Two new podophyllotoxin glucosides from Sinopodophyllum emodi (Wall.) Ying.

Two new aryltetralin-type lignans, isopodophyllotoxin 7'-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside (1) and 4-demethyl-picropodophyllotoxin 7'-O-beta-D-glucopyranoside (2), along with eight known podophyllotoxin derivatives: 4-demethyl-podophyllotoxin 7'-O-beta-D-glucopyranoside (3), podophyllotoxin 7'-O-beta-D-glucopyranoside (4), deoxypodophyllotoxin (5), picropodophyllotoxin (6), podophyllotoxin (7), 4-demethyl-picropodophyllotoxin (8), 4-demethyl-podophyllotoxin (9), and 4-demethyl-deoxypodophyllotoxin (10), were isolated from the roots and rhizomes of Sinopodophyllum emodi (Wall.) Ying (Berberidaceae). Their structures were identified based on NMR spectral data and chemical evidence.     

高异三尖杉酯碱的合成及其立体异构体的分离鉴定

2-氧代-6-甲基庚酰基三尖杉碱(3)与0-(1-甲氧基异丙基)羟基乙酸甲酯(4)在强碱性试剂二异丙胺锂(LDA)存在下,起亲核加成反应,反应中间体5在室温用酸性丙酮水解,得到一种新的三尖杉酯类生物碱一一高异三尖杉酯碱(6c)及其立体异构体(6a、6b、6d)的混合物,产率56%、通过制备薄层层析分得这四个立体异构体,它们的1H NMR和异三尖杉酯碱及其立体异构体的1H NMR类似,推定了它们的绝对构型。初步药理试验表明,高异三尖杉酯碱及其立体异构体的混合物对白血病L7712的DNA合成有明显的抑制作用。     

New lignan glycosides from Chinese medicinal plant,Sinopodophillum emodi

Two new podophillotoxin glucosides, L-picropodophillotpxin 7'-O-(beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside) (2) and L-picropodophillotpxin 7'-O-beta-D-glucopyranoside (3), were isolated from Chinese medicinal plant, Sinopodophillum emodi, together with 4 known compounds, podophillotoxin (1), podorhizol 4'-O-beta-D-glucopyranoside (4), deoxypodophillotoxin (5), and dehydropodophillotoxin (6). The structures of 2 and 3 were finally determined by the extensive decouping and nuclear Overhauser effect (NOE) experiments in NMR spectra and circular dichroism (CD) spectra. Compound 2 is the second example of podophillotoxin diglucoside, and both the first one and 2 were isolated from S. emodi. X-ray crystal structure analysis of 1, 5, and 6 was carried out. Compounds 1 and 5 showed the different conformations from those reported.     

Biflavone glucosides from Ginkgo biloba yellow leaves

Phytochemical investigation of Ginkgo biloba (Ginkgoaceae) has resulted in the isolation of two new biflavone glucosides, ginkgetin 7'-O-beta-D-glucopyranoside (1) and isoginkgetin 7-O-beta-D-glucopyranoside (2). The structures were determined on the basis of chemical and spectroscopic evidences.     

Two new phenolic glycosides from Viburnum plicatum var. plicatum f. plicatum

Two new glycosides, named dideoxyplicatumoside A (1) and erythro-syringylglycerol-beta-O-4'-(+)-isoeucommin A 4'-O-beta-D-glucopyranoside (2), together with seven known compounds, were isolated from the leaves of Viburnum plicatum Thunb. ex Murray var. plicatum f. plicatum. Their structures were established on the basis of NMR, MS and chemical data.     

Preparation of a new chiral stationary phase for HPLC based on the (R)- 1-phenyl-2-(4-methylphenyl)ethylamine amide derivative of (S)-valine and 2-chloro-3,5-dinitrobenzoic acid: enantioseparation of amino acid derivatives and pyrethroid insecticides

A novel chiral stationary phase (CSP) for HPLC was prepared by bonding (R)-1-phenyl-2-(4-methylphenyl)ethylamine amide derivative of (S)-valine to aminopropyl silica gel through a 2-amino-3,5-dinitro-1-carboxamido-benzene unit. The CSP was used for the separation of some amino acid derivatives and pyrethroid insecticides by chiral HPLC. Satisfactory baseline separation required optimization of the variables of mobile phase composition. Use of dichloromethane as modifier in the mobile phase gave baseline separations of amino acid derivatives. The two enantiomers of fenpropathrin and four stereoisomers of fenvalerate were baseline separated using hexane-dichloromethane-ethanol as mobile phase. The results show that the enantioselectivity of the new CSP is better than Pirkle type 1-A column for these compounds. Only partial separations were observed for the stereoisomers of cypermethrin and cyfluthrin, which gave even and eight peaks, respectively.     

A new hydroxyjasmone glucoside and its related compounds from the leaf of thyme

From the polar portion of the methanol extract of thyme (leaf of Thymus vulgaris; Labiatae), which has been used as a stomachic, carminative, a component of prepared cough tea, and as a spice, a new hydroxyjasmone glucoside, (Z)-5'-hydroxyjasmone 5'-O-beta-D-glucopyranoside was isolated together with five related compounds and four aromatic compounds. The structures of the new compound was clarified by spectral investigation.     

A new lignan glycoside from the leaves of Sambucus sieboldiana (Miq.) Blume ex. Graebn

A new lignan glycoside, (-)-massoniresinol 4'-O-beta-D-glucopyranoside (4), was isolated, together with six known ones (1-3, 5-7), from the leaves of Sambucus sieboldiana. Their structures were established on the basis of chemical and spectral data.     

Synthesis of All Four Stereoisomers of (E)-Vitamin KT (Phylloquinone), Analysis of Their Diastereoisomeric and Enantiomeric Purities and Determination of Their Biopotencies

All four stereoisomers of (E)-vitamin Kb i. e. (2¹E, ⁷R, 11¹R)-l (= 1a), (2¹E, 7¹ R, l1¹S)-1 (= 1b), (2¹E, 7¹ S, 11¹S) 1 ( = 1c), and (2¹E, 7¹S, 11¹R)-l ( = Id), have been synthesized in a state of high chemical and stereoisomeric purity. The synthesis of stereoisomers lb-d relied on the use of the optically active Cf¹* and C*¹⁰-building blocks (R)- or (S)-4-(benzyloxy)-3-methylbutanal ((R)- or (S)-2) and (R)- or (S)-citronellal ((R)- or (S)- 3 ) which had been secured by the Rh¹-catalyzed allylamine-to-enamine isomerization technology. For the synthesis of the natural (E)-vitamin-K1 stereoisomer 1a , a new route starting from natural phylol was developed, based on an O-alkylation/rearrangement procedure. A HPLC method was developed which separates with remarkable efficiency all four stereoisomers of (E)- as well as three out of the four stereoisomers of (Z)-vitamin K¹ on optically active poly(trityl methacrylate) as the chiral stationary phase supported on Nucleosil. By this method, the stereoisomeric content of the stereoisomers 1b-d synthesized was shown to be in the range of 96-98 %, while the natural isomer 1a was configurationally uniform. The biological activity of the four (E)-vitamin-K₁ stereoisomers was determined by means of the curative prothrombin time test with vitamin-K-depleted chicks. A high precision of the results was obtained with the recently introduced up-and-down organization of the test and the statistical evaluation according to an estimation procedure. With the natural (E)-vitamin-K₁ stereoisomer 1a as standard (set at 1. 0), activities of 0. 93, 1. 19, and 0. 99 were found for stereoisomers 1b, 1c , and 1d , respectively. Within the confidence limits, these activity ratios can be regarded as identical, A very similar efficacy was obtained by comparison of (E, all-rac )-vitamin K₁ ((2¹E, RS, 11′ RS)- 1 ; equimolar mixture of the four stereoisomers 1a-d) with the natural (E)-vitamin-K₁ stereoisomer 1a ). A synergistic effect was not detectable, as was the case with the eight α-tocopheryl-acetate stereoisomers.     

Three new glycosides from Sinopodophyllum emodi (Wall.) Ying.

Tow new aryltetralin-type lignan glycosides: methyl epipodophyllate 7'-O-beta-D-glucopyranoyl-(1-->6)-beta-D-glucopyranoside (1), 4-demethylepipodophyllotoxin 7'-O-beta-D-glucopyranoside (2), and a new phenyl ethanol glycoside: phenyl ethanol 4-O-beta-D-xylopyranosyl-(1-->6)-beta-D-glucopyranoside (3), along with three known compounds: junipetriolosides (4), 3,4-dihydroxy-phenyl ethanol (5), and 4-hydroxy-phenyl ethanol (6) were isolated and identified from the n-butanol extract of the roots and rhizomes of Sinopodophyllum emodi (Wall.) Ying. The structures of the above were established by means of spectral data and chemical methods.     

Synthesis and sensory evaluation of all stereoisomers of sedanolide

Synthesis and sensory evaluation of all stereoisomers of sedanolide (1) are described. The asymmetric synthesis was achieved with using the all stereoisomers of bromoalcohol (3) prepared by enzymatic resolution and inversion of the secondary alcohol. All four stereoisomers of 1 were obtained in high enantiomeric purities (>99% ee). Their sensory evaluation revealed that there were distinct differences among the stereoisomers.     

Two new 2'-oxygenated flavones from Andrographis elongata.

Two new 2'-oxygenated flavones, 5,2',6'-trihydroxy-7-methoxyflavone (3) and skullcapflavone I 2'-O-beta-D-(4"-E-cinnamyl) glucopyranoside (5), together with three known flavones, 7-O-methylwogonin (1), skullcapflavone I (2) and skullcapflavone I 2'-O-beta-D-glucopyranoside (4) were isolated from the whole plant of Andrographis elongata, and the structures were elucidated by FAB-MS and one- and two-dimensional (1D- and 2D)-NMR spectral studies including 1H-1H correlation spectroscopy (COSY), heteronuclear single quantum coherence (HSQC), heteronuclear multiple bond connectivity (HMBC) and rotating frame Overhauser enhancement spectroscopy (ROESY) experiments, and chemical studies.     

Stilbene and 2-arylbenzofuran glucosides from the rhizomes of Schoenocaulon officinale

Two stilbene glucosides, oxyresveratrol 2-O-beta-glucopyranoside and resveratrol 3,4'-O,O'-di-beta-D-glucopyranoside, and a 2-arylbenzofuran glucoside, schoenoside, were isolated from the rhizomes of Schoenocaulon officinale, along with five known compounds, oxyresveratrol 3'-O-beta-D-glucopyranoside, oxyresveratrol, resveratrol 3-O-beta-D-glucopyranoside, mulberroside A and moracin M 3'-O-beta-D-glucopyranoside. The structural elucidations were based on analyses of both physical and spectroscopic data.     

Enantiomer Separation of the Four Stereoisomers of 1-(4-Hydroxy-3-Methoxy)-Phenyl-2-[4-(1,2,3-Trihydroxy-Propyl)-2-Methoxy]-Phenoxy-1,3-Propandiol from Hydnocarpus annamensis by Capillary Zone Electrophoresis with HP-β-CD as Chiral Selector

A capillary zone electrophoresis method with HP-β-CD as chiral selector was established for the chiral separation of four stereoisomers of 1-(4-hydroxy-3-methoxy)-phenyl-2-[4-(1,2,3-trihydroxy-propyl)-2-methoxy]-phenoxy-1,3-propandiol for the first time, which were isolated from Hydnocarpus annamensis. The effects of chiral selector type and concentration, buffer composition, pH and concentration, and cartridge temperature on the enantioseparation were investigated. A baseline separation of the four stereoisomers was achieved in less than 18 min under the optimized conditions: 40 mmol L⁻¹ Borax–NaOH buffer (pH 10.02) in the presence of 100 mmol L⁻¹ HP-β-CD at 15°C and 30 kV. The experimental results showed that the method by capillary zone electrophoresis for the separation of four stereoisomers is powerful, sensitive and fast, requires less amounts of reagents, and can be employed as a reliable alternative to other methods.     

Diastereomeric resolution of nucleoside analogues, new potential antiviral agents, using high-performance liquid chromatography on polysaccharide-type chiral stationary phases

This paper describes the separation of the four sets of stereoisomers of nucleoside analogs, new potential antiviral agents by direct analytical HPLC methods using derivatized cellulose and amylose chiral stationary phases. The resolution was made using normal-phase methodology with a mobile phase consisting of n-hexane-alcohol (ethanol or 2-propanol) in various percentages, and a silica-based cellulose tris-3,5-dimethylphenylcarbamate (Chiralcel OD-H), or tris-methylbenzoate (Chiralcel OJ) and a silica-based amylose tris-3,5-dimethylphenylcarbamate (Chiralpak AD) or tris-(S)-1-phenylethylcarbamate (Chiralpak AS). The effects of structural features on the extent of discrimination between the stereoisomers were examined through the retention, the selectivity and the resolution factors as well as the elution order. Baseline separation (Rs>1.5) was easily obtained in many cases. The resolution results were complementary between the different columns.     

Estimation of the pH-independent binding constants of alanylphenylalanine and leucylphenylalanine stereoisomers with beta-cyclodextrin in the presence of urea

The separation of stereoisomers, particularly enantiomers, is important when their physiological activity differs. We have resolved the four stereoisomers each of alanylphenylalanine (Ala-Phe) and of leucylphenylalanine (Leu-Phe) by capillary electrophoresis using beta-cyclodextrin as a buffer additive and urea to enhance its solubility. A study of the influence of pH and beta-cyclodextrin concentration on the separations showed that weak inclusion complexes were formed between the dipeptides and chiral selector. It was found that pH could alter the migration order of enantiomers L-Ala-L-Phe and D-Ala-D-Phe, as well as L-Leu-L-Phe and D-Leu-D-Phe; however, there was no change in order for the other pairs of optical isomers. Electrophoretic mobility data were used to estimate the acid dissociation constants of the dipeptide isomers at pH < 7 with no chiral selector present. By varying the concentration of beta-cyclodextrin, the chiral selector, the binding constants of Ala-Phe and Leu-Phe optical isomers in their fully protonated and zwitterionic forms were estimated. For the four Ala-Phe stereoisomers, K = 42-66 M(-1) and 4-41 M(-1) for the cationic and zwitterionic forms, respectively. For the four Leu-Phe stereoisomers, K = 43-94 M(-1) and 1-28 M(-1) for the cationic and zwitterionic forms, respectively.     

Synthesis of farnesol isomers via a modified Wittig procedure

[structure: see text] The four olefin stereoisomers of farnesol have been synthesized from readily available nerylacetone or commercial geranylacetone. A new variation on the use of beta-oxido ylides favored the (2Z)-stereoisomers, whereas the (2E)-isomers were obtained through a classical Horner-Wadsworth-Emmons condensation with triethyl phosphonoacetate and reduction of the resulting ester.     

Saracoside: a new lignan glycoside from Saraca indica, a potential inhibitor of DNA topoisomerase IB

Chemical investigation of the stem bark of Saraca indica has resulted in the isolation of a new lignan glycoside, saracoside, along with four known lignan glycosides lyoniside, icariside E3, (+)5'-methoxyisolarciresinol-9'-O-beta-D-glucopyranoside and nudiposide, and a phenolic glucopyranoside, 3,4,5-trimethoxyphenyl-beta-D-glucopyranoside, which has been isolated for the first time from this species. The isolated lignan glycosides exhibit potent DNA topoisomerase IB inhibitory activity.     

Divergent syntheses of all 16 carbasugar stereoisomers via stereoconversion of carba-β-d-altropyranose derivatives

We have developed practical synthetic routes to enantiopure d- and l-carba-β-altrose derivatives and all the possible stereoisomers via their divergent stereoconversions. Carba-β-d-altrose was prepared from 3-cyclohexene-1-carboxylic acid and converted to carba-β-d-mannose, carba-β-d-idose, and carba-β-d-talose derivatives via regio- and stereoselective oxidation/reduction of 3-OH and/or 4-OH. The four carbasugar stereoisomers were then transformed to the remaining 12 carbasugar stereoisomers and their 1,2-epoxides by regio- and stereoselective manipulation of hydroxyl groups in C1 and C2, which includes oxidation/reduction, Mitsunobu’s reaction, olefination/dihydroxylation, and epoxidation/ring-opening protocols.     

Anti-oxidative activity of glycosides from Ligustrum sinense

Three active glycosides that afford protection to red blood cell membrane to resist hemolysis induced by a peroxyl radical initiator, 2,2'-azo-bis-(2-amidinopropane) dihydrochloride (AAPH) were isolated from the MeOH extract of Ligustrum sinense. The compounds are 10-hydroxyl-oleuropein (1), 3-O-alpha-L-rhamnopyranosyl-kaempferol-7-O-beta-D-glucopyranoside (4), and 8'-alpha-hydroxyl-lariciresinol-4'-O-beta-D-glucopyranoside (6). The structures of these glycosides were determined by 1D and 2D NMR spectral analysis.