Selective separation of structure-related alkaloids in Rhizoma coptidis with "click" binaphthyl stationary phase and their structural elucidation with liquid chromatography-mass spectrometry

It is a new task to separate structure-related compounds into a fraction according to their structural characteristics in a complex traditional Chinese medicine (TCM). This method makes separation of the components of the sample simple and structural elucidation easy. In this study, selective separation of alkaloids in Rhizoma coptidis was realized on a "click" binaphthyl column possessing a planar conjugate structure. Three kinds of alkaloids, aporphine, tetrahydroprotoberberine and protoberberine in Rhizoma coptidis showed better retention than other compounds by virtue of π-π interactions with the stationary phase. Moreover, the "click" binaphthyl column could distinguish the aporphine and tetrahydroprotoberberine alkaloids possessing two benzene rings from the protoberberine alkaloids possessing three benzene rings. After separating on the "click" binaphthyl column, the fractions containing the alkaloids were collected and then analyzed with liquid chromatography-mass spectrometry (LC-MS). Totally, 23 alkaloids were identified, and among these alkaloids, three tetrahydroprotoberberine, two aporphine and seven protoberberine alkaloids were first found in Rhizoma coptidis. These newly found alkaloids are minor compounds, and they are always neglected without eliminating the interference of compounds in large amounts by pre-separation on the "click" binaphthyl column. The typical fragmentation pathways of each class of alkaloids were summarized to illustrate their structures. In the MS(2) spectrum, the loss of a molecule of dimethylamine ((CH(3))(2)NH) was observed as the characteristic loss of aporphine alkaloids. All the tetrahydroprotoberberine alkaloids would undergo the Retro-Diels-Alder (RDA) fragmentation reaction in the MS(2) fragmentation. For protoberberine alkaloids, different characteristic fragmentations were observed with different skeleton structures.     

Characterization and identification of steroidal alkaloids in the Chinese herb Veratrum nigrum L. by high-performance liquid chromatography/electrospray ionization with multi-stage mass spectrometry

Electrospray ionization multi-stage mass spectrometry (ESI-MS(n)) was performed to study the fragmentation behaviour of seventeen steroidal alkaloids (4 protoverine-type alkaloids, 10 germine-type alkaloids and 3 zygadenin-type alkaloids) from the Chinese herb Veratrum nigrum L. The MS(n) spectra of the [M+H](+) ions for steroidal alkaloids provided a wealth of structural information on the substituted groups. In positive ion mode, the three types of alkaloids showed very different characteristic ions: m/z 436 or 418 for protoverine-type alkaloids; m/z 438, 420 or 402 for germine-type alkaloids; m/z 440 or 422 for zygadenin-type alkaloids. These fragments were used to deduce their mass spectral fragmentation mechanisms. Furthermore, the primary compounds in methanolic extracts of the herb of Veratrum nigrum L. were investigated by using liquid chromatography (LC)/ESI-MS(n). As a result, 21 steroidal alkaloids (5 protoverine-type alkaloids, 14 germine-type alkaloids and 2 zygadenin-type alkaloids) were selectively identified from 27 determined peaks. Eleven compounds were unambiguously identified by comparing with standard compounds and ten compounds were tentatively identified or deduced according to their MS(n) data. Two of these compounds (xingangermine and deacetyl xinganveratrine) were found to be novel steroidal alkaloids. In addition, the chemical structures of two pairs of steroidal alkaloid isomers were deduced by comparing their fragment ions. Given the important structural information of known and unknown steroidal alkaloids in crude herbal extracts, this study is useful for identifying these types of steroidal alkaloids in crude materials rapidly and selectively.     

Seven New Monoterpenoid Indole Alkaloids from Gelsemium elegans

Seven new indole alkaloids were isolated from the roots of Gelsemium elegans Benth. and their structures were determined by spectroscopic analysis and chemical transformation from known alkaloids. Kounaminal ( 1 ) is a new koumine‐type alkaloid that contains an unusual aminal moiety. Humantenoxenine ( 2 ) and 15‐hydroxyhumantenoxenine ( 3 ) are humantenine‐type alkaloids that contain a novel β‐amino‐α,β‐unsaturated ketone residue. The other four novel alkaloids are two gelsedilam‐related and two gelsenicine‐related alkaloids.     

New bisbenzylisoquinoline alkaloids from Cocculus laurifolius

Two new bisbenzylisoquinoline alkaloids, alpha, alpha'-dioxo-7'-O-demethylstebisimine (1) and 7'-O-demethylstebisimine (2), along with 14 known alkaloids, were isolated from the roots of Cocculus laurifolius. These alkaloids were characterized mainly by spectroscopic methods.     

Norditerpenoid alkaloids from the processed tubers of Aconitum carmichaeli

Four new and five known norditerpenoid alkaloids were isolated from the processed tubers of Aconitum carmichaeli. The new alkaloids are 14-O-cinnamoylneoline (3), 14-O-anisoylneoline (4) 14-O-veratroylneoline (5), and lipo-14-O-anisoylbikhaconine (8). The known alkaloids are neoline (1), 14-O-acetylneoline (2), foresaconitine (6), crassicauline A (7), and lipohypaconitine (9). Alkaloids 2, 6, and 7 were isolated from this plant for the first time. The structures of the new alkaloids were established by spectroscopic and chemical methods.     

Neuritogenic activity-guided isolation of a free base form manzamine A from a marine sponge, Acanthostrongylophora aff. ingens (Thiele, 1899)

Two manzamine-class alkaloids, manzamine A (1) and 8-hydroxymanzamine (2) were isolated from a Japanese marine sponge Acanthostrongylophora aff. ingens, together with three known alkaloids manzamine E (3), manzamine F (4), and manzamine X (5). The spectral features of 1 and 2 were different from the reported data. Detailed structure analysis using 2D NMR revealed the structure of 1 and 2 as a free base form of hydrochloric salt. These manzamine-class alkaloids showed neuritogenic activity against Neuro 2a cells.     

Alkaloids of Tabernaemontana eglandulosa

From the leaves and twigs of Tabernaemontana eglandulosa 22 alkaloids, of which 12 are new, have been isolated. Besides tacamine (pseudo-vincamine) 7 other alkaloids of this new class of indole alkaloids were identified. A further three alkaloids of the cleavamine type, namely the known ( + )20R-15, 20-dihydro-cleavamine and (-)20S-15, 20-dihydro-cleavamine and one new alkaloid, which was tentatively identified as 14S, 20R-velbanamine, two new alkaloids of the pseudo-aspidospermidine type, namely 20R-l,2-dehydro-pseudo-aspidospermidine and 20S-hydroxy-l,2-dehydro-pseudoaspidospermidine and an alkaloid of a novel iboga type were isolated. More common alkaloids isolated were coronaridine, 11-hydroxycoronaridine, voaphylline, tubotaiwine, ibogamine, norfluorocurarine and probably a mixture of 20R- and 20S-pseudo-vincadifformine. Only quantitative differences in the alkaloid content of the leaves, twigs and stembark were observed.     

New C19-diterpenoid alkaloids from Aconitum piepunense

Two new C(19)-diterpenoid alkaloids, piepunensine A (1) and 18-acetylcammaconine (2), have been isolated from the roots of Aconitum piepunense together with five known alkaloids pengshenine B (3), talatisamine (4), aconosine (5), yunaconitine (6), and talatizidine (7). The structures of the new alkaloids were established on the basis of spectral data (1D- and 2D-NMR, HR-MS).     

Alkaloids from Fruits of Daphniphyllum oldhamii

Seventeen Daphniphyllum alkaloids, including two new pentacyclic alkaloids, yuzuric acid ( 1 ) and daphnezomic acid ( 2 ), and 15 known ones, were isolated from the fruits of Daphniphyllum oldhamii. The structures and configuration of the two new alkaloids were determined on the basis of spectroscopic methods, especially 2D NMR techniques.     

Studies on the intestinal absorption of the alkaloids in the Gancaofuzi decoction in a Caco-2 cell culture system by UPLC–MS/MS analysis

In this study, the Caco-2 cell monolayer model was used to research the characteristic absorption and efflux of five diterpenoid alkaloids in Gancaofuzi decoction. An ultra performance liquid chromatography coupled with tandem mass spectrometry(UPLC–MS/MS) method was developed for the determination of the simulated intestinal transport of five diterpenoid alkaloids with reserpine as internal standard. The use of the apparent permeability coefficient(Papp) and efflux rate(Er) was instituted to evaluate the intestinal absorption of the alkaloids. Transport of the five alkaloids in Caco-2cell monolayer model was observed to better understand whether the intestinal absorption of alkaloids was influenced by the compatibility of four herbs in Gancaofuzi decoction. The results show that the Papp values of the five diterpenoid alkaloids were all more than 1 * 10~(-6)cm/s, confirming that the processes of permeability were valid. The flux of the alkaloids was time-dependent, and the intestinal absorption mechanism of the five alkaloids was mainly based on passive transport. The compatibility of Heishunpian, Baizhu, Guizhi and Gancao can reduce the intestinal absorption of alkaloids, especially the most toxic hypaconitine, and the attenuated effect of mixed herbal water extracts was better than that of different herbs' water extracts combination. The results prove that compatibility of four herbs in Gancaofuzi decoction is rational.     

Puberunine and puberudine, two new C18-diterpenoid alkaloids from Aconitum barbatum var. puberulum

Two C(18)-diterpenoid alkaloids, puberunine (1) and puberudine (2), together with four other new alkaloids, including the first examples having β-oriented substitution at C-3 and a rare chloro-substituent were isolated from Aconitum barbatum var. puberulum. Their structures were elucidated by spectroscopic methods. Puberunine and puberudine, which possess a unique rearranged E ring and an opened A ring, respectively, represent new subtypes of the C(18)-diterpenoid alkaloids. A plausible biosynthetic pathway of 1 and 2 was proposed.     

Two new alkaloids from Crinum asiaticum var. sinicum

Two new alkaloids (1, 2) were isolated from the whole plants of Crinum asiaticum var. sinicum together with seven known alkaloids. The structures of the new alkaloids were elucidated by spectroscopic analyses and chemical conversions from known alkaloids. New alkaloid 1 was isolated for the first time as a natural product, although it has been prepared as a synthetic product.     

云南蕊木茎中的抗炎吲哚生物碱

应用多种色谱和波谱学方法,从云南蕊木(Kopsia officinalis)茎中分离鉴定了27个单萜吲哚生物碱,包括7个新化合物kopsiofficines A～G和20个已知化合物.此外,建立脂多糖(LPS)诱导的小鼠巨噬细胞RAW 264.7炎症模型,通过测定IL-1β, PGE2和TNF-α炎症因子释放评价生物碱的抗炎活性.结果表明, kopsiofficines A (1), kopsiofficines B (2),kopsiofficines D(4),kopsiofficines F(6),kopsiofficines G(7), 12-methoxykopsine(11),kopsinoline(15),(-)-N-methoxy-carbonyl-11,12-methylenedioxykopsinaline(16),kopsinine(18)和kopsinic acid(20)表现出显著的抗炎活性,与阳性对照(地塞米松)基本相当.研究发现C-5位丙酮基取代的单萜吲哚生物碱的抗炎活性明显强于原型生物碱,推测丙酮基可能是抗炎活性的药效促进基团,研究结果为进一步的结构修饰...     

New bisindole alkaloids isolated from Myxomycetes Arcyria cinerea and Lycogala epidendrum

Two new bisindole alkaloids, named cinereapyrrole A (1) and B (2), were isolated from wild fruit bodies of Arcyria cinerea and three new bisindole alkaloids (3-5) were isolated from wild fruit bodies of Lycogala epidendrum. Seven known bisindoles (6-12) were concomitantly obtained from them. The structures of the new compounds were elucidated by spectral data. Among these bisindole alkaloids, compound 12 showed cytotoxicity against cultured tumor cell lines.     

New cholinesterase inhibiting bisbenzylisoquinoline alkaloids from Cocculus pendulus

Phytochemical investigation on Cocculus pendulus (J. R. & G. FORST.) resulted in the isolation of two new and three known bisbenzylisoquinoline alkaloids. The structures of the new alkaloids, kurramine-2'-beta-N-oxide (1) and kurramine-2'-alpha-N-oxide (2), were elucidated with the help of spectroscopic techniques. The cholinesterase inhibitory activities of these bisbenzylisoquinoline alkaloids are reported here for the first time.     

Three new sesquiterpene alkaloids from the root of Tripterygium wilfordii

<正>Three new sesquiterpene alkaloids,1-desacetylwilforgine(1),1-desacetylwilforine(2),and 9′-hydroxy-2-nicotinoylwilforine (3) were isolated from the roots of Tripterygium wilfordii Hook f.,along with six known alkaloids.Their structures were established on the basis of spectral analysis.     

华佗豆生物碱间的相互转化

我国广西省植物华佗豆Ipomoea hardwickii Hemsl(Convolvulaceae)在民间用来镇痛。从其中分离到甲、乙、戊、丁四种生物碱,其结构分别为1,2,3,4。     

Two New Indole Alkaloids from Emmenopterys henryi

Two new indole alkaloids, 5‐oxodolichantoside ( 1 ) and deglycocadambine ( 2 ), were isolated from the twigs and leaves of Emmenopterys henryi, together with four known indole alkaloids and five known iridoids. The structures of the new compounds were elucidated on the basis of extensive spectroscopic analyses, including 1D‐ and 2D‐NMR experiments, and confirmed by single‐crystal X‐ray diffraction studies. This is the first report on the isolation of indole alkaloids from this species. The indole alkaloids were evaluated for their cytotoxic activities against five human cancer lines.     

Studies of the intestinal absorption of the alkaloids in the Wu-tou decoction combined with different incompatible medicinal herbs in a Caco-2 cell culture system using UPLC-MS/MS

In this study, seven alkaloids were detected in Wu-tou decoction using ultra performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MSn). The aim of this study was to investigate the effect of Fritillariae Cirrhosae Bulbus, Fritillariae Thunbergii Bulbus, Pinelliae Rhizoma in different ratios with Wu-tou decoction (2:1, 1:1, 1:2) by measuring the therapeutic effects in Wu-tou decoction of main seven alkaloids including benzoylaconitine (BA), benzoylmesaconitine (BM), benzoylhypaconitine (BH), hypaconitine (HA), fuziline (FU), niaolin (NE) and deoxyaconitine (DA). The permeability of aconitum alkaloids extract through a Caco-2 cell monolayer was analyzed in the absence and presence of Fritillariae Cirrhosae Bulbus, Fritillariae Thunbergii Bulbus, and Pinelliae Rhizoma, respectively. The results showed that Pinelliae Rhizoma could reduce the absorption of the alkaloids and increase the excretion of the alkaloids, which would attenuate the therapeutic effects of Wu-tou decoction. Therefore, Pinelliae Rhizoma is an incompatible herb of Wu-tou decoction because of the inhibition of the absorption of alkaloids in the intestine. And that Fritillariae Cirrhosae Bulbus and Fritillariae Thunbergii Bulbus showed the effects to improve the permeability of the alkaloids in Wu-tou decoction. These effects of these two herbs were similar, but the former was stronger than the latter, which most likely is due to the fact that the compositions of these two traditional Chinese medicines are similar. The in vitro data suggests that the compounds such as fritillary presented in alkaloids in the formula maybe improve the therapeutic function caused by the increased bioavailability of alkaloids in intestine.     

弯距翠雀花中二萜生物碱的结构鉴定

从弯距翠雀花(Delphinium campylocentrum Maxim.)全草中分离得到7种二萜生物碱, 其中弯翠生(1)和弯翠亭(2)为两个新的C₁₉-二萜生物碱, 其余5个为已知的二萜生物碱. 化合物1和2的结构通过现代波谱技术, 包括二维核磁共振谱和高分辨质谱, 予以了确证.