胡椒属植物生物碱及木脂素类化合物研究新进展

目的 介绍近5年胡椒属植物化学成分及药理作用的研究进展。方法 查阅国内外资料并进行汇总、综述。结果 胡椒属植物的化学成分有生物碱、木脂素、苯丙素类、黄酮、挥发油等，药理研究表明该属植物具有镇痛、抗炎、抗微生物及拮抗血小板活化因子（PAF）等多方面活性。结论 这两类化合物是胡椒属植物主要的活性成分，应深入研究，从中发现具有活性的先导化合物。     

从小蓟中提取止血药成分咖啡酸

小蓟俗称刺蓟草或青刺蓟,花紫红色,味微苦,为菊科植物刺儿菜的上干茎部分.盛产于甘肃、陕西、青海等地.小蓟入药始见于<名医别录>,考古代本草,小蓟以根入药,由于药物历史之变迁,目前均采用全草,称小蓟草,很少以根单独入药.根与全草功效相似,然全草药效偏于凉血止血,而根偏于化瘀消肿止血.小蓟性寒,入肝、脾经,以色绿叶多,又无杂质为佳.用于衄血、吐血、尿血、便血、崩漏下血、外伤出血和痈肿疮毒[1].因有凉血止血和祛疾利尿功能,还用于治疗各种出血热症、湿热黄疸、肾炎.利尿退黄,消肿,尤其对治疗血淋、血尿效果极佳.煎汤内服,外用以鲜品汁更佳.咖啡酸是小蓟有止血疗效的有效成分,属有机酸,具有缩短血凝及出血时间的作用,并可代替凝血酶作血浆纤维蛋白质平板法纤溶实验[2].因此,从小蓟中提取咖啡酸具有实际意义.     

Benzoic acid derivatives from Piper species and their antiparasitic activity

Piper glabratum and P. acutifolium were analyzed for their content of main secondary constituents, affording nine new benzoic acid derivatives (1, 2, 4, 5, 7, and 10-13), in addition to four known compounds (3, 6, 8, and 9). Their structures were elucidated on the basis of spectroscopic data. Riguera ester reactions and optical rotation measurements established the new compounds as racemates. In the search for antiparasitic agents, the compounds were evaluated in vitro against the promastigote forms of Leishmania spp., Trypanosoma cruzi, and Plasmodium falciparum. Among the evaluated compounds, methyl 3,4-dihydroxy-5-(3'-methyl-2'-butenyl)benzoate (7) exhibited leishmanicidal effect (IC50 13.8-18.5 microg/mL) against the three Leishmania strains used, and methyl 3,4-dihydroxy-5-(2-hydroxy-3-methylbutenyl)benzoate (1), methyl 4-hydroxy-3-(2-hydroxy-3-methyl-3-butenyl)benzoate (3), and methyl 3,4-dihydroxy-5-(3-methyl-2-butenyl) benzoate (7) showed significant trypanocidal activity, with IC50 values of 16.4, 15.6, and 18.5 microg/mL, respectively.     

Antifungal amides from Piper scutifolium and Piper hoffmanseggianum

Chromatographic fractionation of a dichloromethane extract from the leaves of Piper scutifolium yielded two new isobutyl amides, scutifoliamide A ( 1) and scutifoliamide B ( 2), together with the known compounds piperolactam C ( 3), piperovatine ( 4), piperlonguminine ( 5), corcovadine ( 6), isopiperlonguminine ( 7), and isocorcovadine ( 8). From the dichloromethane extract from the leaves of P. hoffmannseggianum two new isobutyl amides, hoffmannseggiamide A ( 9) and hoffmannseggiamide B ( 10), were obtained together with the known compounds isopiperlonguminine ( 7) and isocorcovadine ( 8), sitosterol, and stigmasterol. The structures of the new compounds were established on the basis of spectroscopic data analysis. The inhibitory activity of compounds 1-10 against the growth of the fungi Cladosporium sphaerospermum and C. cladosporioides was determined by bioautography.     

Antifungal activity of benzoic acid derivatives from Piper lanceaefolium.

Bioactivity-guided fractionation of a methanol extract from the leaves of Piper lanceaefolium resulted in the isolation of four new benzoic acid derivatives (1-4), together with taboganic acid, pinocembrin, and pinocembrin chalcone. Lanceaefolic acid methyl ester (3) and pinocembrin chalcone displayed activity against Candida albicans with a minimal inhibitory concentration value of 100 microg/mL in both cases.     

Synthesis of arieianal, a prenylated benzoic acid from Piper arieianum

Arieianal (1) is a complex prenylated benzoic acid that was isolated from Piper arieianum. It has been synthesized through a convergent sequence that joins a functionalized diterpenoid chain to a protected aromatic core. Key steps include use of a copper enolate for selective displacement of an allylic bromide in the presence of an allylic acetate and a stereoselective Horner-Wadsworth-Emmons condensation to afford the desired E olefin of the isoprenoid side chain. After the diterpenoid chain was joined to the aromatic ring, use of sodium metal in hot sBuOH allowed selective cleavage of two benzyl ether protecting groups, and a sequence of oxidations gave the target compound. This synthesis confirms the structure assigned to the natural product and establishes a route that may be used to prepare more active analogues.     

HPLC法测定蒲地蓝消炎胶囊中绿原酸和咖啡酸的含量

目的:建立高效液相色谱(HPLC)测定蒲蓝消炎胶囊中绿原酸和咖啡酸的含量.方法:色谱柱为C18(5μm,250 min×4.6 mm);流动相为甲醇-0.2%磷酸(用NaOH调节pH至2.8)(18:82);检测波长 323 nm:柱温:25℃,流速:1.0 mL·min-1.结果:绿原酸进样量在0.0975-0.585 μg范围内与峰面积线性关系良好,r=0.9999,平均回收率为98.8%,RSD%=0.36%;咖啡酸进样量在0.00625-0.0375 ug范围内与峰面积线性关系良好,r=0.9999平均回收率为98.7%,RSD%=0.46%,(n=6).结论:该方法简便,准确,重现性好.     

Collagenase inhibitory quinic acid esters from Ipomoea pes-caprae

Two new quinic acid esters (1 and 2) were isolated from the extract of Ipomoea pes-caprae together with six known quinic acid esters (3-8). The structures of compounds 1 and 2 were elucidated by spectroscopic data interpretation. These new compounds exhibited collagenase inhibitory activity and showed almost no cytotoxicity.     

Bioactive lignans from Peperomia heyneana

Four new compounds, including three secolignans (1-3) and one tetrahydrofuran lignan (4), were isolated from the petroleum ether and EtOAc fractions of Peperomia heyneana. These compounds were accompanied by eight known secolignans, one known tetrahydrofuran lignan, one known cyclohexenone, and one known amide. The structures were elucidated mainly by 1D and 2D NMR and MS experiments, and the relative configurations by NOE techniques. Five compounds were evaluated for their inhibitory activities against HIV-1 in infected C8166 cells.     

Furanoid lignans from Larrea tridentata

From the leaves and stems of Larrea tridentata six new furanoid lignans, compounds 1-6, have been isolated and their structures determined through interpretation of physical and spectroscopic properties. The use of 1D and 2D nOe experiments was of particular importance in assigning the stereochemistry.     

Four lignans from Commiphora erlangeriana

Four new lignans, two of the polygamatin-type, named erlangerin A (1) and erlangerin B (2), and two related to podophyllotoxin, named erlangerin C (3) and erlangerin D (4), were isolated from the resin of Commiphora erlangeriana, a plant occurring in Ethiopia and Somalia. The structures of these compounds including their relative stereochemistry were elucidated on the basis of spectral evidence, chemical data, and X-ray crystallographic analysis.     

Bioactive lignans from Peperomia duclouxii

Six new lignans (1-6), along with 14 known compounds, were obtained from Peperomia duclouxii. The new structures were elucidated mainly by the analysis of their NMR and MS data. The absolute configurations of 1-6 were determined by comparing their optical rotations or CD spectra with those of known compounds. In cytotoxic and MDR reversal cell activity assays, compound 3 showed cancer cell growth inhibitory activity against VA-13 and HepG2 cells, with IC50 values of 5.3 and 13.2 microg/mL, and more potent effects on calcein accumulation in MDR 2780AD cells than verapamil, a positive control. Compound 6 showed anti-inflammatory activity using an ICAM-1 assay (induction of the intercellular adhesion molecule-1), stimulated by IL-1alpha and TNF-alpha.     

Dibenzylbutyrolactone and dibenzylbutanediol lignans from Peperomia duclouxii

Nine new lignans (1-9), including five dibenzylbutyrolactones and four dibenzylbutanediols, were obtained from an ethyl acetate extract of the whole plants of Peperomia duclouxii. The structures of 1-9 were determined by spectroscopic methods (mainly extensive 1D and 2D NMR experiments and by mass spectral measurements). The absolute structures were elucidated as 2S,3S from their optical rotations and by chemical transformations.     

Antimycobacterial compounds from Piper sanctum

Bioassay-guided chromatographic separation of the antimycobacterial extract of the leaves of Piper sanctum afforded 14 new compounds, identified as 2-oxo-12-(3',4'-methylenedioxyphenyl)dodecane (1), 2-oxo-14-(3',4'-methylenedioxyphenyl)tetradecane (2), 2-oxo-16-(3',4'-methylenedioxyphenyl)hexadecane (3), 2-oxo-18-(3',4'-methylenedioxyphenyl)octadecane (4), 2-oxo-14-(3',4'-methylenedioxyphenyl)-trans-13-tetradecene (5), 2-oxo-16-(3',4'-methylenedioxyphenyl)-trans-15-hexadecene (6), 2-oxo-18-(3',4'-methylenedioxyphenyl)-trans-17-octadecene (7), 2-oxo-16-phenyl-trans-3-hexadecene (8), methyl [6-(10-phenyldecanyl)tetrahydropyran-2-yl]acetate (9), methyl 2-(6-tridecyltetrahydro-2H-pyran-2-yl)acetate (10), methyl 2-(5-tetradecyltetrahydro-2-furanyl)acetate (11), 2-oxo-14-(3',4'-methylenedioxyphenyl)-trans-3-tetradecene (12), 2-oxo-16-(3',4'-methylenedioxyphenyl)-trans-3-hexadecene (13), and 2-oxo-16-phenyl-3-hexadecane (14). In addition, p-eugenol (15), methyleugenol (16), Z-piperolide (17), demethoxyyangonin (18), 5,6-dehydro-7,8-dihydromethysticin (19), cepharanone B (20), piperolactam A (21), cepharadione B (22), N-trans-feruloyltyramine (23), and N-trans-(p-coumaroyl)tyramine (24) were obtained from the anti-TBC stem extract of the plant. GC-MS and HPLC analyses of the essential oils of the leaves and stem revealed that safrol (25) was the major component of the oils. Compounds 2, 3, 6, 18-21, and 24 inhibited the growth of Mycobacterium tuberculosis when tested by the MABA assay, with MIC values ranging from 4 to 64 microg/mL.     

Anti-inflammatory neolignans from Piper kadsura

Two new neolignans, piperkadsin A (1) and piperkadsin B (2), as well as 11 known neolignans, three known alkaloids, the highly oxygenated compound (+)-crotepoxide, and stigmasterol were isolated from the stems of Piper kadsura. The anti-inflammatory activities of these compounds were evaluated. Compounds 1, 2, futoquinol (3), piperlactam S (4), and N-p-coumaroyl tyramine (5) showed potent inhibition of PMA-induced ROS production in human polymorphonuclear neutrophils with IC(50) values 4.3 +/-1.0, 12.2 +/- 3.2, 13.1 +/- 5.3, 7.0 +/- 1.9, and 8.4 +/- 1.3 microM, respectively.     

假蒟化学成分的研究

目的研究假蒟Piper sarmentosum Roxb.的化学成分。方法假蒟80%乙醇提取物乙酸乙酯萃取部位采用硅胶柱、Sephedex LH-20、TLC和重结晶等进行分离纯化,根据理化性质及波谱数据鉴定所得化合物的结构。结果从中分离得到8个化合物,分别鉴定为sesamin(1)、pellitorine(2)、1-nitrosoimino-2,4,5-trimethoxybenzene(3)、N-(3-phenylpropanoyl) pyrrole(4)、3-(4′-methoxyphenyl)propanoyl pyrrole(5)、β-sitosterol(6)、piperumbellactam A(7)、6,7-dimethoxy-4-hydroxy-1-naphthoic acid(8)。结论化合物5、7～8为首次从该植物中分离得到。     

Bioactive tetrahydrofuran lignans from Peperomia dindygulensis

Five new tetrahydrofuran lignans (1-5), accompanied by four known compounds, were isolated from the ethyl acetate extract of Peperomia dindygulensis. Structures were elucidated mainly using 1D NMR, 2D NMR, and mass spectroscopic studies. The relative configurations of 1-5 were determined by NOE correlations. Several of the compounds showed weak growth inhibitory activity against three cell lines (WI-38, VA-13, and HepG2). Compound 5 exhibited stronger MDR (multidrug resistance) reversal activity than verapamil at 2.5 microg/mL in a cellular calcein accumulation assay. Compounds 4 and 5 showed weak inhibitory activity against induction of the intercellular adhesion molecule-1 (ICAM-1) in anti-inflammatory activity experiments.     

3-Farnesyl-2-hydroxybenzoic acid is a new anti-Helicobacter pylori compound from Piper multiplinervium

A new prenylated salicylic acid derivative, 3-farnesyl-2-hydroxy benzoic acid (1), was isolated from the leaves of Piper multiplinervium C. DC. (Piperaceae). It showed anti-Helicobacter pylori activity (MIC 37.5 microg/ml) and antimicrobial activity at MICs between 2.5 and 5 microg/ml against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Mycobacterium smegmatis, Pseudomonas aeruginosa and Candida albicans. Its structure was elucidated by means of MS, 1H and 13C NMR. The ethnomedical claim of Piper multiplinervium to treat stomach aches by the Kuna Indians of Panama may be justified by anti-Helicobacter pylori activity of its MeOH extract.     

Bioactive dibenzylbutyrolactone and dibenzylbutanediol lignans from Peperomia duclouxii

Six new dibenzylbutyrolactone (6-11) and two new dibenzylbutanediol lignans (12, 13) were obtained from Peperomia duclouxii. The structures were elucidated mainly by the analysis of NMR and MS data. The anticancer activity against a normal (WI-38) and a simian virus 40-transformed human lung fibroblast cell (VA-13) and a hepatoma G2 cell (HepG2) and the MDR reversal activity of the isolated compounds were examined. Compound 7 showed moderate inhibitory activity against VA-13 and HepG2 with IC(50) values of 23.2 and 26.4 microM, respectively. Compound 2 inhibited the growth of HepG2 cells with an IC(50) of 42.8 microM. Compounds 2 and 13 exhibited stronger MDR reversal activity than verapamil, at 25 and 2.5 microg/mL, respectively, and 4, 5, and 7 showed comparable activity with verapamil, at 25, 25, and 2.5 microg/mL, respectively.