知母中呋甾皂甙的研究

自知母 Anemarrhena asphodeloides Bge.根茎的乙醇提取物中,经硅胶柱层析和制备型HPLC分得四种呋甾皂甙。用化学反应和波谱(IR,FAB-MS,EI-MS,¹HNMR,¹³CNMR,DEPT,一维多重接力CoSY,二维接力HOHAHA,¹H-¹H COSY,¹H-¹³C COSY和NOE差谱)解析,确定其结构为知母皂贰B(anemarsaponinB,I),(25S)-26-O-β-D-吡喃葡萄糖基-5β-呋甾-20(22)-烯-3β,26-二醇-3-O-β-D-吡喃葡萄糖基(1→2)-β-D-吡喃哺葡萄糖甙(Ⅱ),(25S)-26-O-β-D-吡喃葡萄糖基-22-羟基-5β-呋甾-3β,26-二醉-3-O-β-D-吡喃葡萄糖基(1→2)-β-D-吡喃半乳糖甙(Ⅲ),(25S)-26-O-β-D-吡喃葡萄糖基-22-甲氧基-5β-呋甾-3β,26-二醇-3-O-β-D-吡喃葡萄糖基(1→2)-β-D-吡喃半乳糖甙(Ⅳ)。Ⅱ为一新的呋甾皂甙,命名为知母皂甙C;化合物Ⅳ为首次从知母中分离得到,命名为知母皂甙E。初步的药理实验显示,化合物1～Ⅳ均有一定的清除羟自由基的作用。     

商陆中三种新皂甙的分离与鉴定

从商陆科植物商陆(Phytolacca esculenta Van Houtte)中分离得三种新的三萜皂甙,根据化学性质和光谱分析(UV,IR,¹HNMR,¹³CNMR,MS),确定甙Ⅰ为3-O-β-D-吡喃木糖基商陆酸,甙Ⅱ为3-O-β-D-吡喃葡萄糖基-羟基商陆酸,甙Ⅲ为3-O-[β-D-吡喃葡萄糖基(1→4)-β-D-吡喃木糖基(1→4)-β-D-吡喃葡萄糖基]-2-羟基商陆酸,分别命名为商陆皂甙O,P,Q。     

知母皂甙E1和E2

应用硅胶柱色谱、高效液相色谱等分离手段,从中药知母(Anemarrhena asphodeloides Bge.)分离得到2种新的呋甾皂甙,经光谱(IR,ESI MS,¹HNMR,¹³HNMR)分析和化学反应,鉴定其结构分别是:(25S)-26-O-β-D-吡喃葡萄糖基-22-羟基-5-β-呋甾-3β,15α,26-三醇-3-O-β-D-吡喃葡萄糖基(1→2)-β-D-吡喃半乳糖甙(1),(25S)-26-O-β-D-吡喃葡萄糖基-22-甲氧基-5β-呋甾-3β,15α,26-三醇-3-O-β-D-吡喃葡萄糖基(1→2)-β-D-吡喃半乳糖甙(2)。(1)是新化合物,命名为知母皂甙E1;(2)是(1)的甲醚化人工产物,命名为知母皂甙E2。对知母皂甙-I(A)的结构分析作了简单说明。     

薤白中两种新呋甾皂甙的结构

自中药薤白(Allium macrostemon Bunge)鳞茎中分得三种甾体皂甙。经过化学降解和光谱(UV、IR,MS,¹H-NMR,¹³C-NMR和FAB-MS)分析,鉴定其结构分别为(25R)-26-O-β-D-吡喃葡萄糖-5α-呋甾-20(22)-烯-3β,26-二醇-3-O-β-D-吡喃葡萄糖基(1→2)[β-D-吡喃葡萄糖基(1→3)]-β-D-吡喃葡萄精基(1→4)-β-D-吡喃半乳糖甙(Ⅰ),(25R)-26-O-β-D-吡喃葡萄糖基-5β-呋甾-20(22)-烯-3β,26-二醇-3-P-β-D-吡喃葡萄糖基(1→2)-β-D-吡喃半乳糖甙(Ⅱ)和异菝契皂甙元-3-O-D-吡喃葡萄糖基(1→2)-β-D-吡喃半乳糖甙(Ⅵ)。Ⅰ和Ⅱ为新的呋甾皂甙,分别命名为薤白甙戊和莲白甙己,初步药理实验测试二青均有较强的抑制ADP诱导的人血小板聚集作用。     

川续断中的新三萜皂甙

从川续断(Dispsacus asper Wall.)根的乙醇提取物中得到二个新三萜皂甙(Ⅶ和Ⅷ)。根据光谱分析、化学反应及双向高效薄层层析结果,证明其结构分别为:3-O-β-D-吡喃葡萄糖(1→3)-α-L-吡喃鼠李糖(1→2)-α-L-吡喃阿拉伯糖常春藤皂甙元28-O-β-D-吡喃葡萄糖(1→6)-β-D-吡喃葡萄糖酯甙和3-O-α-L-吡喃鼠李糖(1→3)-β-D-吡喃葡萄糖(1→3)-α-L-吡喃鼠李糖(1→2)-α-L-吡喃阿拉伯糖-常春藤皂甙元28-O-β-D-吡喃葡萄糖(1→6)-β-D-吡喃葡萄糖酯甙。     

湖北山麦冬化学成分的研究

从湖北山麦冬(Liriope spicata Lout(Thunb).var.prolifera Y.T.Ma)块根的醇提物中分得四种甾体甙类化合物,根据化学性质和波谱(IR,¹HNMR,¹³CNMR,EI-MS,FAB-MR)分析,确定甙Ⅰ为以β-谷甾醇为主、豆甾醇为次的混合甾醇的β-D-吡喃葡萄糖甙;甙Ⅱ为25(S)-鲁斯可皂甙元1-O-β-D-吡喃夫糖3-O-α-L-吡喃鼠李糖甙;甙Ⅲ为25(S)-鲁斯可皂甙元1-O-α-L-吡喃鼠李糖基(1→2)-β-D-吡喃木糖甙;甙Ⅳ为25(S)-鲁斯可皂甙元1-O-[α-L-吡喃鼠李糖基(1→2)](β-D-吡喃木糖基(1→3)]-β-D-吡喃夫糖甙,其中甙Ⅲ和甙Ⅳ为新的甾体皂甙。     

川续断的化学成分研究

从川续断(Dosacus asper Wall)的根中分得六个化合物(Ⅰ～Ⅵ)。Ⅰ,Ⅱ,Ⅲ和Ⅵ分别鉴定为蔗糖、胡萝卜甙、β-谷甾醇和akebia saponin D.Ⅵ和Ⅴ为新化合物,根据光谱分析和化学方法证明其结构分别为3-O-(4-O-乙酰基)-α-L-吡喃阿拉伯糖常春藤皂甙元28-O-β-D-吡喃葡萄糖-(1→6)-β-D-吡喃葡萄糖酯甙和3-O-α-L-吡喃阿拉伯糖齐墩果酸28-O-β-D-吡喃葡萄糖-(1→6)-β-D-吡喃葡萄糖酯甙。     

薤白甙J,K和L的结构

进一步用HPLC自小根蒜(Allium macrostemon Bunge)鳞茎中分得两种新的呋甾皂甙,薤白甙J(1)和薤白甙L(III),以及I的甲基化人工产物薤白甙K(II)。经过化学降解和光谱(¹H-NMR,¹³C-NMR和FAB-MS等)分析,确定其结构分别为:(25R)-26-O-β-D-吡喃葡萄糖基-22-羟基-5β-呋甾-2β,3β,26-三醇-3-O-β-D-吡喃葡萄糖基(1→2)-β-D-吡喃半乳糖甙(I);(25R)-26-O-β-D-吡喃葡萄糖基-22-甲氧基-5β-呋甾-2β,3β,26-.三醇-3-O-β-D-吡喃葡萄糖基(1→2)-β-D-吡喃半乳糖甙(II)和(25R)-26-O-β-D-吡喃葡萄糖基-5β-呋甾-20(22)-烯-26β,3β,26-三醇-3-O-β-D-吡喃葡萄糖基(1→2)-β-D-吡喃半乳糖甙(III)。     

知母中的两种新呋甾皂苷

目的研究知母根茎的化学成分。方法采用水煎提取、大孔吸附树脂SP825柱色谱、反相C₁₈柱色谱等进行分离，并通过化学手段和光谱分析(FAB-MS，¹H NMR，13C NMR，¹H-¹H COSY)鉴定其化学结构。结果从知母根茎中分离得到6种甾体皂苷，分别鉴定为：(25S)-26-O-β-D-吡喃葡糖基-22-羟基-5β-呋甾-2β，3β，26-三醇-3-O-β-D-吡喃葡糖基-(1→2)-β-D-吡喃半乳糖苷(知母皂苷N，1)，知母皂苷E_l(2)，(25S)-26-O-β-D-吡喃葡糖基-22-甲氧基-5β-呋甾-2β，3β，26-三醇-3-O-β-D-吡喃葡糖基-(1→2)-β-D-吡喃半乳糖苷(知母皂苷O，3)，知母皂苷E₂(4)，(25R)-26-O-β-D-吡喃葡糖基-22-羟基-5α-呋甾-2α，3β，26-三醇-3-O-β-D-吡喃葡糖基-(1→2)-［β-D-吡喃木糖基-(1→3)］-β-D-吡喃葡糖基-(1→4)-β-D-吡喃半乳糖苷(purpureagitosid，5)，marcogenin-3-O-β-D-glucopyranosyl-(1→2)-β-D-galactopyranoside (6)。结论化合物1和3为新化合物，命名为知母皂苷N和知母皂苷O，化合物5为首次从知母中分离得到。     

知母的皂苷成分

目的：研究知母的化学成分,寻找新的活性物质。方法：利用大孔树脂柱色谱、硅胶柱色谱及高效液相色谱等手段进行分离,根据化合物的理化性质及光谱(IR,FAB-MS,ESI-MS,¹HNMR,¹³CNMR,DEPT,HMQC,HMBC,NOESY和ROESY)数据鉴定结构。结果：从中药知母分离得到两种甾体皂苷,确定其结构是：(5β,25S)-螺甾烷-3β,15α,23α-三醇-3-O-β-D-吡喃葡萄糖基(1→2)-β-D-吡喃半乳糖苷(1)和(5β,25S)-螺甾烷-3β,23α-二醇-3-O-β-D-吡喃葡萄糖基(1→2)-β-D-吡喃半乳糖苷(2)。结论：1和2均是新化合物,分别命名为知母皂苷F和知母皂苷G。     

A new active steroidal saponin from Anemarrhena asphodeloides.

A new active steroidal saponin, anemarsaponin B, was isolated from the rhizomes of Anemarrhina asphodeloides. The structure of anemarsaponin B was elucidated as 26-O-beta-D-glucopyranosylfurost-20(22)-ene-3 beta, 26-diol-3-O-beta-D-glucopyranosyl-(1----2)-beta-D-galactopyranoside by chemical and spectral studies. Preliminary pharmacological tests showed that anemarsaponin B could inhibit PAF-induced rabbit platelet aggregation in vitro.     

The pharmacokinetic study on the interaction between nobiletin and anemarsaponin BII in vivo and in vitro

ContextThe interaction between nobiletin and anemarsaponin BII could affect the pharmacological activity of these two drugs during their combination.ObjectiveThe co-administration of nobiletin and anemarsaponin BII was investigated to explore the interaction and the potential mechanism.Materials and methodsMale Sprague-Dawley rats were only orally administrated with 50 mg/kg nobiletin as the control and another six rats were pre-treated with 100 mg/kg anemarsaponin BII for 7 d followed by the administration of nobiletin. The transport and metabolic stability of nobiletin were evaluated in vitro, and the effect of anemarsaponin BII on the activity of CYP3A4 was also assessed to explore the potential mechanism underlying the interaction.ResultsThe increasing C_max (2309.67 ± 68.06 μg/L vs. 1767.67 ± 68.86 μg/L), AUC (28.84 ± 1.34 mg/L × h vs. 19.57 ± 2.76 mg/L × h), prolonged t_1/2 (9.80 ± 2.33 h vs. 6.24 ± 1.53 h), and decreased clearance rate (1.46 ± 0.26 vs. 2.42 ± 0.40) of nobilein was observed in rats. Anemarsaponin BII significantly enhanced the metabolic stability of nobiletin in rat liver microsomes (half-life increased from 31.56 min to 39.44 min) and suppressed the transport of nobiletin in Caco-2 cells (efflux rate decreased from 1.57 ± 0.04 to 1.30 ± 0.03). The inhibitory effect of anemarsaponin BII on CYP3A4 was also found with an IC₅₀ value of 10.23 μM.Discussion and conclusionsThe interaction between anemarsaponin BII and nobiletin was induced by the inhibition of CYP3A4, which should draw special attention in their clinical co-administration.     

UPLC-MS/MS法测定清肺抑火丸中4种有效成分的含量

目的：建立UPLC-MS/MS法同时测定清肺抑火丸中知母皂苷BⅡ/BⅢ、菝葜皂苷元和桔梗皂苷元的含量。方法：采用Waters ACQUITY UPLC BEH C₁₈（2.1 mm×100 mm,1.7 μm）色谱柱,以水-乙腈为流动相,流速为0.2 mL·min^-1,柱温为40℃,进样量为2 μL;采用电喷雾离子源在正、负模式下以多反应监测方式进行定量分析;通过样品测定值的分析比较,评价不同批次及不同企业样品间的质量差异。结果：4种成分均在检测范围内进样量与峰面积线性关系良好,方法精密度、稳定性、重复性和回收率均符合要求。比较测定结果发现各企业批间样品均一性较好,但不同企业间样品的测定结果差异显著,仅1家企业的样品符合限度要求。相关性分析结果显示样品中知母皂苷BⅡ/BⅢ的总量与菝葜皂苷元含量呈正相关。结论：该法简便快捷、重复性好、准确度高,可提升清肺抑火丸的质量控制水平。     

Three new steroidal saponins from Fritillaria pallidiflora

Three new steroidal saponins, pallidiflosides A (1), B (2), and C (3), have been isolated from the dry bulbs of Fritillaria pallidiflora Schrenk. Their structures were elucidated as 26-O-β-d-glucopyranosyl-(25R)-furost-5,20(22)-dien-3β,26-diol-3-O-β-d-xylopyranosyl(1?→?4)-[α-l-rhamnopyranosyl(1?→?2)]-β-d-glucopyranoside (1); 26-O-β-d-glucopyranosyl-3β,26-dihydroxyl-20,22-seco-25(R)-furost-5-en-20,22-dione-3-O-α-l-rhamnopyranosyl(1?→?2)-β-d-glucopyranoside (2); and (25R)-spirost-5-ene-3β,17α-diol-3-O-β-d-glucopyranosyl(1?→?4)-β-d-galactopyranoside (3) by spectroscopic techniques and chemical means.     

Furostanol oligoglycosides from Asparagus cochinchinensis

Three new furostanol oligoglycosides, named aspacochioside A (1), B (2) and C (3), together with the known compound 3-O-[(alpha-L-rhamnopyranosyl-(1 --> 4))(beta-D-glucopyranosyl)]-26-O[beta-D-glucopyranosyl]-(25S)-5beta-spirostane-3beta-ol were isolated from the roots of Asparagus cochinchinensis. Their structures were elucidated by spectroscopic techniques (IR, HR-ESIMS, ESIMS/MS, ID and 2D NMR) and chemical methods as 3-O-[(alpha-L-rhamnopyranosyl-(1 --> 4))(beta-D-glucopyranosyl)]-26-O-[beta-D-glucopyranosyl]-(25S)-5beta-furostane-3beta,22alpha,26-triol (1), 3-O-[(alpha-L-rhamnopyranosyl-(1 --> 4))(beta-D-glucopyranosyl)]-26-O-[beta-D-glucopyranosyl]-22alpha-methoxy-(25S)-5beta-furostane-3beta,26-diol (2), and 3-O-[(alpha-L-rhamnopyranosyl-(1 --> 4))(beta-D-glucopyranosyl)]-26-O-[beta-D-glucopyranosyl]-(25S)-5beta-furost-20(22)-en-3beta,26-diol (3).     

知母中三个新的呋甾皂苷

从中药知母（ＡｎｅｍａｒｒｈｅｎａａｓｐｈｏｄｅｌｏｉｄｅｓＢｇｅ．）中分离出三种新的呋甾皂苷，初步鉴定为（２５Ｓ）－２６－Ｏ－β－Ｄ－葡萄糖－５β－呋甾－２０（２２）－双键－３β，２６－二醇－３－Ｏ－β－Ｄ－葡萄糖基（１→２）〔β－Ｄ－葡萄糖基（１→３）〕－β－Ｄ－葡萄糖基（１→４）－β－Ｄ－半乳糖苷（１），（２５Ｓ）－２６－Ｏ－β－Ｄ－葡萄糖基－２２－羟基－５β－呋甾－３β，２６－二醇－３－Ｏ－β－Ｄ－葡萄糖基（１→２）〔β－Ｄ－葡萄糖基（１→３）〕－β－Ｄ－葡萄糖基（１→４）－β－Ｄ－半乳糖苷（２），（２５Ｓ）－２６－Ｏ－β－Ｄ－葡萄糖基－２２－甲氧基－５β－呋甾－３β，２６－二醇－３－Ｏ－β－Ｄ－葡萄糖基（１→２）〔β－Ｄ－葡萄糖基（１→３）〕－β－Ｄ－葡萄糖基（１→４）－β－Ｄ－半乳糖苷（３）．分别命名为ｔｉｍｏｓａｐｏｎｉｎ－ＢⅣ，ｔｉｍｏ－ｓａｐｏｎｉｎ－ＢⅤ，ｔｉｍｏｓａｐｏｎｉｎ－ＢⅥ．     

Terrestrinins A and B, two new steroid saponins from Tribulus terrestris

Two new steroid saponins, named terrestrinins A (1) and B (2), along with six known compounds were isolated from the Chinese medicine herb Tribulus terrestris, and their chemical structures were elucidated as 26-O-beta-D-glucopyranosyl-(25S)-furostan-4(5),20(22)-diene-3,12-dione (1) and 26-O-beta-D-glucopyranosyl-(25S)-5alpha-furostane-3beta,22alpha,26-triol-3-O-beta-D-xylopyranosyl(1 --> 3)-[(beta-D-xylopyranosyl(1 --> 2)]-beta-D-glucopyranosyl(1 --> 4)-[alpha-L-rhamnopyranosyl(1 --> 2)]-beta-D-galactopyranoside (2) on the basis of spectroscopic techniques.     

Novel 1,3-dipropyl-8-(3-benzimidazol-2-yl-methoxy-1-methylpyrazol-5-yl)xanthines as potent and selective A₂B adenosine receptor antagonists

Molecular modeling studies, including the comparative molecular field analysis (CoMFA) method, on 52 antagonists of the A(2B) adenosine receptor with known biological activity were performed to identify the three-dimensional features responsible for A(2B) adenosine receptor antagonist activity. On the basis of these and previous results on the potent antagonist effect of 8-pyrazolyl-xanthines at human A(2B)AR, a new series of compounds was synthesized and evaluated in binding studies against the human A(1), A(2A), A(3), and A(2B)ARs. A remarkable improvement in selectivity with respect to the previous series, maintaining the potency at human A(2B) receptor, was achieved, as exemplified by the 8-[3-(4-chloro-6-trifluoromethyl-1H-benzoimidazol-2-yl-methoxy)-1-methyl-1H-pyrazol-5-yl]-1,3-dipropyl-3,7-dihydro-purine-2,6-dione derivative 66: K(i) A(2B) = 9.4 nM, IC(50) hA(2B) = 26 nM hA(1)/hA(2B) = 269, hA(2A)/hA(2B) > 106, hA(3)/hA(2B) >106. This study also led to the identification of a series of pyrazole-xanthine compounds with a simplified structure, exemplified by 8-(3-hydroxy-1-methyl-1H-pyrazol-5-yl)-xanthine 80 displaying very high affinity at A(2B)AR with good selectivity over AR subtypes (K(i) = 4.0 nM, IC(50) hA(2B) = 20 nM hA(1)/hA(2B) = 183, hA(2A),hA(3)/hA(2B) > 250).