna. christoph.seger@uibk.ac.at

 The alkaloids 1',2'-didehydrostemofoline (2) and 2'-hydroxystemofoline (3) from Stemona collinsae Craib (Stemonaceae) were studied by X-ray crystallography and NMR spectroscopy, and they are compared with the parent compound stemofoline (1). The X-ray analysis of the CH2Cl2 solvate of 2'-hydroxystemofoline (3) allowed the determination of the absolute configuration of this compound unequivocally, whereas optical rotation was used to infer the absolute configuration of 1',2'-didehydrostemofoline (2). Based on these results, it is shown that asparagamine A isolated from Asparagus racemosus Willd. (Asparagaceae) is identical to 1',2'-didehydrostemofoline obtained from S. collinsae Craib, and that the reported plant source of asparagamine A was most likely a Stemona species. In the context of the current investigations, a novel concept on the biosynthesis of Stemona alkaloids has been worked out and is presented here.


  Free-radical approaches to stemoamide and analogues.:J Org Chem. 2006 Dec 8;71(25):9528-31.Bogliotti N, Dalko PI, Cossy J.Laboratoire de Chimie Organique, associ¨¦ au CNRS, ESPCI, 10 rue Vauquelin, 75231, Paris Cedex 05, France.

 Two approaches allowing access to the tricyclic stemona backbone are presented. Both approaches rely on a free-radical cyclization reaction as the key step. In the formal synthesis of (+/-)-stemoamide, the construction of the A ring of the natural product was achieved via a 5-exo-trig radical cyclization with atom transfer. The two diastereoisomers issuing from this cyclization showed different reactivity while forming the seven-membered ring of the final product. In the second part of this study, a 7-exo-trig free radical cyclization was realized allowing access to the (+/-)-9,10-bis-epi-stemoamide. This reaction was highly stereoselective and allowed the control of three of the four contiguous stereocenters present in the molecule.

  Development of a pharmacodynamic screening model with Crithidia fasciculata.:Wien Klin Wochenschr. 2006;118(19-20 Suppl 3):42-9.Tasanor O, Engelmeier D, Brem B, Wiedermann-Schmidt U, Greger H, Wernsdorfer WH.Institute of Specific Prophylaxis and Tropical Medicine, Centre for Physiology and Pathophysiology, Medical University of Vienna, Austria. tasanor@yahoo.com

 The genus Crithidia is a member of the family Trypanosomatidae and is related to the genera Leishmania and Trypanosoma with which it shares a variety of biochemical mechanisms, such as polyamine synthesis and methionin salvage. In consequence, a screening system for antiparasitic candidate material has been developed with Crithidia fasciculata, a parasite naturally occurring in insects and amphibians, but devoid of pathogenicity for humans. Initially a variety of culture media were evaluated of which TPS was best suited for the maintenance of stock cultures, and E-medium - a newly developed formula - for sensitivity testing. Optimal growth of C. fasciculata was observed under microaerophilic conditions. A system for sensitivity testing was developed and applied to the investigation of extracts from higher tropical plants of the genera Stemona and Aglaia for anticrithidial activity. Extracts with significant anti-crithidial activity were scheduled for chromatographic fractionation and the subsequent isolation, purification and structural identification of individual compounds for further sensitivity testing. Encouraging results were obtained with extracts from Aglaia odorata leaves, A. elaeagnoidea stem bark and A. edulis leaves, with EC(90) values of 1213 ng/ml, 1606 ng/ml, and 1462 ng/ml, respectively.

  Stemoninines from the roots of Stemona tuberosa.:J Nat Prod. 2006 Jul;69(7):1051-4.Lin LG, Zhong QX, Cheng TY, Tang CP, Ke CQ, Lin G, Ye Y. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu-Chong-Zhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, People's Republic of China.

 Five new stemoninine-type alkaloids, bisdehydrostemoninine (1), isobisdehydrostemoninine (2), bisdehydroneostemoninine (3), and bisdehydrostemoninines A (4) and B (5), were isolated from the crude-alkaloid extract of the roots of Stemona tuberosa. Their structures were elucidated on the basis of one- and two-dimensional NMR and other spectroscopic studies. The relative configuration of 4 was determined by X-ray diffraction. Alkaloid 1 displayed significant antitussive activity in the citric acid-induced guinea pig cough model.

  Stilbenoids from Stemona japonica.:J Asian Nat Prod Res. 2006 Jan-Mar;8(1-2):47-53.Yang XZ, Tang CP, Ye Y.State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, SIBS, Chinese Academy of Sciences, 555 Zu-Chong-Zhi Road, Zhangjiang Hightech Park, Shanghai 201203, People's Republic of China.

 Three new dihydrostilbenes, stilbostemins J-L (1-3), and a new dihydrophenanthrene, stemanthrene F (4), were isolated from the roots of Stemona japonica together with two known bibenzyls, 3,5-dihydroxy-4-methylbibenzyl (5) and 3,5-dihydroxy-2'-methoxy-4-methylbibenzyl (6). Their structures were elucidated by spectroscopic analyses. Compounds 3-6 exhibited strong antibacterial activities against Staphylococcus aureus and Staphylococcus epidermidis.

  Antitussive effects of Stemona tuberosa with different chemical profiles.:J Ethnopharmacol. 2006 Nov 3;108(1):46-53. Epub 2006 May 4.Xu YT, Hon PM, Jiang RW, Cheng L, Li SH, Chan YP, Xu HX, Shaw PC, But PP.Department of Biology, Chinese University of Hong Kong, Shatin, N.T., Hong Kong, PR China.

 The root tubers of Stemona tuberosa, Stemona japonica and Stemona sessilifolia are recognized by the Pharmacopoeia of the People's Republic of China as authentic sources of the herb Radix Stemonae (Baibu). Careful anatomical analyses of these three species, whose identities were confirmed by flowering and fruiting samples, revealed that the root tubers of Stemona tuberosa could be distinguished from those of the other two species by the presence of scattered fibers in the cortex and pith and by the absence of thickened striations on the surface of velamen cells. HPLC analyses demonstrated that the total alkaloid profiles could be grouped into four types represented as the major component by stenine-type Stemona alkaloids such as tuberostemonine (4) and neotuberostemonine (3), or by non-stenine types such as croomine (1) and stemoninine (2). Nevertheless, all these samples demonstrated different degrees of antitussive properties in guinea pigs. These results suggested that non-stenine-type of Stemona alkaloids also contributed to the antitussive properties. The variations in chemical profiles among herb samples add difficulty in ensuring quality control in botanical products.


  Alkaloids and chemical diversity of Stemona tuberosa.:J Nat Prod. 2006 May;69(5):749-54.Jiang RW, Hon PM, Zhou Y, Chan YM, Xu YT, Xu HX, Greger H, Shaw PC, But PP.Institute of Chinese Medicine, Department of Biology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, People's Republic of China.

 Phytochemical investigation of the chemical components of Stemona tuberosa led to the isolation of two new alkaloids named tuberostemonine K (1) and tuberospironine (2), together with the known tuberostemonine (3). The new structures of 1 and 2 were elucidated through extensive spectroscopic analyses, while the molecular structure of 3 was confirmed by X-ray analysis. A gradient reversed-phase HPLC-ELSD method was established for the investigation of the chemical diversity of S. tuberosa from 13 localities, and four types of chemical variation featured by the major components 3, neotuberostemonine (4), croomine (5), and stemoninine (6), respectively, were observed.

  Neuroprotective bibenzyl glycosides of Stemona tuberosa roots.:J Nat Prod. 2006 Apr;69(4):679-81.

 Three new bibenzyl glycosides characterized as stilbostemin B 3'-beta-D-glucopyranoside (1), stilbostemin H 3'-beta-D-glucopyranoside (2), and stilbostemin I 2"-beta-D-glucopyranoside (3) were isolated from the roots of Stemona tuberosa. All three bibenzyl glycosides significantly protected human neuroblastoma SH-SY5Y cells from 6-hydroxydopamine-induced neurotoxicity.

  Screening for larvicidal activity in some Thai plants against four mosquito vector species.:Southeast Asian J Trop Med Public Health. 2005 Nov;36(6):1412-22.Komalamisra N, Trongtokit Y, Rongsriyam Y, Apiwathnasorn C.Department of Medical Entomology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. tmnkm@mahidol.ac.th

 Ninety-six ethanolic extracts from various parts of 84 Thai plant species were tested for their larvicidal activity against Aedes aegypti mosquitoes. Extracts from Rhinacanthus nasutus, Derris elliptica, Trigonostemon reidioides, Homalomena aromatica, Stemona tuberosa and Acorus calamus possessed high larvicidal activity, with LC50 values between 16.0 and 48.2 mg/l. Petroleum ether (PE) and methanol (MeOH) extracts were tested for their larvicidal activity against 4 mosquito vector species. The PE extract of R. nasutus exhibited larvicidal effects against Ae. aegypti, Culex quinquefasciatus, Anopheles dirus and Mansonia uniformis with LC50 values between 3.9 and 11.5 mg/l, while the MeOH extract gave LC50 values of between 8.1 and 14.7 mg/l. D. elliptica PE extract showed LC50 values of between 11.2 and 18.84 mg/l and the MeOH extract exhibited LC50 values between 13.2 and 45.2 mg/l.

  Intestinal absorption of Stemona alkaloids in a Caco-2 cell model.:Planta Med. 2006 Feb;72(3):211-6.Leung PH, Zhang L, Zuo Z, Lin G.Department of Pharmacology, The Chinese University of Hong Kong, Shatin, NT, SAR.

 The intestinal absorption of neotuberostemonine and neostenine, two major bioactive alkaloids of the commonly used antitussive traditional Chinese medicine Stemona tuberosa Lour, was investigated using a Caco-2 monolayer model. Both alkaloids exhibited a high absorptive permeability which was higher for neostenine [P(app(AB)) = 12.03 +/- 1.14 x 10 (-6) cm/s] than for neotuberostemonine [P(app(AB)) = 9.27 +/- 0.79 x 10 (-6) cm/s], indicating that they are likely to be well absorbed and orally active. Furthermore, both alkaloids were identified to be the substrates of P-glycoprotein and have a transport preference from the basolateral to apical direction with efflux ratios between 2 and 3. Cyclosporin A dose-dependently inhibited the secretory permeability of these alkaloids and abolished their active efflux transport.

  A short total synthesis of (+/-)-aspidospermidine.:Org Lett. 2006 Mar 2;8(5):831-4.Sharp LA, Zard SZ.Laboratoire de Synth¨¨se Organique associ¨¦ au CNRS, Ecole Polytechnique, 91128 Palaiseau, France.

 A cascade radical cyclization starting from an amidyl radical has been used for the construction of (+/-)-aspidospermidine. This approach has also been developed for the preparation of a tricycle whose framework is contained in the stemona alkaloids.


  Structural relationships, distribution and biological activities of stemona alkaloids.:Planta Med. 2006 Feb;72(2):99-113. Review.Greger H.Comparative and Ecological Phytochemistry Section, Institute of Botany, University of Vienna, Rennweg 14, 1030 Vienna, Austria. harald.greger@univie.ac.at

 Stemona alkaloids represent a unique class of natural products exclusively isolated from the monocotyledonous family Stemonaceae comprising three genera mainly distributed in southeast Asia. Structurally the alkaloids are characterised by a pyrrolo[1,2- a]azepine nucleus usually linked with two carbon chains mostly forming terminal lactone rings. Based on biosynthetic considerations and their various distribution the present review describes 82 Stemona alkaloids grouped into three skeletal types. Due to different carbon chains attached to C-9 of the pyrroloazepine nucleus they were classified into stichoneurine-, protostemonine- and croomine-type alkaloids. The genera Croomia and Stichoneuron only accumulate croomine or stichoneurine derivatives, respectively, whereas the genus Stemona produces all three types of alkaloids. However, species-specific accumulation trends towards certain structural types represent valuable chemosystematic criteria. Bioassays with larvae of Spodoptera littoralis exhibited very high insect toxicity for the roots of Stemona species containing certain protostemonine derivatives, especially didehydrostemofoline, whereas those with dominating stichoneurine or croomine derivatives showed low toxicity but sometimes remarkable repellence due to an accumulation of tuberostemonine. Tuberostemonine also showed effects on the motility of helminth worms and reduced the excitatory transmission at the crayfish neuromuscular junction. Significant antitussive activity was shown for the stereoisomeric neotuberostemonine in guinea-pig after cough induction by citric acid aerosol stimulation. Studies on structure-activity relationship with seven related compounds revealed that the saturated tricyclic pyrrolobenzazepine nucleus of tuberostemonines is the prerequisite for antitussive activity.

  Analyses of Stemona alkaloids in Stemona tuberosa by liquid chromatography/tandem mass spectrometry.:Rapid Commun Mass Spectrom. 2006;20(6):1030-8.Zhou Y, Jiang RW, Hon PM, Xu YT, Chan YM, Chan TW, Xu HX, Ding LS, But PP, Shaw PC.Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, PR China.

 Alkaloid profiles in Stemona tuberosa were found to be highly variable. Six Stemona alkaloids isolated from the plant were subjected to on-line high-performance liquid chromatography/electrospray ionization mass spectrometry (HPLC/ESI-MS) and tandem mass spectrometry (MS/MS) analyses. Their fragmentation patterns and products were useful for their characterization. The LC/MS fingerprints of these alkaloids, though variable among samples, could provide an overall characterization of the authenticity and quality of this species and help to differentiate it from S. japonica and S. sessilifolia, as all three species are recognized as genuine sources of the herb Radix Stemonae in the Pharmacopoeia of the People's Republic of China.

  Phytochemical studies on Stemona plants: isolation of stemofoline alkaloids.:J Nat Prod. 2005 Dec;68(12):1763-7.Sastraruji T, Jatisatienr A, Pyne SG, Ung AT, Lie W, Williams MC.Department of Chemistry, University of Wollongong, Wollongong, New South Wales 2522, Australia.

 Six new stemofoline alkaloids, (2'R)-hydroxystemofoline (5), (3'R)-stemofolenol (6), (3'S)-stemofolenol (7), 1',2'-didehydrostemofoline-N-oxide (8), the first C(19) stemofoline alkaloid, methylstemofoline (9), and the first glycosidated Stemona alkaloid, stemofolinoside (10), and three known alkaloids, (2'S)-hydroxystemofoline (2), (11Z)-1',2'-didehydrostemofoline (3), and (11E)-1',2'-didehydrostemofoline (4), have been isolated from a root extract of an unidentified Stemona species. The structure and relative configuration of these new alkaloids have been determined by spectral data interpretation and from semisynthetic studies.

  Isolation and chemotaxonomic significance of tuberostemospironine-type alkaloids from Stemona tuberosa.:Phytochemistry. 2006 Jan;67(1):52-7. Epub 2005 Nov 21.Jiang RW, Hon PM, Xu YT, Chan YM, Xu HX, Shaw PC, But PP.Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, PR China.

 An alkaloid named 6alpha-hydroxycroomine (1) as well as the known croomine (2), both belonging to the tuberostemospironine-alkaloid type, were isolated from Stemona tuberosa as the major components. The structure of 1 was elucidated through extensive spectroscopic analyses. Comparison of the HPLC profiles of the total alkaloids and the crude methanol extract showed that both compounds are naturally occurring. The first isolation of 1 and 2 from S. tuberosa has chemotaxonomic significance, confirming the close relationship between Stemona and Croomia. The trnL sequences of plants from the four genera of Stemonaceae cluster together as a clade, further lending support to retaining them in a single family.

  Iminosugar-producing Thai medicinal plants.:J Nat Prod. 2005 Aug;68(8):1238-42.

 Alpha-1-C-hydroxymethylfagomine (7), 3-O-beta-D-glucopyranosyl-DMDP (12), and 2,5-dideoxy-2,5-imino-D-glucitol (13) were isolated from the Thai traditional crude drug "Non tai yak" (Stemona tuberosa), which also contains a high concentration level of alpha-homonojirimycin (0.1% dry weight). "Thopthaep" (Connarus ferrugineus) and "Cha em thai" (Albizia myriophylla) contained 1-deoxymannojirimycin (DMJ) (10) at levels of 0.083% (dry weight) and 0.17% (dry weight), respectively. 2-O-alpha-D-Galactopyranosyl-DMJ (20), 3-O-beta-D-glucopyranosyl-DMJ (21), 1,4-dideoxymannojirimycin (17), 1,4-dideoxyallonojirimycin (18), and 1,4-dideoxyaltronojirimycin (19) from C. ferrugineus and 2-O-beta-D-glucopyranosyl-DMJ (22) and 4-O-beta-D-glucopyranosyl-DMJ (23) from A. myriophylla were isolated as new compounds.


  Studies on the synthesis of (+/-)-stenine: a combined intramolecular [4 + 2]-cycloaddition/rearrangement cascade.:J Org Chem. 2005 Jun 24;70(13):5197-206.Padwa A, Ginn JD.Department of Chemistry, Emory University, Atlanta, GA 30322, USA. chemap@emory.edu

 Several cyclic 2-(methylthio)-5-amidofurans containing tethered unsaturation were prepared via the reaction of dimethyl(methylthio)sulfonium tetrafluoroborate (DMSTF) with beta-alkoxy-gamma-dithiane lactams. Thermolysis of these furans resulted in an intramolecular Diels-Alder reaction (IMDAF). The resulting oxa-bridge cycloadducts underwent a subsequent 1,2-methylthio shift to form tricyclic lactams in high yield. Furan 9, annealed to an azepine ring, underwent the IMDAF reaction at or below room temperature. Conformational effects imposed by the placement of a carbonyl group within the tether, combined with a rotational bias about the C(2)-N bond, enhances the rate of the IMDAF reaction of the seven-ring system so that it occurs readily at 25 degrees C. The feasibility of using the cascade sequence in the context of a total synthesis of the Stemona alkaloid (+/-)-stenine was explored. The eventual synthesis of (+/-)-stenine was carried out by an intramolecular Diels-Alder reaction of a 2-amido-5-methylthio-substituted furan containing a trans-pent-3-enoic acid methyl ester side chain in order to create the desired azepinoindole skeleton. This was followed by a series of reductions to set the syn-anti stereochemical relationship at the incipient ring fusion sites present in stenine. All six stereocenters at the azepinoindole core were derived in high stereoselectivity from the functionality present in the rearranged cycloadduct 10. Compound 10 was converted to stenine in 11 additional steps via a sequence that features a Crabtree's-catalyst directed hydrogenation, iodolactonization, and a Keck allylation.

  Asymmetric synthesis of the azabicyclic core of the Stemona alkaloids.:J Org Chem. 2005 Apr 15;70(8):3157-67.Alib¨¦s R, Blanco P, Casas E, Closa M, de March P, Figueredo M, Font J, Sanfeliu E, Alvarez-Larena A.Departament de Qu¨ªmica and Unitat de Cristallografia, Universitat Aut¨°noma de Barcelona, 08193 Bellaterra, Spain.

 A general strategy for the construction of the 1-azabicyclo[5.3.0]decane core of Stemona alkaloids is developed. Our diversity-oriented approach exploits 1,3-dipolar cycloaddition of five-membered cyclic nitrones to C(6) olefins, followed by N-O reductive cleavage and azepine closure. The use of various enantiopure pyrroline N-oxides allows for a practical, stereoselective preparation of several putative precursors of different Stemona alkaloids.

  Inhibition of leukotriene biosynthesis by stilbenoids from Stemona species.:J Nat Prod. 2005 Jan;68(1):83-5.Adams M, Pacher T, Greger H, Bauer R. Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, A-8010 Graz, Austria.

 Fifteen stilbenoids and two alkaloids from Stemona collinsae, S. tuberosa, and S. peirrei were tested alongside the commercially available stilbenoids resveratrol and pinosylvin for inhibition of leukotriene formation in an ex vivo test system based on activated human neutrophilic granulocytes. The stilbenoids resveratrol (1), pinosylvin (2), dihydropinosylvin (3), stilbostemin A (4), stilbostemin B (5), stilbostemin D (6), stilbostemin F (7), stilbostemin G (8), stemofuran B (9), stemofuran C (10), stemofuran D (11), stemofuran G (12), stemofuran J (13), stemanthrene A (14), stemanthrene B (15), stemanthrene C (16), and stemanthrene D (17) showed structure-dependent activities with IC(50) values ranging from 3.7 to >50 microM. The alkaloids tuberostemonine (18) and neotuberostemonine (19) were inactive at a concentration of 50 microM.

  Asymmetric total syntheses of tuberostemonine, didehydrotuberostemonine, and 13-epituberostemonine.:J Am Chem Soc. 2005 Jan 12;127(1):225-35.Wipf P, Spencer SR.Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. pwipf@pitt.edu

 Detailed experimental approaches toward the pentacyclic Stemona alkaloids tuberostemonine and didehydrotuberostemonine and the close analogue 13-epituberostemonine are described. The syntheses originate with a hydroindolinone derivative that can be obtained on a large scale in a single step from carbobenzoxy-protected l-tyrosine. Highlights of the conversion of this hydroindolinone to the target structures are the three-fold use of ruthenium catalysts, first in azepine ring-closing metathesis and then in alkene isomerization and cross-metathesis propenyl-vinyl exchange, as well as the stereoselective attachment of a gamma-butyrolactone ring to a tetracycle core structure by use of a lithiated asymmetric bicyclo[3.2.1]octane (ABO) ortho ester. Structural analysis by density functional theory (DFT) methods revealed that the ease of oxidation of the natural product is likely due to the conformational preferences of the pyrrolidine and the fused cyclohexane rings.

  Synthesis of (-)-9,10-epi-stemoamide.:J Org Chem. 2004 Oct 29;69(22):7734-6.Khim SK, Schultz AG.Department of Chemistry, Rensselaer Polytechnic Institute, Troy, New York 12180, USA. seock-kyu_khim@berlex.com

 An efficient synthesis of (-)-9,10-epi-stemoamide has been accomplished in nine steps and 13% overall yield. The synthesis features a lithium hydroxide-promoted fragmentation and an intramolecular 7-exo-trig radical cyclization.


  Phytochemical studies on Stemona burkillii prain: two new dihydrostemofoline alkaloids.:J Nat Prod. 2004 Oct;67(10):1740-3.Mungkornasawakul P, Pyne SG, Jatisatienr A, Lie W, Ung AT, Issakul K, Sawatwanich A, Supyen D, Jatisatienr C.Department of Chemistry, University of Wollongong, New South Wales, 2522, Australia.

 Two new dihydrostemofoline alkaloids, 11(S),12(R)-dihydrostemofoline (3) and stemoburkilline (4), along with stemofoline (1) and 2'-hydroxystemofoline (2) have been isolated from a root extract of Stemona burkillii Prain. The structure and relative configuration of 3 have been determined via spectroscopic data and from comparison with synthetic 11(S),12(S)-dihydrostemofoline (5). The configuration of the exo-cyclic alkene group in 4 is tentively assigned as E on the basis of mechanistic considerations.

  Antioxidant dehydrotocopherols as a new chemical character of Stemona species.:Phytochemistry. 2004 Oct;65(19):2719-29.Brem B, Seger C, Pacher T, Hartl M, Hadacek F, Hofer O, Vajrodaya S, Greger H.Comparative and Ecological Phytochemistry Department, Institute of Botany, University of Vienna, Rennweg 14, A-1030 Wien, Austria.

 From the roots of various Stemona species four new dehydrotocopherols (chromenols) were isolated and their structures and stereochemistry elucidated by spectroscopic methods. The double bond between C-3 and C-4 proved to be a typical chemical character of the genus found in most of the species. Various C-methylations of the aromatic ring reflect differences in methyltransferase activities and agreed with the current species delimitations showing an exclusive accumulation of dehydro-delta-tocopherol for the Stemona tuberosa group, whereas different provenances of Stemona curtisii were characterized by dehydro-gamma-tocopherol accompanied by small amounts of dehydro-alpha-tocopherol. From Stemona collinsae all four tocopherols were isolated with a clear preponderance of dehydro-delta-tocopherol accompanied by smaller amounts of the rare dehydro-beta-tocopherol. Stemona burkillii and a group of unidentified species showed a weak accumulation trend towards dehydro-alpha-tocopherol, whereas Stemona cochinchinensis and especially Stemona kerrii clearly differed by a preponderance of chromanol derivatives. In Stemona cf. pierrei no tocopherols could be detected at all. Based on TLC tests and microplate assays with the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH*) the antioxidant capacities of all chromenol derivatives were comparable with that of alpha-tocopherol showing no significant differences among each other, except for a more rapid kinetic behaviour of the 5,7,8-methylated dehydro-alpha-tocopherol.

  Activity of novel plant extracts against medullary thyroid carcinoma cells.:Anticancer Res. 2004 Mar-Apr;24(2A):495-500.Rinner B, Siegl V, P¨¹rstner P, Efferth T, Brem B, Greger H, Pfragner R.Department of Pathophysiology, Medical University of Graz, Heinrichstrasse 31, A-8010 Graz, Austria.

 BACKGROUND: Medullary thyroid carcinoma (MTC) is a rare calcitonin-producing tumor, derived from the parafollicular C-cells of the thyroid. MTC is known to be relatively insensitive to conventional chemotherapy. MATERIALS AND METHODS: Eight cell lines were established from MTCs; each showed an up-regulation of Bcl-2. We investigated ten agents from plants of the genera Stemona (Stemonaceae), Aglaia (Meliaceae) and Artemisia (Asteraceae) for their effects on proliferation and apoptotic rates. Extracts have been used in traditional Chinese medicine; however, no experience on their effects on medullary thyroid carcinomas has been reported so far. Growth kinetics and viability were examined using the Casy-1-Cell Counter & Analyzer and the WST-1-based cytotoxicity assay. Apoptosis was studied by DAPI staining, by measurement of caspase-3 activity and Bcl-2 expression. RESULTS: A strong antiproliferative effect was recognized in each Aglaia species and with Artesunate, whereas an enhancement of apoptosis was provoked particularly by Stemona tuberosa Lour. CONCLUSION: The activity of the novel plant extracts possiby offers a new approach towards successful chemotherapy of the so far chemo-resistant medullary thyroid carcinoma.

  Phytochemical and larvicidal studies on Stemona curtisii: structure of a new pyrido[1,2-a]azepine Stemona alkaloid.:J Nat Prod. 2004 Apr;67(4):675-7.Mungkornasawakul P, Pyne SG, Jatisatienr A, Supyen D, Jatisatienr C, Lie W, Ung AT, Skelton BW, White AH.Division of Environmental Sciences, Chiang Mai University, Chiang Mai 50202, Thailand.

 A new pentacyclic Stemona alkaloid, stemocurtisinol (3), with a pyrido[1,2-a]azepine A,B-ring system, and the known pyrrolo[1,2-a]azepine alkaloid oxyprotostemonine (4) have been isolated from a root extract of S. curtisii. The structure and relative stereochemistry of stemocurtisinol was determined by spectral data interpretation and X-ray crystallography. This compound is a diastereoisomer of oxystemokerrin and has the opposite configuration at C-4 and C-19. The individual alkaloid components showed significant larvicidal activity (IC(50) 4-39 ppm) on mosquito larvae (Anopheles minimus HO).

  Dihydrophenanthrenes and other antifungal stilbenoids from Stemona cf. pierrei.:Phytochemistry. 2004 Jan;65(1):99-106.Kostecki K, Engelmeier D, Pacher T, Hofer O, Vajrodaya S, Greger H.Comparative and Ecological Phytochemistry Department, Institute of Botany, University of Vienna, Rennweg 14, A-1030, Wien, Austria.

 Three new dihydrophenanthrenes, stemanthrenes A-C, along with the new dihydrostilbene stilbostemin G were isolated and identified from the underground parts of Stemona cf. pierrei together with the known pinosylvin, 4'-methylpinosylvin, dihydropinosylvin, stilbostemins B, D, and E as well as the pyrrolo[1,2-a]azepine alkaloids protostemonine and stemonine. The structures of all new stilbenoids, elucidated by NMR analyses, showed a common substitution pattern for aromatic ring A and characteristic C-methylations for ring B. The trivial name racemosol, previously reported for S. collinsae, was renamed to stemanthrene D due to its priority for another compound. Bioautographic tests on TLC plates with Cladosporium herbarum displayed high antifungal activity for compounds with an unsubstituted aromatic ring A, e.g. pinosylvin, but only weak effects for the higher substituted stilbostemin G and stemanthrenes A-C. Similar results were obtained by germ tube inhibition of five microfungi using 2-fold serial broth dilutions determined by a microplate reader. Because of weak inhibition and chemical instability of stemanthrenes, no EC(50) and EC(90) values could be calculated.


  Antitussive activity of Stemona alkaloids from Stemona tuberosa.:Planta Med. 2003 Oct;69(10):914-20.Chung HS, Hon PM, Lin G, But PP, Dong H. Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR.

 Bioactivity-directed fractionation of the crude extract of Stemona tuberosa led to the isolation and characterization of four new stenine-type Stemona alkaloids, namely tuberostemonine J ( 2), tuberostemonine H ( 3), epi-bisdehydrotuberostemonine J ( 4) and neostenine ( 5), together with the known neotuberostemonine ( 1). These five isolated alkaloids were examined for antitussive activity in guinea pig after cough induction by citric acid aerosol stimulation. In this report, we demonstrated, for the first time, that compounds 1 and 5 showed significant antitussive activities. Further study of the structure-activity relationship on these isolated alkaloids and two synthetic analogues revealed that the saturated tricyclic pyrrolo[3,2,1- jk] benzazepine nucleus is the primary key structure contributing to the antitussive activity and all cis configurations at the three ring junctions are the optimal structure for the antitussive activity of stenine-type Stemona alkaloids.

  Total synthesis of (-)-stemonine.:Org Lett. 2003 Sep 4;5(18):3361-4.Williams DR, Shamim K, Reddy JP, Amato GS, Shaw SM.Department of Chemistry, Indiana University, 800 East Kirkwood Avenue, Bloomington, Indiana 47405-7102, USA. williamd@indiana.edu

 An enantioselective total synthesis of (-)-stemonine (1) is reported via a convergent assembly of the acyclic precursor 2. Key transformations include a Staudinger-aza-Wittig reaction to form the central perhydroazepine ring system and an iodine-induced tandem cyclization to construct the pyrrolidino-butyrolactone framework.

  Stemocurtisine, the first pyrido[1,2-a]azapine Stemona alkaloid:J Nat Prod. 2003 Jul;66(7):980-2.Mungkornasawakul P, Pyne SG, Jatisatienr A, Supyen D, Lie W, Ung AT, Skelton BW, White AH.Division of Environmental Sciences, Chiang Mai University, Chiang Mai 50202, Thailand.

 A new pentacyclic stemona alkaloid, stemocurtisine (2), with a novel pyrido[1,2-a]azapine A,B-ring system, has been isolated from a root extract of Stemona curtisii. The structure and relative stereochemistry was determined by spectral data interpretation and X-ray crystallography.

  Insecticidal pyrido[1,2-a]azepine alkaloids and related derivatives from Stemona species.:Phytochemistry. 2003 Aug;63(7):803-16.Kaltenegger E, Brem B, Mereiter K, Kalchhauser H, K?hlig H, Hofer O, Vajrodaya S, Greger H.Comparative & Ecological Phytochemistry Department, Institute of Botany, University of Vienna, Rennweg 14, A-1030 Vienna, Austria.

 Eight new alkaloids, the pyrido[1,2-a]azepines stemokerrin, methoxystemokerrin-N-oxide, oxystemokerrin, oxystemokerrin-N-oxide, and pyridostemin, along with the pyrrolo[1,2-a]azepines dehydroprotostemonine, oxyprotostemonine, and stemocochinin were isolated from four Stemona species together with the known compounds protostemonine, stemofoline, 2'-hydroxystemofoline, and parvistemonine. Their structures were elucidated by 1H and 13C NMR including 2D methods and two key compounds additionally by X-ray diffraction. Besides the formation of a six membered piperidine ring, additional oxygen bridges and N-oxides contributed to structural diversity. The co-occurrence of pyrrolo- and pyridoazepines suggested biosynthetic connections starting from more widespread protostemonine type precursors. Bioassays with lipophilic crude extracts against Spodoptera littoralis displayed very strong insecticidal activity for the roots of S. curtisii and S. cochinchinensis, moderate activity for S. kerrii, but only weak effects for the unidentified species HG 915. The insect toxicity was mainly caused by the accumulation of stemofoline, oxystemokerrin, and dehydroprotostemonine displaying two different modes of action. Based on the various insecticidal activities of 13 derivatives structure-activity relationships became apparent.

  Feeding deterrence and contact toxicity of Stemona alkaloids-a source of potent natural insecticides.:J Agric Food Chem. 2002 Oct 23;50(22):6383-8.Brem B, Seger C, Pacher T, Hofer O, Vajrodaya S, Greger H.Comparative and Ecological Phytochemistry Department, Institute of Botany, University of Vienna, Rennweg 14, A-1030 Wien, Austria.

 On the basis of chronic feeding bioassays with neonate larvae of Spodoptera littoralis reared on an artificial diet, the methanolic leaf and root extracts from Stemona collinsae displayed very high insect toxicity compared to those of two Aglaia species, a commercial Pyrethrum extract, and azadirachtin, whereas S. tuberosa extracts demonstrated low activity in roots and no activity in leaves. Beyond that, in leaf disk choice tests against fifth instar larvae, S. collinsae showed strong antifeedant activity, whereas S. tuberosa was characterized by remarkable repellency. The anti-insect properties of both species were based on pyrrolo[1,2-a]azepine alkaloids, from which didehydrostemofoline (asparagamine A) was the major compound of the roots of S. collinsae, exhibiting the highest toxicity in feeding assays. Saturation and hydroxylation of the side chain in the co-occurring stemofoline and 2'-hydroxystemofoline, respectively, led to an increasing loss of activity. Contact toxicity tests with stemofoline and didehydrostemofoline exhibited even higher activities than those of Pyrethrum extract. Tuberostemonine was the dominating alkaloid in the roots of S. tuberosa, showing outstanding repellency but no toxic effects.


  Antifungal stilbenoids from Stemona collinsae.:J Nat Prod. 2002 Jun;65(6):820-7.Pacher T, Seger C, Engelmeier D, Vajrodaya S, Hofer O, Greger H.Comparative and Ecological Phytochemistry Department, Institute of Botany, University of Vienna, Rennweg 14, A-1030 Wien, Austria.

 Fifteen new stilbenoids including 11 phenylbenzofurans, the stemofurans A-K (1-11), and four dihydrostilbenes, the stilbostemins A (15), C (17), E (19), and F (20), were isolated and identified from a methanolic extract of Stemona collinsae roots together with five known derivatives, the stilbenes pinosylvin (13) and 4'-methylpinosylvin (14), the dihydrostilbenes, stilbostemins B (16) and D (18), and the dihydrophenanthrene racemosol (12) as well as (+)-sesamin, coniferyl alcohol, and stigmasterol. Bioautographic tests with Cladosporium herbarum displayed antifungal activity for stilbenoids of all four structural types. Ten derivatives were tested against five microfungi using the microdilution technique linked with digital image analysis of germ tubes.

  Alkaloids from Stemona collinsae.:J Asian Nat Prod Res. 2002 Jun;4(2):81-5.Pham HD, Yu BW, Chau VM, Ye Y, Qin GW.Institute of Natural Products Chemistry, National Center of Sciences and Technology of Vietnam, Hanoi.

 A new alkaloid, isostenine (1), together with two known ones neotuberostemonine (2) and bisdehydroneotuberostemonine (3) were isolated from the root of Stemona collinsae. Their structures were determined by various spectral methods.

  A synthetic approach to the Stemona alkaloids.:J Org Chem. 2001 Nov 16;66(23):7751-6.Hinman MM, Heathcock CH.Center for New Directions in Organic Synthesis, Department of Chemistry, University of California, Berkeley, CA 94720, USA.

 This paper describes our work developing a strategy for the construction of the typical core structure of the Stemona alkaloids. The approach is to control the relative stereochemistry of the groups on the core 1-azabicyclo[5.3.0]decane ring system by a [3,3] sigmatropic rearrangement of an acylimmonium ion followed by selective reduction. After optimization, this reaction sequence afforded the desired diastereomer in 62% yield. Further efforts were directed toward elaboration of the characteristic butyrolactone substituent.

  Stereocontrolled total synthesis of the Stemona alkaloid (-)-stenine.:Chemistry. 2001 Oct 1;7(19):4107-16.

 The Stemona alkaloid stenine (1), isolated from Stemona tuberosa of physiologically active stemonaceous plants, possesses the structurally novel and unique azepinoindole skeleton (B,C,D-ring system). We have achieved the asymmetric total synthesis of (-)-stenine (1), starting from 1,5-pentanediol (10). The key features are an intramolecular diastereoselective Diels-Alder reaction of the (E,E,E) triene 6, prepared in a convergent fashion from three components--dienyl chloride 7, dithiane 8, and chiral phosphonate 9--and efficient construction of the tricyclic A,B,D-ring system 29 through thermodynamically controlled regioselective enolization of the bicyclic ketone 25. In this article, we describe in detail the highly stereocontrolled total synthesis of (-)-stenine (1). These results should be useful for the asymmetric total synthesis of another, more complex. molecule: tuberostemonine (2), the synthesis of which has never been reported.

  Occurrence of the insecticidal 16,17-didehydro-16(E)-stemofoline in Stemona collinsae.:Phytochemistry. 2001 Apr;56(7):693-5.Jiwajinda S, Hirai N, Watanabe K, Santisopasri V, Chuengsamarnyart N, Koshimizu K, Ohigashi H.Central Laboratory and Greenhouse Complex, Kasetsart University, Nakhon-Pathom, Thailand. rdiswj@nontri.ku.ac.th

 The occurrence of two alkaloids, 16,17-didehydro-16(E)-stemofoline and its isomer at C-4, 16,17-didehydro-4(E)-16(E)-stemofoline, were found together with a known insecticidal compound, stemofoline, in Stemona collinsae. The 16,17-didehydro-16(E)-stemofoline displayed higher insecticidal and antifeedant activities against the diamondback moth larvae than stemofoline.


  Recent advances on bioactive natural products from Chinese medicinal plants.:Med Res Rev. 1998 Nov;18(6):375-82. Review.Qin GW, Xu RS.Shanghai Institute of Materia Medica, Chinese Academy of Sciences, People's Republic of China. gwqin@server.shcnc.ac.cn

 China has accumulated a rich body of empirical knowledge of the use of medicinal plants for the treatment of various diseases throughout its long history. Chemical studies on Chinese medicinal plants provide a valuable material base for the discovery and development of new drugs of natural origin. In this article recent chemical work on various Chinese medicinal plants is reviewed, including Mussaenda pubescens (Rubiaceae), Isatis indigotica (Cruciferae), Euphorbia fischeriana, and E. ebracteolata (Euphorbiaceae), and Stemona species (Stemonaceae). The structural diversity of the medicinal chemical constituents of the above plants is discussed.

  Bibenzyls from Stemona tuberosa.:Phytochemistry. 1995 Feb;38(3):711-3.Zhao W, Qin G, Ye Y, Xu R, Le X.Shanghai Institute of Material Medica, Chinese Academy of Sciences.

 Three new bibenzyls were isolated from the roots of Stemona tuberosa. Their structures were identified by spectroscopic methods as 3,5-dihydroxy-4-methylbibenzyl, 3,5-dihydroxy-2'-methoxy-4-methylbibenzyl and 3-hydroxy-2',5-dimethoxy-2-methylbibenzyl.

  Pharmacognostical studies on Baibu radix stemonae and allied drugs. IX. Determination and evaluation of total alkaloid content in the roots of Chinese Stemona spp.:Yao Xue Xue Bao. 1992;27(7):556-60. Chinese.Cong XD, Xu GJ, Jin RL, Zhi HJ.Department of Pharmacognosy, China Pharmaceutidcal University, Nanjing.

 An acid-dye colorimetric method was reported for the determination of total alkaloids in 53 samples of Baibu drugs from their growing destricts in 14 provinces and municipalities and its average recovery and its linear range were 96.1% (CV less than 4%) and 20-150 micrograms respectively. The relationship between the total alkaloid content, geographical origins and morphology were discussed. The results showed that: 1. the content of total alkaloids of stemona was 0.26-3.1%; 2. that of Stemona sessilifolia was 0.26-2.17% with the highest content of the sample from Nanyang country in Henan Province; 3. that of S. japonica was 0.83-1.43%; 4. that of S. tuberosa was 0.53-3.1% with the highest content of sample from Hengyang in Hunan Province; 5. that of S. parviflora was 0.22-0.74% with the highest content of sample from Qongzhong in Hainan Province; and 6. that of more yellow, solider and stronger samples was higher than that of any other samples. However, that of all bigger samples in shape was not higher than that of smaller ones.


  Scientific References:

  1.Research Update:Stemona root.