New bioactive steroidal alkaloids from Buxus hyrcana

Phytochemical studies on the crude methanolic extract of Buxus hyrcana, collected from Iran, resulted in the isolation of two new steroidal alkaloids, (+)-O6-buxafurandiene (1) and (+)-7-deoxy-O6-buxafurandiene (2) along with four known steroidal bases, (+)-benzoylbuxidienine (3), (+)-buxapapillinine (4), (+)-buxaquamarine (5) and (+)-irehine (6). The structures of these new and known compounds were established with the aid of extensive NMR spectroscopic studies. Compounds 1 and 2 belong to the rarely occurring class of Buxus alkaloids having a tetrahydrofuran ring incorporated in their structures. Compounds 1-6 exhibited acetylcholinesterase enzyme inhibitory activity.     

卵叶娃儿藤中的抗癌活性生物碱

从卵叶娃儿藤 (Tylophoraovata (Lindl.)Hook .exSteud .)根中分离得到 4个菲骈吲哚里西丁类生物碱 ,分别为tylophoridicineA (1)、娃儿藤宁 (2 )、氧甲基娃儿藤定 (3)和娃儿藤定 (4 )。经波谱分析并结合化学方法鉴定 ,其结构分别为 :(13aR)_6_羟基_3,7_二甲氧基菲骈吲哚里西丁、(13aS ,14R)_14_羟基_3,6 ,7_三甲氧基_菲骈吲哚里西丁、(13aS ,14S)_14_羟基_3,6 ,7_三甲氧基_菲骈吲哚里西丁和 (13aS ,14S)_6 ,14_二羟基_3,7_二甲氧基_菲骈吲哚里西丁。化合物 1为新化合物 ,化合物 2 - 4为首次从该植物得到的化合物。经药理筛选 ,化合物 1、3和 4显示很强的抗癌活性。     

Two tetrahydroisoquinoline alkaloids from the fruit of Averrhoa carambola

The fruit of Averrhoa carambola, commonly known as star fruit or carambola, is popular in Southeast Asia and China. Two new tetrahydroisoquinoline alkaloids, (1R*,3S*)-1-(5-hydroxymethylfuran-2-yl)-3-carboxy-6-hydroxy-8-methoxyl-1,2,3,4-tetrahydroisoquinoline (1) and (1S*,3S*)-1-methyl-3-carboxy-6-hydroxy-8-methyoxyl-1,2,3,4-tetrahydroisoquinoline (2), were isolated from the fruit, along with vanillic acid (3), ferulic acid (4), 8,9,10-trihydroxythymol (5), and arjunolic acid (6). Their structures were elucidated by spectroscopic method. Compounds 1, 2, and 5 showed weak ferric reducing antioxidant potency (FRAP) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity.     

卵叶娃儿藤中的抗癌活性生物碱

从卵叶娃儿藤(Tylophora ovata (Lindl.) Hook. ex Steud.)根中分离得到 4个菲骈吲哚里西丁类生物碱,分别为tylophoridicine A (1)、娃儿藤宁(2)、氧甲基娃儿藤定(3)和娃儿藤定(4).经波谱分析并结合化学方法鉴定,其结构分别为:(13aR)-6-羟基-3,7-二甲氧基菲骈吲哚里西丁、 (13aS ,14R)-14-羟基-3,6,7-三甲氧基-菲骈吲哚里西丁、(13aS, 14S)-14-羟基-3,6,7-三甲氧基-菲骈吲哚里西丁和(13 aS,14S)-6,14-二羟基-3,7-二甲氧基-菲骈吲哚里西丁.化合物1为新化合物,化合物2-4为首次从该植物得到的化合物.经药理筛选,化合物1、3和4显示很强的抗癌活性.     

Anti-HIV benzylisoquinoline alkaloids and flavonoids from the leaves of Nelumbo nucifera, and structure-activity correlations with related alkaloids

(+)-1(R)-Coclaurine (1) and (-)-1(S)-norcoclaurine (3), together with quercetin 3-O-beta-D-glucuronide (4), were isolated from the leaves of Nelumbo nucifera (Nymphaceae), and identified as anti-HIV principles. Compounds 1 and 3 demonstrated potent anti-HIV activity with EC50 values of 0.8 and <0.8 microg/mL, respectively, and therapeutic index (TI) values of >125 and >25, respectively. Compound 4 was less potent (EC50 2 microg/mL). In a structure-activity relationship study, other benzylisoquinoline, aporphine, and bisbenzylisoquinoline alkaloids, including liensinine (14), negferine (15), and isoliensinine (16), which were previously isolated from the leaves and embryo of Nelumbo nucifera, were evaluated for anti-HIV activity. Compounds 14-16 showed potent anti-HIV activities with EC50 values of <0.8 microg/mL and TI values of >9.9, >8.6, and >6.5, respectively. Nuciferine (12), an aporphine alkaloid, had an EC50 value of 0.8 microg/mL and TI of 36. In addition, synthetic coclaurine analogs were also evaluated. Compounds 1, 3, 12, and 14-16 can serve as new leads for further development of anti-AIDS agents.     

New diterpenoid alkaloids from Aconitum heterophyllum Wall: Selective butyrylcholinestrase inhibitors

Two new diterpenoid alkaloids, heterophyllinine-A (1) and heterophyllinine-B (2), along with two known alkaloids dihydroatisine (3) and lycoctonine (4) were isolated from the roots of Aconitum heterophyllum Wall. The structure of (1) and (2), were deduced on the basis of spectral data. Compounds 1-2 inhibited acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BChE, EC 3.1.1.8) enzymes in a concentration-dependent manner with percent inhibition ranging between 4.24% and 6.94 % and 79.1 % and 82.75 % for AChE and BChE, respectively indicating that compounds 1 and 2 are about thirteen times more specific to BChE than AChE.     

Biosynthesis of slaframine, (1S,6S,8aS)-1-acetoxy-6-aminooctahydroindolizine, a parasympathomimetic alkaloid of fungal origin. 3. Origin of the pyrrolidine ring.

The phytopathogen Rhizoctonia leguminicola has previously been shown to incorporate pipecolic acid into the piperidine alkaloids 1-acetoxy-6-aminooctahydroindolizine (slaframine) and 3,4,5-trihydroxyoctahydro-1-pyrindine. In the experiments described here, resting cultures of R. leguminicola were incubated with [1-14C]- and [2-14C]malonic acid and with [1-14C]- and [2-2H]acetic acid. Both acids were incorporated into the ring systems of both alkaloids. Mass spectrometric analysis of 2H-enriched slaframine showed that the label resides in the five-membered ring and that the methyl carbon of acetate is joined to the carboxyl carbon of pipecolate. A pipecolate-dependent decarboxylation of [1-14C]malonate was demonstrated in cell-free extracts of R. leguminicola. The results account for previously unattributed carbons in the two alkaloids and suggest the formation of an eight-carbon intermediate common to both alkaloids by acylation of malonate with pipecolic acid.     

大花地不容块根生物碱成分的研究

为研究大花地不容块根的生物碱成分,该研究采用酸提碱沉法从大花地不容块根中提取出总生物碱,通过硅胶柱色谱法和制备液相色谱技术对大花地不容块根的总生物碱提取物进行分离纯化,并利用波谱学手段对化合物进行结构鉴定。结果表明:(1)从总生物碱提取物中分离得到11个化合物,分别鉴定为青藤碱(1)、青风藤碱(2)、斯帝酚灵碱(3)、瑞枯灵(4)、异紫堇定(5)、紫堇单酚碱(6)、巴婆碱(7)、sukhodianine(8)、荷包牡丹碱(9)、7-氧代克班宁(10)和巴马汀(11)。(2)体外细胞毒性测试显示,大花地不容总生物碱和其主成分青藤碱对人类肺癌细胞A549的IC₅₀值分别为7.5×10^-4 g·mL^-1和6.59×10^-9 g·mL^-1。化合物2、3、4、7、8、9和10系首次从大花地不容中分离得到。大花地不容块根中含有吗啡烷、原阿朴啡、阿朴啡、苄基四氢异喹啉和原小檗碱5种类型的生物碱。     

New class of steroidal alkaloids from Fritillaria imperialis

Two members of a new class of C-nor-D-homo steroidal alkaloids, impranine (1). and dihydroimpranine (2). along with a new pyridyl-pregnane-type steroidal alkaloid, fetisinine (3). and a known base, korsevine (4). were isolated from the bulbs of Fritillaria imperialis. The structures of the compounds were established on the basis of spectroscopic techniques and some chemical transformations. Compounds 1 and 2 form a new class of steroidal alkaloids, named as "impranane."     

Lupin alkaloids from flowers of Echinosophora koreensis

(?)-Methyl 12-cytisineacetate (2) was isolated from methanol extracts of fresh flowers of Echinosophora koreensis together with seven known lupin alkaloids. Ethyl 12-cytisineacetate (3) was also isolated from ethanol extracts of the same flowers. Compounds 2 and 3 were artifacts and (?)-12-cytisineacetic acid (4) is assumed to be the principal source of 2 and 3. The variations in alkaloid content during growth of the flowers and the seedlings were also examined.     

Alkaloids from Corydalis saxicola and their anti-hepatitis B virus activity

Eight protoberberine-type alkaloids and two indole alkaloids were isolated from the MeOH extracts of the herb Corydalis saxicola Bunting (Papaveraceae). Their structures were identified as dehydrocavidine (1), dehydroapocavidine (2), dehydroisoapocavidine (3), berberine (4), dehydroisocorypalmine (5), coptisine (6), tetradehydroscoulerine (7), berbinium (8), 1-formyl-5-methoxy-6-methylindoline (9), and 1-formyl-2-hydroxy-5-methoxy-6-methylindoline (10). Compounds 3, 9, and 10 are new alkaloids. All compounds were tested for anti-HBV activity against the 2.2.15 cell line in vitro. Dehydrocavidine (1), dehydroapocavidine (2), and dehydroisoapocavidine (3) exhibited inhibitory activity against HBsAg and HBeAg, but no cytotoxicity against the 2.2.15 cell line.     

SC-41930 inhibits neutrophil infiltration of the cavine dermis induced by 12(R)-hydroxyeicosatetraenoic acid

Psoriasis is a disease state characterized by epidermal proliferation, neutrophil infiltration, along with release of the proinflammatory mediators leukotriene-B4 (LTB4) and 12(R)-hydroxyeicosatetraenoic acid [12(R)-HETE]. LTB4 and 12(R)-HETE are chemoattractant to the neutrophil, the latter approximately 1000X less potent. LTB4 and 12(R)-HETE are present in psoriatic scale, the latter in quantities so much greater than LTB4 that it is proposed as a primary mediator of neutrophil infiltration in psoriasis. 12(R)-HETE, synthesized in optically pure form by a new, shorter route, was injected into the cavine dermis. At a dose of 25 micrograms m per intradermal site, 12(R)-HETE was a significant chemoattractant to the neutrophil (as assessed by dermal myeloperoxidase levels). SC-41930, 7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-propoxy]- 3,4-dihydro-8-propyl-2H-1-benzopyran-2-carboxylic acid, given intragastrically inhibited 12(R)-HETE-induced neutrophil infiltration of the cavine dermis with an ED50 value of 13.5 mg/kg. Compounds such as SC-41930 may well have utility for treating human psoriasis.     

Alkaloids from Heimia salicifolia

Two alkaloids, 9β,2′-dihydroxy-4′′,5′′-dimethoxy-lythran-12-one or 9β-hydroxyvertine (1) and (2S,4S,10R)-4-(3-hydroxy-4-methoxyphenyl)-quinolizidin-2-acetate (2), as well as seven known alkaloids, lythrine (3), dehydrodecodine (4), lythridine (5), vertine (6), heimidine (7), lyfoline (8) and epi-lyfoline (9), were isolated from Heimia salicifolia. The structures of these compounds were elucidated by extensive spectroscopic techniques. Furthermore, the structures of 2, 3, and 6 were confirmed by X-ray crystallography, including absolute configuration determination of 2 and 6. Compounds 6 and 9 showed moderate antimalarial activity.     

Isolation and enzyme-inhibition studies of the chemical constituents from Ajuga bracteosa

Bractin A (=(2S,3S,4R,5E)-2-{[(2R)-2-hydroxydodecanoyl]amino}triacont-5-ene-1,3,4-triol; 1) and bractin B (=(2S,3S,4R,5E,8E)-2-{[(2R)-2-hydroxyhexacosanoyl]amino}pentadeca-5,8-diene-3,4,15-triol 1-O-beta-D-glucopyranoside; 2), new sphingolipids, and bractic acid (=(5Z,10Z,15Z)-2-decyl-4,7,8,12,13,17,18-heptahydroxy-20,23-dioxopentacosa-5,10,15-trienoic acid; 3), a long-chain polyhydroxy acid, were isolated from the whole plant Ajuga bracteosa along with four known diterpenoids 4-7. Their structures were deduced by spectral studies including 1D- and 2D-NMR spectroscopy. Compounds 1-3 displayed inhibitory potential against enzyme lipoxygenase, while compounds 4-7 inhibited cholinesterase enzymes in a concentration-dependent manner with IC(50) values in the range 10.0-33.0, 14.0-35.2, and 10.0-19.0 microM for lipoxygenase, acetylcholinesterase, and butyrylcholinesterase, respectively. Lineweaver-Burk, and Dixon plots, and their secondary replots indicated that all compounds exhibit non-competitive type of inhibition with K(i) values in the range of 9.5-35.2, 15.2-36.0, and 11.6-20.5 microM, for lipoxygenase, acetylcholinesterase, and butyrylcholinesterase, respectively.     

马兰化学成分研究 （Ⅱ）

采用冷渗漉提取的方法提取马兰的化学成分。经硅胶柱色谱和Sephadex LH-20进行分离纯化,通过理化方法和波谱数据分析进行结构鉴定。从80%乙醇冷渗漉提取物的水不溶物中分离并鉴定了12个化合物,分别为正十六烷酸(1)、6-羟基-桉烷-4(14)-烯(2)、β-谷甾醇(3)、α-菠菜甾醇(4)、香草醛(5)、β-20(21),24-二烯-达玛烷-3-酮(6)、豆甾醇(7)、木栓酮(8)、羽扇豆酮(9)、α-香树脂醇(10)、表木栓醇(11)、神经酰胺(12)。化合物2、6、9、12均为首次从该种植物中分得。     

Tetrahydroisoquinoline alkaloids of the Mexican columnar cactus Pachycereus Weberi

Eight tetrahydroisoquinoline alkaloids have been crystallized and identified from the nonphenolic and phenolic extracts of the giant Mexican cereoid cactus, Pachycereus weberi (Coult.) Br. and R. The identities were established as 5,6,7-trimethoxy-1,2,3,4- tetrahydroisoquinoline (nortehuanine) 1; 7,8-dimethoxy-1,2,3,4-tetrahydroisoquinoline (lemaireocercine) 2; 7-methoxy-1, 2,3,4-tetrahydroisoquinoline (weberidine) 3; 5,6,7,8-tetramethoxy-1,2,3,4-tetrahydroisoquinoline (weberine) 4; 6,7- dimethoxy-1,2,3,4-tetrahydroisoquinoline (heliamine) 5; 2-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (N- methylheliamine or oxymethyl-corypalline) 6; 2-methyl-5,6,7-trimethoxy-1,2,3,4-tetrahydroisoquinoline (tehuanine) 7; and 1,2-dimethyl-6,7-dimethoxy-8-hydroxy-1,2,3,4-tetrahydroisoquinoline (pellotine) 8. Compounds 1- 4 have not been identified previously as natural compounds, while compounds 5-8 are previously known cactus alkaloids.     

Isolation, characterization and antiplasmodial activity of steroidal alkaloids from Funtumia elastica (Preuss) Stapf

Bioassay-guided fractionation of the EtOH extract of the stem bark of Funtumia elastica resulted in the isolation of four steroidal alkaloids, holarrhetine (1), conessine (2), holarrhesine (3) and isoconessimine (4). Their structures were determined on the basis of 1D- and 2D-NMR techniques and mass spectrometry. Compounds 1-4 exhibited in vitro antiplasmodial activity against the chloroquine-resistant strain FcB1 of Plasmodium falciparum with IC50 values ranging from 0.97 to 3.39 microM. They showed weak cytotoxicity against a rat cell line L-6 with IC50 values ranging from 5.13 to 36.55 microM.     

Cholinesterase-inhibiting withanolides from Ajuga bracteosa

Three new withanolides, bracteosin A (= (22R)-5beta,6beta : 22,26-diepoxy-4beta,28-dihydroxy-3beta-methoxyergost-24-ene-1,26-dione; 1), bracteosin B (= (22R)-5beta,6beta : 22,26-diepoxy-4beta,28-dihydroxy-3beta-methoxy-1,26-dioxoergost-24-en-19-oic acid; 2), and bracteosin C (= (22R)-22,26-epoxy-4beta,6beta,27-trihydroxy-3beta-methoxyergost-24-ene-1,26-dione; 3), have been isolated from the whole plants of Ajuga bracteosa. Their structures were deduced by spectral analysis, including 1D- and 2D-NMR techniques. In addition, dihydroclerodin-1, clerodinin A, lupulin A, and dihydroajugapitin have also been isolated for the first time from this species. Compounds 1-3 exhibited evident inhibitory potential against cholinesterase enzymes in a concentration-dependent fashion.     

Potential anti-allergic acridone alkaloids from the roots of Atalantia monophylla

Acridone alkaloids, cycloatalaphylline-A (1), N-methylcyclo-atalaphylline-A (2) and N-methylbuxifoliadine-E (3), were isolated from the dichloromethane and acetone extracts of the root of Atalantia monophylla along with eight known acridone alkaloids: buxifoliadine-A (4), buxifoliadine-E (5), N-methylatalaphylline (6), atalaphylline (7), citrusinine-I (8), N-methylataphyllinine (9), yukocitrine (10) and junosine (11) and two known coumarins: auraptene (12) and 7-O-geranylscopoletin (13). Their structures were elucidated on the basis of spectroscopic analyses. Compounds 2, 5 and 8 possessed appreciable anti-allergic activity in RBL-2H3 cells model with IC(50) values of 40.1, 6.1 and 18.7 microM, respectively.     

Alkaloids from the roots of Zanthoxylum nitidum and their antiviral and antifungal effects

Five alkaloids, 5,6-dihydro-6-methoxynitidine (1), dictamnine (2), gamma-fagarine (3), skimmianine (4), and 5-methoxydictamnine (5), were isolated from the roots of Zanthoxylum nitidum. Their structures and configurations were elucidated by spectroscopic methods and X-ray analysis. Compounds 1, 4, and 5 showed in vitro antiviral effect against hepatitis B virus, and compounds 2, 3, and 5 demonstrated marked antimitotic and antifungal activity.