Synthesis of Bis(indole) Alkaloids from Arundo donax: The Ynindole Diels–Alder Reaction,Conformational Chirality,and Absolute Stereochemistry

Bis(indole) alkaloids from Arundo donax were synthesized using the first ynindole Diels–Alder reaction. The alkaloids are chiral, having stable enantiomeric conformations with half‐lives of racemization of t_1/2=4150–25100 seconds at room temperature. Their absolute stereochemistry was determined using the exciton chirality method.     

Identification and analysis of alkaloids in cortex Phellodendron amurense by high‐performance liquid chromatography with electrospray ionization mass spectrometry coupled with photodiode array detection

Alkaloids from Cortex Phellodendron amurense Rupr. were identified to determine the material basis for the bioactivity of this herb. HPLC–ESI‐MS with photodiode array detection coupled to XCharge C₁₈ column was applied to analyze the alkaloids qualitatively and quantitatively. A total of 37 alkaloids were identified and tentatively characterized from the ethanol extract by online ESI‐MSⁿ fragmentation and UV spectral analysis. A total of ten alkaloids, including four novel natural products, were tentatively identified for the first time in P. amurense. The fragmentation pathways for certain compounds were analyzed. The contents of a pair of isomers (columbamine and jatrorrhizine) and four main alkaloids (phellodendrine, magnoflorine, berberine, and palmatine) were simultaneously quantified using the aforementioned method. Results showed that the newly discovered and known components of P. amurense were helpful in determining the material basis for the bioactivity of the herb. The application of the XCharge C₁₈ column is a suitable and practical method for the isolation of alkaloids in plants.     

Monoterpenoid Indole Alkaloids Bearing an N4‐Iridoid from Gelsemium elegans

Five new alkaloids, gelseganines A–D ( 1 – 4 ) and humantenine N₄‐oxide ( 5 ), were isolated from the stems and leaves of Gelsemium elegans. Compounds 1 – 4 represent a rare class of monoterpenoid indole alkaloids that bear an N₄‐iridoid unit. The structures of 1 – 5 were determined by spectroscopic analysis, single‐crystal X‐ray diffraction, and chemical correlation, and their absolute configurations were elucidated by CD analysis. A plausible biogenetic pathway for alkaloids 1 – 5 was also postulated.     

Three New C19‐Diterpenoid Alkaloids from Aconitum hemsleyanum var. circinatum

Further phytochemical investigation of the roots of Aconitum hemsleyanum var. circinatum resulted in the isolation of three new aconitine‐type C₁₉‐diterpenoid alkaloids, hemsleyanines E–G ( 1 – 3 , resp.). The structures of these new alkaloids were elucidated on the basis of spectral data including 2D‐NMR.     

New Diterpenoid Alkaloids from Aconitum liangshanicum

One new C₁₉‐diterpenoid alkaloid, named liangshantine ( 1 ), and three new C₂₀‐diterpenoid alkaloids, liangshansines A–C ( 2 – 4 , resp.), as well as eight known compounds, were isolated from the roots of Aconitum liangshanicum. The structures of these new alkaloids were elucidated by spectroscopic methods.     

NMR determination of pKa values of indoloquinoline alkaloids

Malaria is one of the most serious global health problems. Isolating new therapeutic agents with potential antimalarial activity from natural sources or preparing such agents either semisynthetically or synthetically is one strategy for solving the problem of resistance constantly evolving to the drugs currently in use. For alkaloids, the acid–base dissociation constant, pK_a, is an important characteristic, thought to be associated with biological activity. In this contribution, pK_a values for several indoloquinoline alkaloids were determined by using ¹H NMR spectroscopy in a mixture of solvents. The data were recalculated for water solutions using the correction factors reported previously. The structural dependence of the pK_a values for cryptolepine and its isomers neocryptolepine, isocryptolepine and isoneocryptolepine as well as some substituted neocryptolepine derivatives is discussed. Copyright © 2009 John Wiley & Sons, Ltd.     

Enantioselective Synthesis of Glutarimide Alkaloids Cordiarimides A,B, Crotonimides A,B, and Julocrotine

Five glutarimide alkaloids cordiarimide A ( 5 ), cordiarimide B ( 6 ), crotonimide A ( 3 ), crotonimide B ( 4 ), and julocrotine ( 2 ) have been synthesized starting from Boc‐L‐glutamine ( 7 ). The benzylic alcohol chiral centre of cordiarimides B ( 6 ) has been established in 6:1 diastereoselectivity by catalytic asymmetric hydrogenation using Zhou's catalytic system Pd(CF₃CO₂)₂/(R,R)‐Me‐DuPhos.     

Simultaneous determination of pyrroquinazoline alkaloids and flavonoids in Adhatoda beddomei and Adhatoda vasica and their marketed herbal formulations using ultra‐high‐performance liquid chromatography coupled with triple quadrupole linear ion trap mass spectrometry

Adhatoda beddomei and Adhatoda vasica leaf, known as ‘Vasaka ’ and/or ‘Vasa ’ in Ayurveda and ‘Malabar nut’ in English, is an official drug in the Indian Pharmacopoeia . The medicinal properties of these plants are due to the presence of pyrroquinazoline alkaloids. An UHPLC–ESI/MS/MS method in both positive and negative electrospray ionization in multiple‐reaction‐monitoring mode was developed and validated for the estimation of alkaloids and flavonoids in Adhatoda species and their marketed herbal formulations. Chromatographic separation was achieved on an Acquity UPLC® BEH C₁₈‐column using a gradient elution with 0.1% formic acid in water and methanol. The developed method was validated as per International Conference on Harmonization guidelines and found to be accurate with overall recovery in the range 94.2–105.0% (RSD ≤ 1.71%), precise (RSD ≤ 3.44%) and linear (R ² ≥ 0.9992) over the concentration range of 0.5–1000 ng/mL. The total content of alkaloids and flavonoids were highest in the chloroform and aqueous fraction of A. vasica leaf, respectively. The results indicated that the developed method was simple, rapid, sensitive, selective and accurate for the estimation of multiple bioactive constituents in crude mixture, and therefore could make a contribution to the quality control of Adhatoda species and its derived herbal formulations.     

微量热法比较黄连中四种生物碱的抗菌作用

采用微量热法研究和比较中药黄连中四种生物碱(BAs)的抗菌(大肠杆菌)作用。这四种生物碱分别为小檗碱、黄连碱、巴马汀和药根碱。用LKB-2277生物活性检测系统,以停留法测定了37 ℃时大肠杆菌在BAs作用下的热流功率-时间曲线,并记录生长速率常数k, 指数生长期和稳定期的最大热功率Pm, log、Pm, stat, 生长抑制率I, 传代时间tg,指数生长期的总产热量Qt, log,半数抑菌浓度IC50等热动力学参数。结果显示这四种生物碱具有相异的抗大肠杆菌生长代谢的作用,k, Pm, log和Qt, log值随BAs浓度的增加而相应的减少。综合分析k, Pm, log, Qt, log, I 和IC50值可以看出,BAs抑制大肠杆菌生长代谢强度按小檗碱、黄连碱、巴马汀、药根碱的顺序依次减弱。构效关系研究表明,母环C-2和C-3上连接的亚甲二氧基比甲氧基更能显著增强相应化合物的抗菌作用,而C-9和C-10上连接的亚甲二氧基或甲氧基对这种抗菌作用影响不大。     

Quantitative determination of isoquinoline alkaloids and chlorogenic acid in Berberis species using ultra high performance liquid chromatography with hybrid triple quadrupole linear ion trap mass spectrometry

Berberis species are well known and used extensively as medicinal plants in traditional medicine. They have many medicinal values attributable to the presence of alkaloids having different pharmacological activities. In this study, a method was developed and validated as per international conference on harmonization guidelines using ultra high performance liquid chromatography with hybrid triple quadrupole‐linear ion trap mass spectrometry operated in the multiple reaction monitoring mode for nine bioactive compounds, including protoberberine alkaloids, aporphine alkaloids and chlorogenic acid. This method was applied in different plant parts of eight Berberis species to determine variations in content of nine bioactive compounds. The separation was achieved on an ACQUITY UPLC CSH? C₁₈ column using a gradient mobile phase at flow rate 0.3 mL/min. Calibration curves for all the nine analytes provided optimum linear detector response (with R² ≥0.9989) over the concentration range of 0.5–1000 ng/mL. The precision and accuracy were within RSDs ≤2.4 and ≤2.3%, respectively. The results indicated significant variation in the total contents of the nine compounds in Berberis species.     

12-Molybdophosphoric Acid as an Analytical Reagent for Greater Celandine (Celadonium) Alkaloids

The conditions for determining the total greater celandine alkaloids resulting from a plant by acid infusion were studied. The interaction between the organic cations of alkaloids and the heteropoly anion PMo₁₂O^3- ₄₀ with the formation of a sparingly soluble stable associate of total celandine alkaloids was examined using UV and IR spectroscopy and quantum-chemical calculations. The associate composition (Alk)₃PMo₁₂O₄₀ was found by amperometric titration, and the ionic solubility product was calculated to be equal to (3.0 ± 0.2) × 10^–27 at P = 0.95 and n = 5. The synthesized associate was used as an electrode-active substance in the development of an ion-selective electrode with a plasticized membrane that is reversible and selective for the organic cations of greater celandine alkaloids. Procedures for determining total alkaloids in extracts, infusions, and medicinal forms were developed using potentiometry with ion-selective electrodes and amperometric titration.     

Analysis of Amaryllidaceae alkaloids from Crinum by high‐performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry

A high‐performance liquid chromatography/electrospray ionization multi‐stage tandem mass spectrometry (HPLC/ESI‐MSⁿ) method was developed to analyze two structurally related groups of Amaryllidaceae alkaloids (AmAs), crinane‐ and tazettine‐type alkaloids, in the species Crinum latifolium and C. asiaticum, as well as different organs of C. latifolium. In ESI‐MSⁿ spectra of the two types of alkaloids, characteristic fragmentation reactions were observed that allowed us to determine and differentiate them. Based on the fragmentation rules of reference standards, crinane‐type alkaloids displayed concurrent neutral loss of C₂H₅N (43 u) and C₂H₆N (44 u) as well as characteristic ions of m/z 213 and 211, whereas tazettine‐type alkaloids exhibited neutral loss of C₃H₇N (57 u) [or C₂H₅N (43 u), C₃H₇NO (73 u)] from the [M+H]⁺ and [M+H–H₂O]⁺ ions. These were supported by quadrupole time‐of‐flight (Q‐Tof)‐MS/MS analysis. The chemical complexity of the mixture was resolved by profiling. The compositions of the main crinane‐ and tazettine‐type alkaloids in the above‐mentioned species and organs were also compared. Overall, 28 AmAs comprising 14 crinane‐type and 14 tazettine‐type alkaloids were identified and studied by MS. Among them, 14 AmAs were tentatively characterized from the two species for the first time. This method allowed a rapid analysis of alkaloid distribution and composition of Crinum species, and may also be used for quality control and screening of extracts designated for pharmaceutical application. Copyright © 2009 John Wiley & Sons, Ltd.     

Highly Enantioselective Tandem Michael Addition of Tryptamine‐Derived Oxindoles to Alkynones: Concise Synthesis of Strychnos Alkaloids

A highly enantioselective tandem Michael addition of tryptamine‐derived oxindoles to alkynones was developed by taking advantage of a chiral N,N′‐dioxide Sc(OTf)₃ catalyst. The reaction enables the facile preparation of enantioenriched spiro[pyrrolidine‐3,3′‐oxindole] compounds, which provides a novel strategy for the synthesis of monoterpenoid indole alkaloids. As a demonstration, the asymmetric synthesis of strychnos alkaloids [(?)‐tubifoline, (?)‐tubifolidine, (?)‐dehydrotubifoline] was achieved in 10–11 steps.     

Unguiculins A-C: cytotoxic bis-guanidine alkaloids from the French Polynesian sponge,Monanchora n. sp

Two new acyclic bis-guanidine alkaloids, unguiculins B-C (2–3), were isolated from a French Polynesian sponge Monanchora n. sp. together with the known compound unguiculin A (1). Their structures were established by spectroscopic data interpretation and comparison with the literature. Unguiculins A-C displayed antiproliferative and cytotoxic efficacy against several human cancer cells with IC₅₀ values in the micromolar range.     

Three New Alkaloids,Paxiphyllines C – E,from Daphniphyllum paxianum

Nine Daphniphyllum alkaloids, including three new ones, paxiphyllines C–E ( 1 – 3 , resp.), were isolated from the twigs and the leaves of Daphniphyllum paxianum. Paxiphylline C ( 1 ) represents the first example of Daphniphyllum alkaloids with a carbonyldioxy group. Their structures were elucidated on the basis of spectroscopic data.     

Preparative isolation of alkaloids from Corydalis bungeana Turcz. by high-speed counter-current chromatography using stepwise elution

High‐speed counter‐current chromatography (HSCCC) was successfully applied for the preparative separation and purification of alkaloids from Corydalis bungeana Turcz. (Kudiding in Chinese) for the first time. After the measurement of partition coefficient of seven target alkaloids in the nine two‐phase solvent systems composed of CHCl₃–MeOH–(0.1 M; 0.2 M; 0.3 M) HCl (4:1.5:2; 4:2:2; 4:3:2, v/v), CHCl₃–MeOH–0.2 M HCl (4:2:2, v/v) and CHCl₃–MeOH–0.3 M HCl (4:3:2, v/v) were finally selected for the HSCCC separation using the first upper phase as the stationary phase and the stepwise elution of the two lower mobile phases. Consequently, sanguinarine (10 mg), corynoline (25 mg), protopine (20 mg), corynoloxine (18 mg), and 12‐hydroxycorynoline (8 mg) were obtained from 200 mg of crude alkaloid extracts with purities of 94–99% as determined by HPLC. Their chemical structures were characterized on the basis of ¹H‐NMR, ¹³C‐NMR, and LC‐ESI‐Q‐TOF‐MS/MS analyses.     

Pregnane‐Type Steroidal Alkaloids of Sarcococca saligna: a New Class of Cholinesterase Inhibitors

Phytochemical investigation of Sarcococca saligna by extensive bioassay‐guided fractionation resulted in the isolation of the pregnane‐type steroidal alkaloids 1 – 15 , i.e. of the five new compounds 1 – 5 and the ten known alkaloids 6 – 15 . The structures of the new alkaloids salignenamide C ( 1 ), salignenamide D ( 2 ), 2β‐hydroxyepipachysamine D ( 3 ), salignenamide E ( 4 ), and salignenamide F ( 5 ) were elucidated with the help of modern spectroscopic techniques, while the known alkaloids axillarine C ( 6 ), axillarine F ( 7 ), sarcorine ( 8 ), N³‐demethylsaracodine ( 9 ), saligcinnamide ( 10 ), salignenamide A ( 11 ), vaganine A ( 12 ), axillaridine A ( 13 ), sarsalignone ( 14 ), and sarsalignenone ( 15 ) were identified by comparing their spectral data with those reported earlier. Inhibition of electric‐eel acetylcholinesterase (EC 3.1.1.7) and horse‐serum butyrylcholinesterase (EC 3.1.1.8) by alkaloids 1 – 15 were investigated. These new cholinesterase inhibitors may act as potential leads in the discovery of clinically useful inhibitors for nervous‐system disorders, particularly by reducing memory deficiency in Alzheimer's disease patients by potentiating and effecting the cholinergic transmission process. These compounds were found to inhibit both enzymes in a concentration‐dependent fashion with the IC₅₀ values ranging from 5.21–227.92 μM against acetylcholinesterase and 2.18–38.36 μM against butyrylcholinesterase.     

Preparative separation of isoquinoline alkaloids from Corydalis impatiens using a middle‐pressure chromatogram isolated gel column coupled with two‐dimensional liquid chromatography

We established a two‐dimensional strong cation exchange/reversed‐phase liquid chromatography protocol to isolate and purify isoquinoline alkaloids from Corydalis impatiens. Isoquinoline alkaloids were first enriched from a C. impatiens extract in which liposoluble components were removed using a medium‐pressure chromatographic tower containing middle chromatogram isolated gel. A strong cation exchange column was employed to separate and obtain 30 fractions. We chose fractions 22–29 for reversed‐phase liquid chromatography purification using characteristic isoquinoline alkaloid ultraviolet absorption spectra. Several isoquinoline alkaloid fractions (22–29) were further separated, and those of low resolution were isolated via two‐dimensional liquid chromatography in the orthogonal plane. A total of eight novel isoquinoline alkaloids with characteristic ultraviolet spectra were obtained from C. impatiens. We thus demonstrate the benefits of off‐line two‐dimensional strong cation exchange/reversed‐phase liquid chromatography to isolate isoquinoline alkaloids from C. impatiens.     

Evollionines A–C,Three New Alkaloids Isolated from the Fruits of Evodia rutaecarpa

A phytochemical study of the CHCl₃ extract of the dried unripe fruits of Evodia rutaecarpa (Juss. ) Benth. (Rutaceae) resulted in the isolation of three new alkaloids, evollionines A–C ( 1 – 3 , resp.), together with two known compounds, evodianinine and wuzhuyumide I. The structures of the new compounds were elucidated on the basis of detailed spectroscopic evidence and confirmed in the case of compound 1 by single‐crystal X‐ray analysis.