3-O-Glutaryl-dihydrobetulin and related monoacyl derivatives as potent anti-HIV agents

3-O-Acyl-betulin and -dihydrobetulin derivatives were prepared and evaluated for anti-HIV activity. 3-O-Glutaryl-dihydrobetulin (17) demonstrated extremely potent anti-HIV activity with an EC(50) value of 2 x 10(-5) microM and a TI value of 1.12 x 10(6). 3-O-(3',3'-Dimethylsuccinyl)- and 3-O-(3',3'-dimethylglutaryl)-dihydrobetulins (15, 16) were also potent anti-HIV compounds with EC(50) values of 0.0017 and 0.0013 microM, respectively, and TI values of 16,160 and 19,530, respectively.     

3,28-Di-O-(dimethylsuccinyl)-betulin isomers as anti-HIV agents

Four isomers of 3,28-di-O-(dimethylsuccinyl)-betulin were prepared and evaluated for anti-HIV activity against HIV-1 replication in H9 lymphocyte cells. 3-O-(3',3'-Dimethylsuccinyl)-28-O-(2", 2"-dimethvlsuccinyl)-betulin (11) was the most potent anti-HIV compound with an EC5, value of 0.00087 microM and a TI value of 42,400.     

地菍的化学成分(英文)

为了研究野牡丹科药用植物地菍(Melastoma dodecandrum)的化学成分,采用柱层析方法分离鉴定了15个化合物,通过波谱分析及对比文献等方法鉴定为4-O-β-D-吡喃葡萄糖基-3,3',4'-三甲氧基鞣花酸(1),槲皮素3-O-刺槐二糖苷(2),8-C-吡喃葡萄糖基-5,7,3',4'-四羟基黄酮(3),3-O-β-D-吡喃葡萄糖基-4',5,7-三羟基黄酮(4),6-C-吡喃葡萄糖基-4',5,7-三羟基黄酮(5),3-hydroxy-22(29)-hopen-23-oic acid(6),2,3-dihydroxy-9(11)-fernen-23-oic acid(7),3β-sitosterol laminaribioside(8),姜糖酯B(9),3-O-β-D-galactopyranoside-glycerol1-alkanoates(10),胡萝卜苷(11),β-谷甾醇(12),二十八烷醇(13),二十四烷酸(14)以及三十四烷(15)化合物结构。所有化合物均为首次从该植物中分离得到。     

Cyclic acetals of 4,1',6'-trichloro-4,1',6'-trideoxy-galacto-sucrose and their conversion into methyl ether derivatives

The acid-catalysed reaction of 4,1',6'-trichloro-4,1',6'-trideoxy-galacto- sucrose (1) with 5.5 equiv. of 2-methoxypropene in N,N-dimethylformamide followed by acetylation gave 3',4'-di-O-acetyl-4,1',6'-trichloro-4,1',6'-trideoxy-2,3-O- isopropylidene-6-O-(1-methoxy-1-methylethyl)-galacto-sucrose (2, 2%), 6,3',4'- tri- O-acetyl-4,1',6'-trichloro-4,1',6'-trideoxy-2,3-O-isopropylidene-galacto -sucrose (3, 31%), 3',4'-di-O-acetyl-4,1',6'-trichloro-4,1',6'-trideoxy-2,3-O- isopropylidene- galacto-sucrose (4, 38%), 3'-O-acetyl-4,1',6'-trichloro-4,1',6'-trideoxy-2,3-O- isopropylidene- galacto-sucrose (5, 13%), and 2,3',4'-tri-O-acetyl-4,1',6'-trichloro- 4,1',6'-trideoxy-galacto-sucrose (6, 13%). Methylation of 4 followed by removal of the protecting groups gave 4,1',6'-trichloro-4,1',6'-trideoxy-6-O-methyl- galacto- sucrose (8). 4,1',6'-Trichloro-4,1',6'-trideoxy-3-O-methyl-galacto-sucrose (11) was synthesised from 6 by preferential tert-butyldiphenylsilylation of HO-6 followed by methylation and removal of the protecting groups. Likewise, 4,1',6'-trichloro- 4,1',6'-trideoxy-4'-O-methyl-galacto-sucrose (14) was synthesised from 5. Treatment of 3 with aqueous acetic acid followed by methylation and removal of the protecting groups afforded 4,1',6'-trichloro-4,1'6'-trideoxy-2,3-di-O-methyl- galacto-sucrose (17).     

Three acetylated flavonol glycosides from Forsteronia refracta that specifically inhibit p90 RSK

A survey of plant extracts for the presence of p90 ribosomal S6 kinase (RSK) inhibitors resulted in the isolation of three acetylated flavonol glycosides. Kaempferol 3-O-(2',4'-O-diacetyl-alpha-l-rhamnopyranoside) (1), kaempferol 3-O-(3',4'-O-diacetyl-alpha-l-rhamnopyranoside) (2), and kaempferol-3-O-(4'-O-acetyl-alpha-l-rhamnopyranoside) (3) were isolated from Forsteronia refracta as the first RSK inhibitors. Of these, compound 2 was found to be the best inhibitor with an IC(50) value of 89 nM.     

Antioxidant flavonoids from leaves of Polygonum hydropiper L

Ten flavonoid compounds were isolated from the dried leaves of Polygonum hydropiper L. (Laksa leaves), and identified as 3-O-alpha-L-rhamnopyranosyloxy-3',4',5,7-tetrahydroxyflavone; 3-O-beta-D-glucopyranosyloxy-4',5,7-trihydroxyflavone; 6-hydroxyapigenin; 6"-O-(3,4,5-trihydroxybenzoyl) 3-O-beta-D-glucopyranosyloxy-3', 4', 5, 7-tetrahydroxyflavone; scutillarein; 6-hydroxyluteolin; 3',4',5,6,7-pentahydroxyflavone; 6-hydroxyluteolin-7-O-beta-D-glucopyranoside; quercetin 3-O-beta-D-glucuronide; 2"-O-(3,4,5-trihydroxybenzoyl) quercitrin; quercetin. Evaluation of the antioxidative activity, conducted in vitro, by using electron spin resonance (ESR) and ultraviolet visible (UV-vis) spectrophotometric assays, showed that these isolated flavonoids possess strong antioxidative capabilities. Measurement of the Trolox equivalent antioxidant capacity (TEAC) values, against ABTS (2,2'-azinobis(3-ethyl-benzo-thiazoline-6-sulphonic acid) radicals and phenyl-tert-butyl nitrone (PBN) azo initiator (AI) also showed strong anti-oxidative activity. The most powerful of the antioxidants was 2"-O-(3,4,5-trihydroxybenzoyl) quercitrin (galloyl quercitrin). A combination of two flavonoid compounds was tested for synergistic anti-oxidative capacity, but no significant improvement was observed.     

Design and synthesis of novel 2',3'-dideoxy-4'-selenonucleosides as potential antiviral agents

On the basis of potent anti-HIV activity of 2',3'-dideoxynucleosides (ddNs), their bioisosteric analogues, 2',3'-dideoxy-4'-selenonucleosides (4'-seleno-ddNs) were first synthesized from a chiral template, d-glutamic acid using stereoselective ring-closure reaction of the dimesylate with Se(2-) and Pummerer type condensation of the selenoxide with nucleobases as key steps. X-ray crystallographic analysis indicated that 4'-seleno-ddNs adopted the same C2'-endo/C3'-exo (South) conformation as anti-HIV active ddNs, but did not show anti-HIV activity, indicating that RT seems to prefer the C2'-exo/C3'-endo (North) conformation on binding with their triphosphates.     

Rare biscoumarins and a chlorogenic acid derivative from Erycibe obtusifolia

Three coumarins, 7,7'-dihydroxy-6,6'-dimethoxy-3,3'-biscoumarin (1), 7,7'-dihydroxy-6,6'-dimethoxy-8,8'-biscoumarin (2) and 7-O-[4'-O-(3',4'-dihydroxycinnamyl)-beta-d-glucopyranosyl]-6-methoxycoumarin (3), and a chlorogenic acid derivative, methyl-3-O-(4'-hydroxy-3',5'-dimethoxybenzoyl)-chlorogenate (4) were isolated from the roots of Erycibe obtusifolia along with four known coumarins, scopoletin (5), scopolin (6), cleomiscosin A (7) and cleomiscosin B (8). Their structures were elucidated by spectroscopic methods. Among them, compounds (1) and (2) are rare carbon-carbon linked symmetrical biscoumarins.     

Phenylpropanoid glucosides from leaves of Coussarea hydrangeifolia (Rubiaceae)

Phenylpropanoid glycosides, 1'-O-benzyl-alpha-L-rhamnopyranosyl-(1'-->6')-beta-D-glucopyranoside (1) and alpha-L-xylopyranosyl-(4'-->2')-(3-O-beta-D-glucopyranosyl)-1'-O-E-caffeoyl-beta-D-glucopyranoside (2), together with the known derivatives, 1,6-di-O-caffeoyl-beta-D-glucopyranoside (3), 1-O-(E)-caffeoyl-beta-D-glucopyranoside (4) and 1-O-(E)-feruloyl-beta-D-glucopyranoside (5), were isolated from leaves of Coussarea hydrangeifolia. Their structures were determined by IR, HRESIMS, and 1D and 2D NMR experiments, and their antioxidant activities, evaluated by assaying the free radical scavenging capacity using the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical as substrate. The antioxidant activities of 3 and 4 (IC50 values of 15.0 and 19.2 microM, respectively) were comparable to that of the standard positive control caffeic acid, whilst 2 and 5 were only weakly active and 1 was inactive.     

白粉藤的木脂素和三萜成分

从白粉藤（Cissus repens Lank）地上部分分离得到5个木脂素和8个三萜,其中一个木脂素是新化合物,它的结构通过波谱分析和碱水解的方法鉴定为：（＋）-异落叶松树脂醇-9′-（2-对-香豆酰）-O-β-D-吡喃木糖苷（1）。其余化合物分别是：（＋）-异落叶松树脂醇-9′-O-β-D-吡喃木糖苷（2）,（＋）-Lyoniside（3）,（—）-开环异落叶松树脂醇-9-O-β-D-吡喃木糖苷（4）,（7′R,8′S）-4′-hydroxy-3′,5-dimethoxy-7,8′-dihydrobenzofuran-1-propanolneolignan-9′-O-β-D-xylopyranoside（5）,木栓酮（6）,表木栓醇（7）,蒲公英赛醇乙酸酯（8）,熊果酸（9）,2α-羟基乌索酸（10）,积雪草酸（11）,Niga-ichigoside F1（12）,羽扇豆醇（13）。这些化合物都是首次从该植物中分离得到。     

Iridoid glycosides from Gmelina arborea

Three iridoid glycosides 6-O-(3'-O-benzoyl)-alpha-l-rhamnopyranosylcatalpol (1a), 6-O-(3'-O-trans-cinnamoyl)-alpha-l-rhamnopyranosylcatalpol (2a) and 6-O-(3'-O-cis-cinnamoyl)-alpha-l-rhamnopyranosylcatalpol (3a) were isolated from aerial parts of Gmelina arborea and structures were elucidated by spectral analysis. Additionally a known iridoid 6-O-(3', 4'-O-dibenzoyl)-alpha-l-rhamnopyranosylcatalpol (4) was also isolated and identified.     

2' (or 3')-O-(2, 4, 6-trinitrophenyl)adenosine 5'-triphosphate as a probe for the binding site of heavy meromyosin ATPase.

1. From NMR, IR and visible absorption studies of 2'(or 3')-O-(2, 4, 6-trinitrophenyl)-adenosine 5'-triphosphate (TNP-ATP), 2'(or 3')-O-(2, 4, 6-trinitrophenyl) adenosine (TNP-Ad(, and 1-(2'-hydroxyethoxy)-2, 4, 6-trinitrobenzene (TNP-EG), it was concluded that there is an intramolecular interaction between the base and 2, 4, 6-trinitrophenyl (TNP) moieties in the TNP-ATP molecule. 2. A broad new absorption band was observed in the 530-630 nm region when excess indole was added to reaction mixtures containing TNP-ATP dissolved in 50% methanol or dimethyl sulfoxide. On addition of aromatic amino acid derivatives, methanol or dimethyl sulfoxide. On addition of aromatic amino acid derivatives, TNP-ATP and TNP-Ad underwent spectral shifts in the 400-550 nm region. The formation of a 1:1 complex apparently occurred between TNP-ATP and aromatic amino acid derivatives, and the complex with N-acetyltryptophan was stable in 50% methanol. The difference spectrum of TNP-EG vs. TNP-ATP closely resembled that induced by the addition of N-acetyltryptophan to the TNP-ATP solution. 3. The binding of 2'(or 3')-O-(2, 4, 6-trinitrophenyl)adenosine 5'-diphosphate (TNP-ADP) to heavy meromyosin (HMM) was studied by the rapid gel equilibrium method using Sephadex G-25. A dissociation constant of 1.4 muM and a maximum binding number of 1.8 were obtained in 0.15 M KCl, 10 mM MgCl2, and 50 mM Tris-HCl (pH 8.0) at 25 degrees. TNP-ADP bound to the enzyme caused a characteristic spectral shift in the visible region. This spectral shift was explained in terms of an interaction between tryptophanyl residues and the adenine base of TNP-ADP bound to the enzyme. TNP-ADP quenched the tryptophanyl fluorescence, but TNP-EG and TNP-Ad did not. In the presence of 6 M guanidine hydrochloride, TNP-ADP scarcely quenched the tryptophanyl fluorescence, its effect being comparable to that of TNP-Ad.     

Enzymatic polymerization of coniferyl alcohol in the presence of cyclodextrins

The dehydrogenative polymerization of coniferyl alcohol by horseradish peroxidase was performed in 0.10 M phosphate buffer at 27 degrees C. Dehydrogenative polymer (DHP) from coniferyl alcohol was characterized by size exclusion chromatography (SEC) and nuclear magnetic resonance (NMR) spectroscopy. The ratio of 8-O-4':8-5':8-8' linkages was determined by the 1H NMR spectrum of DHP acetate which had good solubility. In "end-wise like" polymerization (the slow addition of hydrogen peroxide), addition of alpha-cyclodextrin to the medium led to DHP with increased 8-O-4' content and a decrease in 8-5' linkages. Under higher pH conditions, DHP with higher 8-O-4' and 8-5' content was obtained in the presence of alpha-cyclodextrin. In the end-wise polymerization (the slow additions of coniferyl alcohol and hydrogen peroxide), using alpha-cyclodextrin also gave DHP with a 8-O-4' richer structure than that prepared in no additive system. The analysis of thioacidolysis products from DHP supported the results of the alpha-cyclodextrin effects on the 8-O-4'-rich structure of DHP. The 8-O-4' structure in DHP prepared in the presence of alpha-cyclodextrin had racemic form as shown by ozonation.     

Evaluation of natural antioxidants of Leuzea carthamoides as a result of a screening study of 88 plant extracts from the European Asteraceae and Cichoriaceae

In recently, there has been a great interest in natural antioxidants as bioactive components of food, nutraceuticals or potential drugs against several diseases. In our study, 88 extracts from various parts of plants from European Asteraceae and Cichoriaceae were assayed for radical scavenging activity by means of DPPH (1,1-diphenyl-2-picryl hydrazyl radical) test using the SIA (Sequential injection analysis) method developed for this purpose in our laboratory. DPPH radical scavenging activity of all tested plant extracts was evaluated according to the IC(50) parameter. 29 extracts exhibited IC(50) value lower than 0.1 mg/mL. The leaves of Leuzea carthamoides (IC(50) = 0.046 mg/mL) were chosen as the most promising sample for a subsequent phytochemical study, which resulted in isolation of seven natural compounds, namely, 4',5,7-trihydroxy-6-methoxyflavone (hispidulin) (1), 5, 7, 3', 4'- tetrahydroxyflavanone (eriodictyol) (2), 3',4',5,7-pentahydroxy-6-methoxyflavonol (patuletin) (3), eriodictyol-7-beta-glucopyranoside (4), 6-hydroxykaempferol-7-O-(6'-O-acetyl-beta-D-glucopyranoside) (5), 4-hydroxybenzoic acid (6) and 3,4-dihydroxybenzoic acid (protocatechuic acid) (7). Antioxidant activity of the isolated compounds was evaluated by DPPH test and ferric reducing antioxidant power (FRAP) test and compared with trolox and quercetin. Both tests evaluated the flavonoid (5) as the most active antioxidant. This result was confirmed by comparison with known data concerning the structure/activity relationships of flavonoids.     

Anti-HIV drugs: comparative toxicities in murine fetal liver and bone marrow erythroid progenitor cells

The toxicity of anti-HIV drugs, 3'-azido-3'-deoxythymidine (zidovudine, AZT), 2',3'-dideoxycytidine (DDC), 2',3'-dideoxy-2',3'-didehydrothymidine (d4T) and ribavirin was studied in vitro in murine fetal liver cells (FLC) and in bone marrow cells. These studies indicate that d4T is the least toxic drug and ribavirin is the most toxic agent in both models. However, the murine FLC system was found to be a more sensitive model for the assessment of toxicity of anti-HIV agents towards erythroid progenitor cells as indicated by the IC50 values.     

半卧狗娃花中的黄酮类化合物

从半卧狗娃花(Heteropappus semiprost Griers)全草的乙醇提取物中分离并鉴定了7个黄酮类化合物,通过波谱分析及化学方法鉴定其结构为:3′,4′,5,7-四羟基黄酮(1),3′-甲氧基槲皮素(2),槲皮素-3-O-α-L-吡喃鼠李糖甙(3),槲皮素-3-O-β-D-吡喃半乳糖甙(4),异鼠李亭-3-O-β-D-吡喃半乳糖甙(5),槲皮素-3-O-α-L-吡喃鼠李糖(1→6)-β-D-吡喃葡萄糖甙(6),异鼠李亭-3-O-α-L-吡喃鼠李糖(1→6)-β-D-吡喃葡萄糖甙(7),其中化合物1~5为首次从本属植物中分离得到。     

Design and synthesis of dually branched 5'-norcarbocyclic adenosine phosphonodiester analogue as a new anti-HIV prodrug

A novel 3',4'-dimethyl-5'-norcarbocyclic adenosine phosphonic acid was prepared using acyclic stereoselective route from 4-hydroxybutan-2-one (4). To improve the cellular permeability and enhance the anti-HIV activity of this phosphonic acid, a (bis)SATE phosphonodiester nucleoside prodrug (20) was prepared and its chemical stability was evaluated. The newly synthesized bis(SATE) analogue (20) and its parent nucleoside phosphonic acid (18) were assayed for anti-HIV activity using an in vitro assay system in a CEM cell line.     

Chemical structure of the lipid A component of Plesiomonas shigelloides and its taxonomical significance

Abstract The chemical structure of the lipid A moiety of the lipopolysaccharide of the type strain of Plesiomonas shigelloides was elucidated. It consists of a β-(1 → 6)-linked glucosamine disaccharide carrying phosphate groups at C-1 of the reducing and at C-4' of the non-reducing glucosamine. It contains a total of 6 residues of fatty acids, 2 amide-linked and 4 ester-linked. The amino groups of the backbone disaccharide are N -acylated by substituted 3-hydroxyacyl residues: at the reducing glucosamine by 3-O-(14:0)14:0; and at the non-reducing glucosamine by 3-O-(12:0)14:0.
Two residues of 3-hydroxytetradecanoic acid are linked to C-3 and C-3' of the glucosamine residues; the hydroxy groups of these ester-linked 3-hydroxytetradecanoic acids are unsubstituted. In free lipid A, the hydroxyl groups at C-4 and C-6' are unsubstituted, indicating that the 2-keto-3-deoxyoctonic acid (KDO) is linked to C-6' of the non-reducing glucosamine, as was shown with enterobacterial lipid A. The taxonomical significance of these structural details is discussed.     

Synthesis of the tetrasaccharide core region of antigenic lipo-oligosaccharides characteristic of Mycobacterium kansasii

The oligosaccharide core region, beta-D-Glcp-(1----3)-beta-D-Glcp-(1----4)-alpha-D-Glcp- 1----1)-alpha-D-Glcp (1), of the lipo-oligosaccharide-type antigens isolated from M. kansasii has been synthesised from 2,3,2',3',4',6'-hexa-O-benzyl-6-O-(1-phenylethyl)-alpha, alpha-trehalose (4). Compound 4 was obtained by LiAlH4-AlCl3-type hydrogenolysis of 2,3,2',3',4',6'-hexa-O-benzyl-4,6-O-(S)-(1-phenylethylidene)-alpha , alpha-trehalose. The beta-laminaribiosyl part of the molecule was built-up by sequential glycosylation steps using 2,4,6-tri-O-acetyl-3-O-allyl-alpha-D-glucopyranosyl bromide in the presence of HgBr2 and methyl 2,3,4,6-tetra-O-acetyl-1-thio-beta-D-glucopyranoside promoted by methyl triflate. The complete a priori 13C-n.m.r. spectrum assignment of 1 was achieved by applying 2D methods.