Practical Preparation of Resveratrol 3-O-β-D-Glucuronide

Abstract

A practical synthesis of resveratrol 3-O-β-D-glucuronide, suitable for preparation of large quantities, was developed using selective deacetylation of resveratrol triacetate with ammonium acetate. A simplified procedure for large-scale preparation of resveratrol is also reported.     

Synthesis of Quercetin 3-O-[6″-O-(trans-p-Coumaroyl)]-β-D-Glucopyranoside

This report describes the efficient synthesis of quercetin 3-O-[6^″-O-(trans-p-coumaroyl)]-β-D-glucopyranoside 1 (isoquercitrin coumarate), an acylated quercetin glycoside possessing antihypertensive, antidiabetic, and tyrosinase inhibitory activities. The synthesis is initiated from commercially available quercetin via regioselective benzylation of quercetin to produce 4′, 7-di-O-benzylquercetin (4). Through 4, 1 was successfully achieved via selective β-glycosylation of the 3-OH, acylation of 6^″-OH, and finally debenzylation via catalytic transfer hydrogenation.     

Syntheses of Methyl 2-O-, 3-O- and 6-O-(2′-Hydroxypropyl)-α-D-Glucopyranosides 1

Abstract

Methyl 6-O-, 3-O- and 2-O-(2′-hydroxypropyl)-α-D-glucopyranosides (4,8, and 12) were synthesized starting from methyl 2,3,4-tri-O-benzyl-α-D-glucopyranoside (1), methyl 4,6-O-benzylidene-α-D-glucopyranoside (5), and methyl 3-O-benzyl-4,6-O-benzylidene-D-glucopyranoside (9), respectively. Overall yields were 88%, 6% and 26% of 4, 8 and 12, respectively, with the 2-ether (12) being crystalline and the 3-ether (8) a single diastereomer.

     

Synthesis of Methyl 2-O-, 3-O-, 4-O-, 6-O-, 2,3-Di-O- and 4,6-Di-O-β-D-Galactopyranosyl-β-D-glucopyranoside

Abstract

Synthesis of methyl O-β-D-galactopyranosyl-(1→2)-β-D-glucopyranoside 1, methyl O-β-D-galactopyranosyl-(1→3)-β-D-glucopyranoside 2, methyl O-β-D-galactopyranosyl-(1→4)-β-D-glucopyranoside 3, methyl O-β-D-galactopyranosyl-(1→6)-β-D-glucopyranoside 4, methyl O-β-D-galactopyranosyl-(1→4)-[O-β-D-galactopyranosyl-(1→6)]-β-D-glucopyranoside 5, and methyl O-β-D-galactopyranosyl-(1→2)-[O-β-D-galactopyranosyl-(1→3)]-β-D-glucopyranoside 6, using 2,3,4,6 tetra-O-acetyl-α-D-galactopyranosyl trichloroacetimidate or 2,3,4,6 tetra-O-acetyl-α-D-galactopyranosyl bromide as a glycosyl donor and selectively protected derivatives of methyl O-β-D-glucopyranoside as glycosyl acceptors are described.     

Improvement of Regio-Specific Production of Myricetin-3-O-α-l-Rhamnoside in Engineered Escherichia coli

Myricetin is an important flavonol whose medically important properties include activities as an antioxidant, anticarcinogen, and antimutagen. The solubility, stability, and other biological properties of the compounds can be enhanced by conjugating aglycon with sugar moieties. The type of sugar moiety also plays a significant role in the biological and physical properties of the natural product glycosides. Reconstructed Escherichia coli containing thymidine diphosphate-α-l-rhamnose sugar gene cassette and Arabidopsis-derived glycosyltransferase were used for rhamnosylation of myricetin. Myricetin (100 μM) was exogenously supplemented to induced cultures of engineered E. coli. The formation of target product—myricetin-3-O-α-l-rhamnoside—was confirmed by chromatographic and NMR analyses. The yield of product was improved by using various mutants and methylated cyclodextrin as a molecular carrier for myricetin in combination with E. coli M3G3. The maximal yield of product is 55.6 μM (3.31-fold higher than the control E. coli MG3) and shows 55.6 % bioconversion of substrate under optimized conditions.     

3-O-甲基槲皮素的合成

以芦丁为原料经苄基化、酸水解、选择性甲基化和氢化脱苄四步反应,合成了3-O-甲基槲皮素,总收率为76%.利用1H NMR和MS对中间体及产物的结构进行了确证.该发现有望为3-取代槲皮素衍生物的合成提供一条捷径.     

Synthetic Mucin Fragments: Methyl-3-O-(2-Acetamido-2-Deoxy-4-O- and 6-O-β-D-Galactopyranosyl-β-D-Glucopyranosyl)-β-D-Galactopyranoside and Methyl 3-O-(2-Acetamido-2-Deoxy-4-O- and 3-O-Methyl-β-D-Glucopyranosyl-3-D-Galactopyranoside

Abstract

Glycosylation of methyl 3-O-(2-acetamido-3, 6-di-O-benzyl-2-deoxy-β-D-glucopyranosyl)-2,4,6-tri-O-benzyl-β-D-galactopyranoside (2) with 2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl bromide (1), catalyzed by mercuric cyanide, afforded a trisaccharide derivative, which was not separated, but directly O-deacetylated to give methyl 3-O-(2-acetamido-3,6-di-O-benzyl-2-deoxy-4-O-β-D-galactopyranosyl-β-D-giucopyranosyl)-2,4,6-tri-O-benzyl-β-D-galactopyranoside (8). Hydrogenolysls of the benzyl groups of 8 then furnished the title trisaccharide (9). A similar pflyccsylation of methyl 3-O-(2-acetamido-3-O-acetyl-2-deoxy-β-D-glucopyranosyl)-2,4,6-tri-O-benzyl- β-D-galactopyranoside (obtained by acetylation of 4, followed by hydrolysis of the benzylidene acetal group) with bromide 1 gave a tribenzyl trisaccharide, which, on catalytic hydrogenolysls, furnished the isomeric trisaccharide (12). Methylation of 4 and 2 with methyl iodide-silver oxide in 1:1 dichloro-methane-N, N-dimethylformamide gave the 3-O- and 4-O-monomethyl ethers (13) and (15), respectively. Hydrogenolysis of the benzyl groups of 13 and 15 then provided the title monomethylated disaechartdes (15) and (16), respectively. The structures of trisacchacides 9 and 12, and disaccharides 14 and 16 were all established by ¹³C MMR spectroscopy.     

Synthesis of Amides of 3-O-Acetyl-18-βH-glycyrrhetic Acid

Methods of preparing amides of 3-O-acetyl-18-H-glycyrrhetic acid from certain amines are described. The structures of the prepared amides have been confirmed by chemical and spectral analyses     

Syntheses of P-Nitrophenyl 6-O-α- and 6-O-β-D-Xylopyranosyl-β-D-glucopyranoside

Condensation of p-nitrophenyl 2,3,4-tri-O-benzoyl-β-D-glucopyranoside 3 with 2,3,4-tri-O-(chlorosulfonyl)-β-D-xylopyranosyl chloride by the Koenigs-Knorr method afforded the α-linked product in a high yield. Dechlorosulfation with sodium iodide and debenzoylation by the Zemplen method gave crystalline p-nitrophenyl 6-O-(α-D-xylopyranosyl)-β-D-glucopyranoside 7.

Compound 3 was condensed with 2,3,4-tri-O-benzoyl-α-D-xylopyranosyl bromide in the presence of mercury (II) cyanide in acetonitrile, and after debenzoylation, crystalline p-nitrophenyl 6-O-(β-D-xylopyranosyl)-β-D-glucopyranoside 10 was obtained.     

Differentiation of 2′-O- and 3′-O-methylated Ribonucleosides by tandem mass spectrometry

Recent studies revealed that the 3'-terminal nucleotides in plant microRNAs were methylated on the ribose at the 2' or 3' hydroxyl groups. Here we examined the fragmentation of the electrospray-produced [M + H]+ and [M - H]- ions of 2'- and 3'-O-methylated ribonucleosides. It turned out that the predominant fragmentation pathway for the [M + H]+ ions of ribose-methylated nucleosides was the neutral loss of the methylated ribose, which made it impossible to distinguish 2'-O-methylation from 3'-O-methylation by positive-ion MS/MS. However, characteristic fragment ions, resulting from the cleavage through the ribose rings, were produced for the [M - H]- ions of each pair of ribose-methylated nucleosides. In this respect, the neutral loss of a 90-Da fragment (C3H6O3) was observed for 2'-O-methylated cytidine, guanosine and adenosine, but not for their 3'-O-methylated counterparts. On the other hand, the neutral loss of a 60-Da fragment (C2H4O2) was found for 3'-O-methyluridine, but not for 2'-O-methyluridine.     

Fluoro-Hydroxylation of gem-Difluoroalkenes:Synthesis of 18O-labeled α-CF3 Alcohols

in this paper,a fluoro-hydroxylation of gem-difluoroalkenes is demonstrated.This protocol uses sequential electrophilic fluorination with Selectfluor and nucleophilic hydroxylation with H218o,which can be used to prepare 18Oo-labeled α-CF3 alcohols from gem-difluorostyrenes.The reaction is typically carried out at room temperature within 4h in good to excellent yields.Other nucleophiles (besides H218o),such as alcohols,carboxylic acid, acetonitrile and N,N-dimethylformamide,are also suitable for this difunctionalization of gem-difluoroalkenes.     

Synthesis of 4-O-(α-L-Rhamnopyranosyl-D-Glucopyranuronic Acid

Abstract

Two approaches were used for the synthesis of 4-O-(α-l-rhamno-pyranosyl)-d-glucopyranuronic acid (1). Rhamnosylation of benzyl 6-O-allyl-2,3-di-O-benzyl-β-d-glucopyranoside (7), followed by deallylation, oxidation to uronic acid, and deblocking afforded 1. Alternatively, rhamnosylation of suitably protected d-glucuronic acid derivatives (25 and 26) gave the protected pseudoaldoBiouronic acid derivatives (19 and 30), which were deprotected. Rhamnosylations were performed in high stereoselectivity without neighbouring-group assistance using 2,3,4-tri-O-benzyl-1-O-trichloroacetimidoyl-α-l-rharnnopyranose (27) with tri-fluoromethanesulfonic acid catalysis.     

Synthesis and investigation of antiviral activity of 3′-O-(aminoalkyl)-thymidines and their quaternary ammonium salts

Summary Alkylation of 5-O-tritylthymidine with dialkylaminoalkyl chlorides in the presence of sodium hydride yields 3-O-dialkylaminoalkyl-5-O-tritylthymidine derivatives2 which were treated with an excess of iodomethane to afford the corresponding quaternary ammonium derivatives3. Deprotected nucleosides4 and6 were obtained by refluxing3 and2, respectively, in 80% acetic acid. When the compounds2–4 and6 were investigated for activity against HSV and HIV, the trityl derivatives2a and2c were found active against HSV.

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Synthese und Untersuchung der antiviralen Aktivität von 3-O-(Aminoalkyl)-thymidinen und ihrer quartären Ammoniumsalze

Zusammenfassung Alkylierung von 5-O-Tritylthymidin mit Dialkylaminoalkylchloriden in Gegenwart von Natriumhydrid ergab 3-O-Dialkylaminoalkyl-5-O-tritylthymidinderivate2, die mit einem Überschuß an Iodmethan zu den entsprechenden quartären Ammoniumderivaten3 umgesetzt wurden. Die entschützten Nucleoside4 und6 wurden durch Kochen von3 bzw.2 in 80% iger Essigsäure unter Rückfluß erhalten. Bei der Untersuchung von2–4 und6 im Hinblick auf ihre Wirksamkeit gegen HSV und HIV wurde bei den Tritylderivaten2a und2c Aktivität gegen HSV festgestellt.

     

Synthesis of 7-O-β-D-glucopyranosides of isoflavones and their heterocyclic analogues

The products of the interaction of -acetobromoglucose with 2,4,5-trihydroxyphenyl benzyl ketone and 2,4-dihydroxyphenyl 4-hydroxybenzyl ketone and also with their heterocyclic analogues, which are present completely or partially in the enolic form, have been investigated. It has been shown that in this reaction a tetra-O-acetylglucosyl residue is added at the 4-OH hydroxy group of the phenyl residue of the ketone. The compounds obtained have been converted into isoflavone 7-O-glucosides by the action of the vilsmeier reagent or acetoformic anhydride.Taras Shevchenko Kiev University. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 220–227, March–April, 1993.     

3-O-乙酰基-4,6-二-O-苄基-1,2-环丙烷葡萄糖的合成

以葡萄糖为起始原料制得苄基葡萄烯糖,再经Ferrier重排、双羟化反应、选择性磺酰化、羟基保护和在碱性条件下关环反应合成了3-O-乙酰基-4,6-二-O-苄基-1,2-环丙烷葡萄糖.其中5个中间体为新化合物,其结构经1H NMR,13C NMR和HR-MS表征.     

2′-O-乙酰基-3-酮基-10,11-脱水-12-O-咪唑酰基-6-O-甲基红霉素的合成

以2′-O-乙酰基-3-羟基-11,12-环碳酸酯-6-O-甲基红霉素为原料,通过DMSO/P2O5氧化其3-羟基;再以六甲基二硅胺基钠为碱,经消除、咪唑酰基化"一锅煮"方法合成了抗生素泰利霉素的关键中间体--2′-O-乙酰基-3-酮基-10,11-脱水-12-O-咪唑酰基-6-O-甲基红霉素,总收率68.3%.     

Synthesis and Biological Evaluation of Analogs of Methyl Ursolate 3-O-β-Chacotrioside as H5N1 Viral Entry Inhibitors

The earliest stage of influenza virus infection is the viral entry to the host cell. In our previous work, we discovered the first three small molecule H5N1 viral entry inhibitors 1–3. Here, based on saponin 3, methyl ursolate 3-O-β-chacotrioside, several analogs were synthesized and evaluated to understand the structure-activity relationships of this type of compound on the H5N1 viral entry inhibitory activity. The preliminary studies demonstrated that unlike saponins 1 and 2, it is possible to reduce the 3-O-chacotriosyl residue of compound 3 to a disaccharide without affecting the viral entry activities significantly. The results obtained will render new clues to the understanding of the antiviral profile for these types of compounds.     

3-羟基-6-O-甲基红霉素的氧化

3-酮基-红霉素化合物是合成酮内酯化合物的关键中间体,由相应的3-羟基红霉素化合物氧化得到.本文对3-羟基-6-O-甲基红霉素(Ⅱ)生成3-酮基化合物(Ⅴ)的氧化反应进行了研究.Ⅱ经乙酰化、碳酸酯化保护后,采用五氧化二磷(P2O5)和乙酸酐(Ac2O)作为活化剂的二甲基亚砜法对其氧化.结果表明,两者在室温下,即能将保护后的Ⅱ转化为目标化合物Ⅴ.Ⅴ的得率分别为85.8%和78.3%.这两种氧化方法成本低、安全性好、环境友好并容易操作,具有规模化生产的前景.     

A Mechanism-based 3D-QSAR and DFT Approach for the Prediction of H5N1 Entry Inhibitory Potency of 3-O-β-chacotriosyl Ursolic Acid Derivatives

In this work, 25 3-O-β-chacotriosyl ursolic acid derivatives were employed to achieve the highly reliable and predictive 3 D-QSAR models by Co MFA and Co MSIA methods, respectively. The predictive capabilities of two constructed CoMFA and CoMSIA models were verified by the leave-one-out cross-validation method. The results showed that the cross-validated coefficient(q2) and non-cross-validated coefficient(R2) were 0.559, 0.981 in the CoMFA model and 0.696, 0.978 in the CoM SIA model, respectively, which suggests that these two models are robust and have good exterior predictive capabilities. Furthermore, based on the contour maps information of two models, ten novel inhibitors with higher inhibitory potency were designed, and the quantum chemical calculation of density functional theory(DFT) was performed to investigate the mechanism why the designed molecules have stronger inhibitory activity than the lead compound. The calculations show that the C-50 position of lead compound is a key active site for the enhancement of inhibitory activity, and it should be introduced into the large electron withdrawing group, which would result in generating potent and selective H5 N1 entry inhibitors. We expect that the results in this paper could provide important information to develop new potent H5 N1 entry inhibitors.     

?-3-O-酰基-2-O-苄基-甘油二烷基磷酸酯的合成和结构表征

?-3-O-酰基-2-O-苄基-甘油二烷基磷酸酯的合成和结构表征; ?-O-酰基-O-苄基-甘油二烷基磷酸酯;磷脂类似物;生物活性物质