Design of potent and selective linear antagonists of vasopressor (V1-receptor) responses to vasopressin

We report the solid-phase synthesis of 21 linear analogues of A and D, two nonselective antagonists of the vasopressor (V1) and antidiuretic (V2) responses to arginine vasopressin (AVP). A is Aaa-D-Tyr(Et)-Phe-Val-Asn-Abu-Pro-Arg-Arg-NH2 (where Aaa = adamantylacetyl at position 1). D is the des-Arg9 analogue of A. Nine new analogues of A (1-9) and 12 new analogues of D (10-21) were obtained. The following substitutions either alone or in combination were incorporated in A and/or in D: phenylacetic acid (Phaa) and tert-butylacetic acid (t-Baa) at position 1; D-Tyr2, D-Tyr(Me)2; Gln4; Arg6, Lys6, Orn6, MeAla7. The nine new analogues of A are (1) [Arg6], (2) [Lys6], (3) [Orn6], (4) [Phaa1,Lys6], (5) [Phaa1,Orn6], (6) [D-Tyr2], (7) [D-Tyr2,Arg6], (8) [Phaa1,D-Tyr2], (9) [Phaa1,D-Tyr2,Arg6]. The 12 new analogues of D are (10) [Arg6], (11) [Lys6], (12) [Orn6], (13) [Phaa1,Lys6], (14) [Phaa1,Gln4,Lys6], (15) [Phaa,D-Tyr(Me)2,Lys6], (16) [Phaa,D-Tyr(Me)2,Gln4,Lys6], (17) [Phaa1,D-Tyr2,Gln4,Lys6], (18) [t-Baa1,Lys6], (19) [t-Baa1,Gln4,Lys6], (20) [Arg6,MeAla7], (21) [t-Baa1,Arg6,MeAla7]. All 21 peptides were examined for agonistic and antagonistic potencies in AVP V2 and V1 assays in rats. With the exception of 6, the eight remaining new analogues of A are equipotent or more potent than A as V1 antagonists. Peptides 2-9 are less potent than A as V2 antagonists. Three, 4, 5, and 9, exhibit significant gains in anti-V1/anti-V2 selectivities (selectivity ratio = 41, 14, and infinite, respectively), compared to A (anti-V1, pA2 = 7.75 +/- 0.07; selectivity ratio = 0.44). Peptide 9 is unique in both series. It is a highly potent V1 antagonist (anti-V1 pA2 = 8.62 +/- 0.11 and is the first linear peptide to exhibit substantial antidiuretic agonism (4.1 +/- 0.2 units/mg). With the exception of 12, the remaining 11 analogues of D are 8-40 times more potent than D as V1 antagonists. Eight of these peptides exhibit significant gains in anti-V1/anti-V2 selectivities compared to D (anti-V1 pA2 = 7.43 +/- 0.06; selectivity ratio = 1.6).(ABSTRACT TRUNCATED AT 400 WORDS)     

Two new monoterpene glycosides and a new (+)-jasmololone glucoside from Bidens parviflora Willd

Two new monoterpene glycosides named bidensmenthosides A, B and a new (+)-jasmololone glucoside, were isolated from the air-dried whole plant of Bidens parviflora Willd. Their structures were determined as (1S, 3S, 4R)-3-hydroxy-p-menth-6-one 3-O-beta-D-glucopyranoside (1), (3R, 4R)-3-hydroxy-p-menth-1 (2)-en-6-one 3-O-beta-D-glucopyranoside (2) and (4R)-hydroxy-3-methyl-2-(2 Z-pentenyl)-cyclopent-2-enone 4-O-beta-D-glucopyranoside (3) based on spectroscopic analysis and physiochemical properties, respectively. The bidensmenthosides A, B and aglycone of 3 were found to reduce 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radicals.     

木立芦荟中BACE抑制活性成分的研究

目的从木立芦荟(Aloe arborescens)中寻找新的BACE(β-分泌酶)抑制活性成分。方法用硅胶正相色谱及反相色谱技术进行活性成分的分离纯化，根据理化性质、光谱资料进行结构鉴定。结果从木立芦荟95%乙醇提取物的乙酸乙酯部分和正丁醇部分，分离得到了8个化合物：异丁酰基芦荟宁A(1)，芦荟宁A(2)，芦荟大黄素(3)，(E)-2-acetonyl-8-(2′-O-feruloxyl)-β-D-glucopyranosyl-7-methoxy-5-methyl-chromone (4)，7-O-methyl aloeresin A (5)，芦荟苷A(6)，elgonica-dimer A (7)和elgonica-dimer B (8)。结论化合物1为新化合物，化合物4为首次从该植物中分离得到。活性测试结果表明，化合物2，4，5，6对BACE有一定的抑制活性。     

Antibacterial alkaloids from Zanthoxylum rhoifolium

Two new dihydrobenzophenanthridine-type alkaloids, 6-methoxy dioxolo[4',5':4,5]benzo[c] dioxolo[4,5- j]phenanthridine (1) and 2,3,13-trimethoxy-5,11a-dihydro dioxolo[4',5':4,5]benzo[c]phenanthridine (2) were isolated from the stem bark of Zanthoxylum rhoifolium, together with four other previously known benzophenanthridine alkaloids, 6-acetonyldihydronitidine (3) [= 8-acetonyldihydronitidine], 6-acetonyldihydroavicine (4) [= 8-acetonyldihydroavicine], 6-acetonyldihydrochelerythrine (5) and xanthoxyline (6). The structures were elucidated mainly by spectroscopic methods, including 1D and 2D NMR spectroscopy. For alkaloids 1 and 2 we propose the trivial names rhoifolines A and B. The crude plant extracts and the alkaloids 3, 4 and 6 showed activity against Gram (+/-) bacteria, while the new alkaloids 1 and 2 were inactive.     

Antimicrobial compounds from Pimpinella species growing in Turkey

A new, 4-(2-propenyl)-phenyl angelate ( 1) and four known phenylpropanoids ( 2 - 5), were isolated from Pimpinella isaurica, a species endemic in Turkey. One new sesquiterpene, 1-methyl-4-(5-methyl-1-methylenehex-4-enyl)-7-oxabicyclo[4.1.0]heptane ( 6) was obtained from P. aurea and two known phenylpropanoids were isolated ( 7, 8), from P. corymbosa. The structure elucidation of the new compounds 1 and 6 was achieved by a combination of one- ( (1)H, and (13)C) and two-dimensional NMR techniques (G-DQF-COSY, G-HMQC, and G-HMBC) and LC-ESI-FTMS. Compounds 1, 2, 4, 6, 7, 8 have been evaluated for their antimalarial and antimicrobial activities. Compound 1, 2, 4, 6, 8 had antimicrobial activity against Mycobacterium intracellulare with IC (50) values of 7.0, 15.0, 2.5, 10.0 and 1.5 microg/mL, respectively.     

黄丝郁金中的生物碱和倍半萜类成分

姜科植物姜黄(Curcuma longa)的块根称为黄丝郁金，是常用中药郁金的来源之一。为了研究黄丝郁金的利胆活性成分，采用柱色谱法对姜黄干燥块根的化学成分进行了研究。本文主要报道从中分离得到的1个喹啉类生物碱2-(2′-methyl-1′-propenyl)-4,6-dimethyl-7-hydroxyquinoline (1)，7个没药烷型倍半萜2,5-dihydroxybisabola-3,10-diene (2), 4,5-dihydroxybisabola-2,10-diene (3), turmeronol A (4), bisacurone (5), bisacurone A (6), bisacurone B (7)和bisacurone C (8)，以及dehydrozingerone (9)和zingerone (10)的分离和鉴定。化合物1为一个新的生物碱类化合物，化合物6～8为首次从姜黄中分得，化合物9～10为首次从姜黄属植物中分离得到。     

猫儿刺的化学成分

猫儿刺(Ilex pernyi)为冬青科冬青属植物，民间常用于清热解毒，润肺止咳。本文对猫儿刺叶的化学成分进行研究，应用硅胶、Sephadex LH-20、反相硅胶和半制备RP-HPLC等分离纯化方法从其乙醇提取物中分离并鉴定了6个化合物：(E)-异丁香酚-α-L-吡喃阿拉伯糖基(1→6)- β-D-吡喃葡糖苷(1)，山柰酚-3-O-桑布双糖苷(2)，槲皮素-3-O-桑布双糖苷(3)，异槲皮苷(4)，丁香树脂酚葡糖苷(5)，反枝苋苷IV(6)。其中，化合物1为一新酚苷类化合物，命名为猫儿刺酚苷A。化合物2～6为首次从该植物中分离得到。     

Acylphloroglucinol glycosides from the fruits of Pyracantha fortuneana

Three new acylphloroglucinol glycosides, namely pyrafortunosides A (1), B (2) and C (3), together with three known glycosides (4-6), were isolated from the fruits of Pyracantha fortuneana (Maxim.) Li. Their structures were established to be 2,4,6-trihydroxy-acetophenone-6-O-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (1), 2,4,6-trihydroxy-benzophenone-6-O-alpha-L-rhamno-pyranosyl-(1-->6)-beta-D-glucopyranoside (2), 2,4,6-trihydroxy-benzophenone-6-O-beta-D-apiofuranosyl-(1-->6)-beta-D-gluco-pyranoside (3), garcimangosone D (4), 2,4,6-trihydroxy-acetophenone-6-O-beta-D-glucopyranoside (5), and 2,4,6-trihydroxy-acetophenone-4-O-beta-D-glucopyranoside (6) by spectral analysis. The three known glycosides (4-6) were obtained from this genus for the first time.     

Phenolic glycosides from Potalia amara

Investigation of the stem bark of the unique Amazonian herbal plant Potalia amara yielded two new phenolic glycosides, potalioside A (1) and B (2), along with di-O-methylcrenatin (3), 2,6-dimethoxy-4-hydroxyphenol 1-glucoside and sweroside. The structures of potalioside A and B were established by interpretation of spectral data as 4-hydroxymethyl-2,6-dimethoxyphenyl 1-O-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranoside and 4-hydroxymethyl-2,6-dimethoxyphenyl 1-O-beta- D-xylopyranosyl(1-->6)- beta-D-glucopyranoside, respectively.     

New guaiane sesquiterpenes and furanocoumarins from Notopterygium incisum

In addition to twenty-nine known compounds, two new guaiane sesquiterpenes and two new furanocoumarins were isolated from the chloroform extract of the rhizomes of Notopterygium incisum. The new structures were elucidated by means of spectroscopic methods including 2 D NMR techniques and mass spectrometry to be 8 beta-acetoxy-4 alpha,6 alpha-dihydroxy-1 alpha,5 alpha( H)-guai-9-ene (incisumdiol A, 1), 4 alpha,6 alpha-dihydroxy-1 alpha,5 alpha( H)-guai-9-ene (incisumdiol B, 2), 5-[(2 E,5 Z)-7-hydroxy-3,7-dimethyl-2,5-octadienoxy]psoralene ( 3) and 5-[(2,5)-epoxy-3-hydroxy-3,7-dimethyl-6-octenoxy]psoralene ( 4).     

Flavonoids from<Emphasis Type="Italic">Iris spuria</Emphasis> (Zeal) cultivated in Egypt

A new 12a-dehydrorotenoid 1, 11-dihydroxy-9, 10-methylenedioxy-12a-dehydrorotenoid (1), together with a new isoflavonoid glycoside tectorigenin-7-O-beta-glucosyl-4'-O-beta-glucoside (3), were isolated and identified from the rhizomes of I. spuria (Zeal). In addition, 4 known compounds, tectorigenin (2) tectorigenin-7-O-beta-glucosyl (1 --> 6) glucoside (4), tectoridin (a tectorigenin-7-O-beta-glucoside) (5) and tectorigenin-4'-O-beta-glucoside (6) were isolated and identified for the first time from this plant. The structures of the isolated compounds were determined by spectroscopic methods (UV, IR, 1H, 13C-NMR, DEPT, HMQC, NOESY, and HMBC experiments and MS spectrometry) and by comparison with literature data of known compounds. Compounds 2, 4, 5, and 6 are reported for the first time from this plant through the present study.     

Chromone glycosides from Knoxia corymbosa

Four new chromone glycosides, corymbosins K1-K4 (3-6), together with two known compounds, noreugenin (1) and undulatoside A (2), were isolated from the whole plant of Knoxiacorymbosa (Rubiaceae). The structures of the new compounds were established through extensive NMR or X-ray spectroscopic analysis as 7-O-beta-D-allopyranosyl-5-hydroxy-2-methylchromone (corymbosin K1, 3), 7-O-beta-D-6-acetylglucopyranosyl-5-hydroxy-2-methylchromone (corymbosin K2, 4), 7-O-[6-O-(4-O-trans-caffeoyl-beta-D-allopyranosyl)]-beta-D-glucopyranosyl-5-hydroxy-2-methylchromone (corymbosin K3, 5) and 7-O-[6-O-(4-O-trans-feruloyl-beta-D-allopyranosyl)]-beta-D-glucopyranosyl-5-hydroxy-2- methylchromone (corymbosin K4, 6). Compounds 2-5 were subjected to test their immunomodulatory activity invitro.     

Two new ellagic acid glycosides from leaves of Diplopanax stachyanthus

Two new ellagic acid glycosides, named stachyanthuside A (1) and B (6), have been isolated along with four known ellagic compounds (2-5) from the leaves of Diplopanax stachyanthus. The structures of the new compounds were established as 3'-O-methylellagic acid 4-O-beta--glucopyranoside (1) and 3,3',4'-tri-O-methylellagic acid 4-O-beta--(2'-acetyl)-glucopyranoside (6) on the basis of detailed spectroscopic analysis and comparison with related model compounds.     

A new triterpenoid saponin from Albizia julibrissin Durazz

A new triterpenoid, saponin hehuanoside A, was isolated together with the known triterpenoid saponins 2, 3, and 4 from the stem bark of Albizia julibrissin. With the help of chemical and spectral analyzes (IR, MS, 1D-NMR, and 2D-NMR), the structure of the new triterpenoid saponin was elucidated as 21-O-[(6S)-2-trans-2,6-dimethyl-6-O-beta-d-quinovopyranosyl-2,7-octadienoyl]-3-O-beta-d-xylopyranosyl-(1 --> 2)-beta-d-fucopyranosyl-(1 --> 6)-beta-d-2-deoxy-2-acetamidoglucopyrasyl acacic acid 28-O-alpha-l-arabinofuranosyl-(1 --> 4)-[-beta-d-glucopyranosyl-(1 --> 3)]-alpha-l-rhamnopyranosyl-(1 --> 2)-beta-d-glucopyranosyl ester (1). Three known triterpenoid saponins 2-4 were identified on the basis of spectroscopic data.     

A new triterpenoid saponin from Albizia julibrissin Durazz

A new triterpenoid, saponin hehuanoside A, was isolated together with the known triterpenoid saponins 2, 3, and 4 from the stem bark of Albizia julibrissin. With the help of chemical and spectral analyzes (IR, MS, 1D-NMR, and 2D-NMR), the structure of the new triterpenoid saponin was elucidated as 21-O-[(6S)-2-trans-2,6-dimethyl-6-O-beta-d-quinovopyranosyl-2,7-octadienoyl]-3-O-beta-d-xylopyranosyl-(1 --> 2)-beta-d-fucopyranosyl-(1 --> 6)-beta-d-2-deoxy-2-acetamidoglucopyrasyl acacic acid 28-O-alpha-l-arabinofuranosyl-(1 --> 4)-[-beta-d-glucopyranosyl-(1 --> 3)]-alpha-l-rhamnopyranosyl-(1 --> 2)-beta-d-glucopyranosyl ester (1). Three known triterpenoid saponins 2-4 were identified on the basis of spectroscopic data.     

Novel N-[omega-[4-(2-methoxyphenyl)piperazin-1-yl]-ethyl]pyrid-2(1H)-ones with diversified 5-HT1A receptor activity

Novel omega-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl derivatives 1-6 containing 4-, 5- and/or 6-arylsubstituted pyrid-2(1H)-one moiety were synthesized. All the new compounds were examined in vitro to assess their 5-HT1A and 5-HT2A receptor affinities. Compounds 3 and 4 with a 5- or a 6-phenylsubstituted pyridone ring demonstrated high 5-HT1A receptor affinity (Ki = 17 and 38 nM, respectively) and were tested in behavioral functional models. Derivative 3 can be regarded as a weak 5-HT1A postsynaptic antagonist, whereas 4 showed features of a weak partial agonist of 5-HT1A receptors (an agonist of pre- and an antagonist of postsynaptic ones). Binding affinities and in vivo results were discussed in comparison with those for the previously described tetramethylene analogs. The obtained results showed that the shortening of the aliphatic chain to two methylene groups exposed the intrinsic activity of the ligand 4 at 5-HT1A receptor sites.     

Triterpenoid saponins from Clematis tangutica

Two new triterpenoid saponins, tanguticoside A and B along with seven known saponins vitalboside B, alpha-hederin, saponin PK, beta-hederin, saponin PJ3, saponin PE, and ciwujianoside A were isolated from aerial part of Clematis tangutica. By chemical and spectral evidences methods, the structures of tanguticoside A and B were elucidated as 3-O-beta-D-glucopyranosylhederagenin 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside and 3-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosylhederagenin 28-O-alpha-D-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside, respectively.     

New citrinin derivatives isolated from Penicillium citrinum

Three new coupling compounds derived from citrinin (9) and 2,3,4-trimethyl-5,7-dihydroxy-2,3-dihydrobenzofuran (8) – penicitrinone A (1), penicitrinol A (2) and penicitrinone B (3) – and a new citrinin derivative – decarboxydihydrocitrinin (4) – were isolated along with 3-methoxy-1-methyl-4(1H)-quinolone (5), quinolactacin A2 (6), dihydrocitrinone (7), 2,3,4-trimethyl-5,7-dihydroxy-2,3-dihydrobenzofuran (8), citrinin (9), quinocitrinin A or B (10), and decarboxydihydrocitrinone (11) from the extract of Penicillium citrinum IFM 53298. The relative structures of compounds 1–4 were confirmed on the basis of spectroscopic investigations and chemical correlations. Citrinin (9) and quinolactacin A2 (6) both showed antifungal activity.     

Cytotoxic terpenoid and immunosuppressive phenolic glycosides from the root bark of Dictamnus dasycarpus

Five new compounds, two degraded terpene glycosides, dasycarpusides A and B (1, 2), and three phenolic glycosides, 2-methoxy-4-hydroxymethylphenol 1-O-alpha-rhamnopyranosyl-(1"-->6')- beta-glucopyranoside ( 3), 2-methoxy-4-acetylphenol 1-O-alpha-rhamnopyranosyl-(1"-->6')-beta-glucopyranoside (4), and 2-methoxy-4-(8-hydroxyethyl)-phenol 1-O-alpha-rhamnopyranosyl-(1"-->6')-beta-glucopyranoside (5), were isolated from the water-soluble constituents of the root bark of Dictamnus dasycarpus Turcz.(Rutaceae). Their structures were elucidated by spectroscopic analysis and chemical evidence. Moreover, it was found that dasycarpuside A (1) showed weak cytotoxic activity against A-549 (human lung adenocarcinoma) cell line, while 4 and 5 showed more remarkable activity of inhibiting the proliferation of T-cells in vitro.     

Triterpenoid saponins from Stauntonia chinensis

A new triterpenoid saponin, named stauntoside A (1) along with four known saponins (2,3,4,5) was isolated from Stauntonia chinensis DC., (Lardizabalaceae). Their structures were elucidated by spectroscopic analysis and chemical methods as 3-O-alpha-L-arabinopyranosyl-30-norhederagenin -28-O-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranosyl ester (1), 3-O-alpha-L-arabinopyranosyl-30- norhederagenin-28-O-alpha-L-rhamnopyranosyl-(1 --> 4)-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranosyl ester (2), 3-O-alpha-L-rhamnopyranosyl-(1 --> 2)-alpha-L-arabinopyranosyl-30-norhederagenin-28-O-alpha-L- rhamnopyranosyl-(1 --> 4)-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranosyl ester (3), 3-O-alpha-L- arabinopyranosyl-hederagenin-28-O-alpha-L-rhamnopyranosyl-(1 --> 4)-beta-D-glucopyranosyl-(1 --> 6)-beta-D- glucopyranosyl ester (4), 3-O-alpha-L-rhamnopyranosyl-(1 --> 2)-alpha-L-arabinopyranosyl-hederagenin -28-O-alpha-L-rhamnopyranosyl-(1 --> 4)-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranosyl ester (5). The (1)H and (13)C NMR data for Glycoside L-G1 or Sinofoside A are paradox in the reported before. Thus, the structure elucidation of saponin 2, known as Glycoside L-G1 or Sinofoside A, was discussed and the unambiguous assignments were given.