Helferich Method Research Articles

Palladium-Catalyzed O - and N -Glycosylation with Glycosyl Chlorides

Despite the significant progress in carbohydrate chemistry, there remains a pressing need for efficient and practical glycosylation methods using simple glycosyl donors and with high atom economy. ...

Water Solubility and Surface Property of Alkyl Di-/Tri-/Tetraoxyethyl β-d-Xylopyranosides.

Alkyl di-/tri-/tetraoxyethyl β-d-xylopyranosides as derivatives of alkyl xylosides are a class of non-ionic sugar-based surfactants. They were stereoselectively synthesized by the Helferich method. Their properties including hydrophilic-lipophilic balance number, water solubility, surface property, foam property, emulsifying property, and thermotropic liquid crystal property were mainly investigated. The results showed that their water solubility decreased with increasing the alkyl chain length and increasing the number of the oligooxyethyl fragment. The critical micelle concentration had a monotonous decreasing trend with increasing the alkyl chain length. Nonyl di-/tri-/tetraoxyethyl β-d-xylopyranosides [-(OCH2CH2)m-, where m = 2, 3, and 4] exhibited the most excellent foaming ability and foam stability. In the n-octane/water system, dodecyl tetraoxyethyl β-d-xylopyranosides and tetradecyl tetraoxyethyl β-d-xylopyranosides had the strongest emulsion ability. In addition, some alkyl di-/tri-/tetraoxyethyl β-d-xylopyranosides had thermotropic liquid crystal properties. Such sugar-based surfactants, alkyl di-/tri-/tetraoxyethyl β-d-xylopyranosides, will be expected to develop for a variety of practical application.

Synthesis and surface properties of alkyl β‑d‑thioglucopyranoside

Alkyl thioglycosides are a class of nonionic sugar-based sulfur-containing surfactants and bioreagents. The surfactants 1,2‑trans alkyl β‑d‑thioglucopyranosides with different alkyl chain length (n = 6–12) were stereoselectively prepared by the Helferich method. Their properties including HLB number, logP value, water solubility, foam property, emulsifying property, surface property and thermotropic liquid crystal property were mainly investigated. The results showed that their HLB numbers and water-solubility decreased as the related logP values increased with increasing the alkyl chain length. Alkyl β‑d‑thioglucosides were already insoluble in water with n ≥ 10. Both β‑d‑thioglucopyranosides (n = 8, 9) reduced the surface tension of the related aqueous solution to nearly 29 mN·m−1 at the critical micelle concentration (CMC), they also had excellent foaming ability and foam stability. Nonyl β‑d‑thioglucopyranoside had good emulsifying properties for both n‑octane/water system and toluene/water system. Alkyl β‑d‑thioglucopyranosides (n = 6–12) were observed to have the thermotropic liquid crystal properties.

An Improved Helferich Method for the α/β-Stereoselective Synthesis of 4-Methylumbelliferyl Glycosides for the Detection of Microorganisms.

An improved Helferich method is presented. It involves the glycosylation of 4-methyl-umbelliferone with glycosyl acetates in the presence of boron trifluoride etherate combined with triethylamine, pyridine, or 4-dimethylaminopyridine under mild conditions, followed by deprotection to give fluorogenic 4-methylumbelliferyl glycoside substrates. Due to the use of base, the glycosylation reaction proceeds more easily, is uncommonly α- or β-stereoselective, and affords the corresponding products in moderate to excellent yields (51%–94%) under appropriate conditions.

Glycosylation of Shikonin by the Helferich method

New lipidand water-soluble derivatives were prepared by glucosylation of natural 1 by the Helferich method. A mixture of 1 (288 mg, 1.0 mmol), Hg(CN)2 (252 mg, 1.0 mmol), and molecular sieves 4A (1.0 g) in anhydrous nitromethane (20 mL) was refluxed for 1.5 h, treated with α-acetobromoglucose (820 mg, 2.0 mmol), and cooled. The precipitate was filtered off. The filtrate was evaporated. The solid was chromatographed over SiO2 (40-63 μ) using hexane:acetone (10:1→2:1) to isolate 2 (78 mg, 12%) and 3 (346 mg, 56%). Saponification of 3 (MeONa/MeOH) under an Ar atmosphere followed by chromatography under the same conditions gave 4 (75%). 2-[1′(R)-(Tetra-O-acetyl-α-D-glucopyranosyloxy)-4′-methylpent-3′-en-1′-yl)]-5,8-dihydroxy-1,4-naphthoquinone (2). mp 97-99°C (hexane:acetone). PMR spectrum (300 MHz, CDCl3, δ, ppm, J/Hz): 1.72 and 1.74 (2 × Me), 2.04, 2.06, 2.12, and 2.21 (4 × OAc), 2.42 (2H, m, 2H-2′), 4.08 (1H, dd, J5′′,6′′ = 3.7, J6′′,6′′ = 13.7, H-6′′), 4.28 (2H, m, 1H-5′′, 1H-6′′), 4.84 (1H, d, J1′′,2′′ = 3.7, H-1′′), 4.92 (1H, dd, J2′′,3′′ = 10.3, H-2′′), 5.04 (1H, m, H-3′), 5.09 (1H, dd, J3′′,4′′ = 9.6, J4′′,5′′ = 9.6, H-4′′), 5.29 (1H, m, H-1′), 5.56 (1H, dd, H-3′′), 7.16 (2H, s, arom.), 7.25 (1H, s, arom.), 12.41 and 12.57 (2 × 1H, s, C5-OH or C8-OH). IR spectrum (CHCl3, ν, cm −1): 1752 (CH3COO), 1610 (C=O), 1570, 1455, 1433, 1345, 1247, 1038. 2-[1′(R)-(Tetra-O-acetyl-β-D-glucopyranosyloxy)-4′-methylpent-3′-en-1′-yl)]-5,8-dihydryxo-1,4-naphthoquinone (3). mp 140-141°C (hexane:acetone). PMR spectrum (250 MHz, CDCl3, δ, ppm, J/Hz): 1.56 and 1.59 (2 × Me), 1.92, 2.01, 2.02, and 2.08 (4 × OAc), 2.34 (1H, ddd, J1′,2α′ = 7.5, J2α′,2β′ = 14, J2α′,3′ = 4, H-2α′), 2.52 (1H, ddd, J1′,2β′ = 4, J2β′,3′ = 7.5, H-2β′), 3.61 (1H, ddd, J4′′,5′′ = 9.5, J5′′,6α′′ = 2.5, J5′′,6β′′ = 4.5, H-5′′), 3.98 (1H, dd, J6α′′,6β′′ = 12.0, H-6α′′), 4.06 (1H, dd, H-6β′′), 4.66 (1H, d, J1′′,2′′ = 7.5, H-1′′), 4.94 (1H, dd, H-3′), 5.04 (1H, dd, J3′′,4′′ = 9.0, H-4′′), 5.06 (1H, dd, J2′′,3′′ = 9.5, H-2′′), 5.12 (1H, m, H-1′), 5.21 (1H, t, H-3′′), 7.17, 7.20, and 7.22 (3 × 1H, s, arom.), 12.50 and 12.58 (2 × 1H, s, C5-OH or C8-OH). IR spectrum (CHCl3, ν, cm −1): 1757 (CH3COO), 1609 (C=O), 1570, 1455, 1435, 1410, 1367, 1249, 1065, 1040. 2-[1′(R)-(β-D-Glucopyranosyloxy)-4′-methylpent-3′-en-1′-yl)]-5,8-dihydroxy-1,4-naphthoquinone (4). mp 193195°C (hexane:acetone). PMR spectrum (300 MHz, DMSO-d6, δ, ppm, J/Hz): 1.44 and 1.60 (2 × Me), 2.37 (1H, m, H-2α′), 2.58 (1H, m, H-2β′), 3.06 (3H, m, H-2′′, H-3′′, H-5′′), 3.15 (1H, m, H-4′′), 3.35 (1H, m, H-6α′′), 3.53 (1H, m, H-6β′′), 4.31 (1H, br.t, J = 5.7, C6′H-OH), 4.36 (1H, d, J1′′,2′′ = 7.7, H-1′′), 4.89 (1H, br.s, C-OH), 4.96 (1H, br.s, C-OH), 5.01 (1H, m, H-3′), 5.12 (1H, br.s, C-OH), 5.23 (1H, m, H-1′), 7.16 (1H, s, arom.), 7.35 (2H, s, arom.), 12.32 and 12.37 (2 × 1H, s, C5-OH or C8-OH). IR spectrum (KBr, ν, cm−1): 3418 (OH), 1633 (C=O), 1616 (C=O), 1456, 1384, 1348, 1273, 1200, 1159, 1073, 1033.

Decomposition of α-Tocopheryl Glycosides in Rat Tissues

ABSTRACTBackground: The aim of our investigation was to estimate the stability of α-tocopheryl O-glycosides in relation to activity of exoglycosidases in selected rat tissues. Material and Methods: Acetylated glycosides were obtained in glucosidation of α-tocopherol using the Helferich method. The activity of exoglycosidases was determined by the Zwierz et al. method. Protein concentrations were determined by the biuret method. The concentration of released α-tocopherol was determined with the HPLC method. Results: The comparison of the amount of released α-tocopherol with the amount of released p-nitrophenol shows that glycoside bound in 2a–5a derivatives of α-tocopherol undergoes hydrolysis significantly harder than in appropriate 2b–5b p-nitrophenyl derivatives. Conclusion: The results indicate that tocopheryl O-glycosides are more resistant to enzymatic hydrolysis than appropriate p-nitrophenol O-glycosides 2a–5a. Among examined tocopheryl O-glycosides, galactoside 4 is the only compound that caused the significant increase in tocopherol concentration, as compared to its endogenic content.

Synthesis of α-Tocopheryl Glycosides

Abstract An unusual course of d-α-tocopherol glucosylation by the Helferich method was observed. The product distribution very depended on acid catalyst and solvent used. The β-glucoside was accompanied by an unsaturated α-glucoside. Other unsaturated d-α-tocopheryl glucosides were obtained by reactions with acetylated glucal and 2-acetoxy glucal.

Synthesis of α-D-Glucopyranosyl-(1-3)-α-D-Mannopyranosyl-(1-7)-4-Methylumbelliferone, A Fluorogenic Substrate for Endo-α-1,2-Mannosidase

ABSTRACT α-D-Glucopyranosyl-(1-3)-α-D-mannopyranosyl-(1-7)-4-methylumbelliferone (Glc-Man-Muf) was synthesized as a potential fluorogenic substrate for endo-α-1,2-mannosidase. The synthesis was designed in a convergent way. The glucose donor ethyl 2,3,4,6-tetra-O-benzyl-1-thio-β-glucopyranoside and the mannose acceptor 1,2:4,6-di-O-isopropylidene-ß-D-mannopyranose were coupled in the presence of N-iodosuccinimide and trifluoromethane-sulfonic acid to yield the corresponding disaccharide derivative. After conversion into peracetylated α-D-glucopyranosyl-(1-3)-α-D-mannopyranose the disaccharide was attached to 4-methylumbelliferone using the Helferich method. After separation of the desired isomer, deacetylation yielded the title compound. Glc-Man-Muf was used as a substrate in endomannosidase assays with rat liver Golgi preparations as an enzyme source (in the presence of the α-glucosidase inhibitor deoxynojirimycin). The degradation of Glc-Man-Muf was linear with protein up to 300 μg and with time up to 2 h. Vmax and Km were determined to be 0.17 nmol/mg x h and 3.7 mM, respectively.

Artificial deoxy glycosides of anthracyclines

AbstractIn Lewis acid mediated allylic rearrangement reactions of L‐rhamnal (1) and L‐fucal (2) with daunomycinon (6) 2′‐deoxyhex‐2′‐enopyranosides have been obtained exclusively. Furthermore, glycals 1 and 4 have been treated with the glycosyl acceptors 6, 7, and 9 and N‐iodosuccinimide (NIS) to produce the corresponding α‐configurated 2′‐deoxy‐2′‐iodo glycosides. Among these, 16 represents a bis (glycoside) with both benzylic aglycon positions substituted. In none of the above cases has a substantial amount of β‐glycoside been detected. Attempts to convert ε‐isorhodomycinon (8) into a glycoside on a preparative scale, under Lewis acid conditions have been unsuccessful. However, the α‐glycoside 13 has been obtained by the Helferich method.

Glycosylation of 20(S),24(R)-epoxydammarane-3α,12β,25-triol in the presence of insoluble silver compounds

The glycosylation of 20(S),24(R)-epoxydammarane-3α,12β,25-triol (betulafolienetriol oxide; BFTO) in the presence of silver oxide and a silver zeolite has been studied. It has been established that in contrast to the glycosylation of BFTO in nitromethane in the presence of mercuric bromide (orthoester method) and the Helferich method, glycosylation in the presence of insoluble silver catalysts takes place nonregioselectively and leads to the formation of a mixture of glucoside acetates.

Preparation of p-mitrophenyl .BETA.-D-mannopyranoside by the helferich method and separation of some anomeric p-nitro-phenyl aldopyranoside acetates using thin-layer chromatography.

Preparation of p-mitrophenyl .BETA.-D-mannopyranoside by the helferich method and separation of some anomeric p-nitro-phenyl aldopyranoside acetates using thin-layer chromatography.

Studies on glycosylation. II. A S-glycosylation by use of stannic chloride.

Application of the Helferich method to the preparation of thioglycosides was performed in dichloroethane at room temperature by use of SnCl4 as catalyst. The reaction gave 1-thio-β-D-glucopyranoside from penta-O-acetyl-β-D-glucopyranose and thiophenol in good yield. However, the similar reaction with methyl 1, 2, 3, 4-tetra-O-acetyl-β-D-glucopyranuronate and thiophenol gave an unpredicted product, 3, 4-di-O-acetyl-6-methoxy 6-thiophenyl-α-D-glucopyranose 1, 2-(phenylthio orthoacetate). The structure was confirmed by analytical and spectral data.

Aryl glycosides of oligosaccharides : part I. p-bromophenyl β-glycosides of cellobiose, lactose, and maltose

The p-bromophenyl β-glycosides of cellobiose, lactose, and maltose have been prepared via their hepta- O-acetyl derivatives, by an adaptation of Griebel and Helferich's method 1 for the preparation of phenyl β-lactoside. In preliminary experiments, it was found that this version of the Koenigs-Knorr reaction gave better results in the synthesis of aryl glycosides of disaccharides than the method outlined by Rosenmund and Güssow 2 for the synthesis of aryl glycosides of monosaccharides

グルクロン酸とグルコースとのα (1, 4) 重合体に関する研究 (第2報)

The reaction of 1 mole of maltose and 3.6 moles of trityl chloride in pyridine followed by acetylation afforded 6′-tritylheptaacetylmaltose (IV), m. p. 162-163°, and 6, 6′-ditritylhexaacetylmaltose (V), m. p. 215-217°. Deacetylation of IV and V respectively afforded 6′-tritylmaltose (VI), m. p. 137-139°, and 6, 6′-ditritylmaltose (VII), m. p. 149-152°. The structure of these compounds was determined from their analytical values, their infrared spectra, and confirmation of methylglucoses obtained by methylation of VI and VII, followed by acid hydrolysis. The ditritylmaltose, m. p. 137-139°, and ditritylhexaacetylmaltose, m. p. 116-119°, reported by Josephson are not a unity and were proved by the present work to be a mixture, respectively, of VI and VII, and of IV and V.The use of a large excess of trityl chloride in tritylation of I results in by-product formation of VI and VII alone is not obtained, indicating that the two primary alcohols in I behave differently. Detritylation of IV and V respectively gave heptaacetylmaltose (XI) and hexaacetylmaltose (XII). It was found that Helferich's method cannot be used in the case of V since this method results in the by-product formation of acetobromo compound.

配糖体合成の研究 (第4報)

In the synthesis of phenolic glycosides, the yield of the α- and β-types of tetraacetylphenyl-D-glucoside by the Helferich method, with zinc chloride as a catalyst, is very poor. In order to increase the yield of the α-compound, over ten kinds of compounds were used in place of zinc chloride and it was found that zinc bromide gave a far better yield of the α-compound. In the screening of these catalysts, it was found that the mixing ratio of the α- and β-types in the crude tetraacetylphenyl-D-glucoside obtained by the condensation could be calculated by the use of a graph showing the specific rotation and mixing ratio of various mixtures of pure tetraacetyl-α, β-phenyl-D-glucoside.

澱粉糖の不醗酵成分について (第2報)

Gentiobiose was quantitatively determined by the increase of its reductive power by the hydrolysis of gentiobiose by Takadiastase. Gentiobiose was determined in a similar manner in the non-fermenting sugars formed from glucose. By the use of Somogyi's microanalytical method for sugar determination, only about 2mg. of sample is necessary. Following observations were also obtained:1) The reductive power of gentiobiose against Somogyi's reagent corresponds to 0.542 of glucose.2) The hydrolysis rate of commercial Takadiastase against gentiobiose is about 10 times faster than the hydrolysis rate of the standard emulsin prepared from almond seeds by the Helferich method (omitting purification by silver oxide).