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.     

Syntheses of Methyl 2,3-di-O-Glycyl-α-D-glucopyranoside and 4,6-di-O-Glycyl-2,3-di-O-methyl-α-D-glucopyranoside,and Removal of Aminoacyl Groups from Sugar Moieties

Abstract

To confirm the potential usefulness of amino acid residues as protecting groups for sugar hydroxyls, methyl 2,3-di-O-glycyl-α-D-glucopyranoside (5) and methyl 4,6-di-O-glycyl-2,3-di-O-methyl-α-D-gluco-pyranoside (7) were synthesized as reference compounds. Conditions were then established for the removal of these aminoacyl groups from the sugar molecules. The reference compounds were easily prepared by condensation of methyl α-D-glucopyranoside derivatives with N-protected glycine in the presence of dicyclohexyl-carbodiimide (DCC). The aminoacyl groups were removed by alkaline treatment, as were conventional acyl groups and also with ease by enzymatic hydrolysis using Pronase E. Conventional ester and ether protecting groups are not removed by such enzymatic treatment. Removal of aminoacyl group from sugar moieties on a practical scale is also described.     

Syntheses of Pseudo-α-D-Glucopyranose and Pseudo-β-L-Altropyranose From L-Arabinose

Abstract

Two optically active pseudo-hexopyranoses, pesudo-α-D-glucopyranose (1) and pseudo-β-L-altropyranose (2), were synthesized starting from L-arabinose. L-Arabinose was first converted to an acyclic aldehyde 9. The reaction of 9 with dimethyl malonate under basic conditions provided a tetra-hydroxylated cyclohexane-1,1-dicarboxylate 11 and a C-glycoside of β-L-arabinopyranose 12. From the compound 11, the desired two pseudo-sugars were synthesized by 1) thermal demethoxy-carbonylation, 2) LiAlH₄, reduction, 3) hydroboration of the resulting 1-hydroxymethyl-l-cyclohexene 14 followed by hydrogen peroxide treatment, and 4) removal of the protecting groups.     

New insights into the transitional behaviour of methyl-6-O-(n-dodecanoyl)-α-D-glucopyranoside using variable temperature FTIR spectroscopy and X-ray diffraction

The liquid crystalline behaviour of methyl-6-O-(n-dodecanoyl)-α-D-glucopyranoside, 1, has been characterised using X-ray diffraction and variable temperature Fourier transform infrared (FTIR spectroscopy). 1 exhibits a monotropic interdigitated smectic A phase consisting of bilayers in which the alkyl chains are overlapped. The crystal–isotropic transition is accompanied by a pronounced decrease in the strength of the hydrogen bonding network involving the sugar groups resulting in a marked change in the environment of the alkyl chains. The isotropic phase consists of disordered smectic-like domains stabilised via hydrogen bonding between the sugar groups. At the transition to the smectic A phase, a subtle change in hydrogen bonding is observed which is manifested by a change in the temperature dependence of the OH stretching peak position in the FTIR spectrum. On crystallisation, the strong hydrogen bonding network is re-established accompanied by a change in the conformational distribution of the alkyl chains. A model is proposed in which a combination of hydrogen bonding (enthalpic effects) and conformational arrangements (entropic effects) promotes initially the formation of smectic-like domains in the isotropic phase and subsequently stabilises the smectic A phase by inhibiting the microphase separation leading to the crystal phase.     

Stereospecific total syntheses of 7α- and 7β-eremophilane-6-one and 7α- and 7β-eremophilane

The title compounds have been prepared in a highly efficient fashion by a synthetic route involving an intramolecular Diels-Alder reaction of an acetylenic thiazole followed by reductive modification of the resulting fused-ring thiophene.     

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.     

Derivatives Of α-Cyclodextrin and the Synthesis of 6-O-α-D-Glucopyranosyl-α-Cyclodextrin

Abstract

Regioselective silylation of α-cyclodextrin with tert-butyl-dimethylsilyl chloride in N, N-dimethylformamide in the presence of imidazole gave, in 75% yield, the hexakis(6-O-tert-butyldimethylsilyl) derivative 2, which was transformed into the hexakis(2,3-di-O-methyl, 6-O-methyl, 2,3-di-O-propyl, and 2,3-di-O-acetyl) derivatives. On methanesulfonylation and p-toluenesulfonylation, the hexakis(2,3-di-O-acetyl) derivative 16 afforded the hexakis(2,3-di-O-acetyl-6-O-methylsulfonyl 17 and 2,3-di-O-acetyl-6-O-p -tolylsulfonyl 18) derivatives, respectively. Nucleophilic displacement of 17 and 18 with iodide, bromide, chloride, and azide ions afforded the hexakis(6-deoxy-6-iodo 19, 6-bromo-6-deoxy, 6-chloro-6-deoxy, and 6-azido-6-deoxy) derivatives, respectively, of α-cyclodextrin dodeca-acetate. The hexakis (2, 3-di-O-acetyl-6-deoxy) derivative was prepared from 19. Selective glucosylation of 16 with 2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl bromide under catalysis by halide ion, followed by removal of protecting groups, furnished 6-O-α-D-glucopyranosyl-α-cyclodextrin.     

Conformational analysis of 6α- and 6β-naltrexol and derivatives and relationship to opioid receptor affinity

Naltrexol and its C? α and β desoxy, iodo, mesyl, tosyl, trifyl, dimethylcarbamyl, and diphenylcarbamyl derivatives were studied in their energy-minimized C ring chair-like and boat-like conformations using B3LYP/6-31G** and SM5.4/A to estimate aqueous solvation free energy. The results were compared to experimental opioid receptor binding affinities. The total energy difference between β conformers correlated well with MOR binding affinity, while the aqueous solvation free energy correlated well with the KOR binding affinity.     

Some Pharmaceutical Properties of a New Branched Cyclodextrin, 6-O-α-(4-O- α-D-Glucuronyl)-D-glucosylβ-cyclodextrin

Some physicochemical and biological properties of a new branched cyclodextrin, 6-O--(4-O--d-glucuronyl)-d-glucosyl--cyclodextrin GUG--CyD) were investigated. Further, theinteraction of GUG--CyD with several drugs was studied by the solubility and spectroscopic methods, and compared with those of parent -CyD and 6-O--maltosyl--CyD(₂--CyD).The hemolytic activity of GUG--CyD on rabbit erythrocytes was lower than those of -CyD and ₂--CyD. GUG--CyD and ₂--CyD showed negligible cytotoxicity on Caco-2 cells up to at least 0.1 M. The inclusion ability of GUG--CyD to neutral and acidic drugs was comparable to or slightly smaller than those of -CyD and ₂--CyD, probably because of a steric hindrance of the branched sugar. On the other hand, GUG--CyD showed greater affinity for the basic drugs, compared with -CyD and ₂--CyD, owing to the electrostatic interaction of its carboxylate anion with positive charge of basic drugs. Thus GUG--CyD may be useful as a safe solubilizing agent particularly for basic drugs.     

Diastereoselective Syntheses of (+)-α-Cyperone and Its C-10 Epimer

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1,2,4-trihydroxynaphthalene-2-O-β-D-glucopyranoside: A new powerful antioxidant and inhibitor of Aβ42 aggregation isolated from the leaves of Lawsonia inermis

Mounting evidence indicates free radicals as toxic species causing damage to human cells leading to the pathogenesis of many diseases such as neurodegenerative disease. Plant derived antioxidants are considered as promising strategy to prevent free radical toxicity. In this study, the crude extract (CE), 50%MeOH, Petroleum Ether (PE) and Ethyl acetate (EA) fractions of Lawsonia inermis leaves were investigated for their antioxidant activity and their ability to counteract amyloid-β₄₂ (Aβ₄₂) aggregation. Elution of the most bioactive fraction (EA) on silica gel column chromatography led to six sub-fractions. The most active sub-fraction (1) was further resolved on silica gel column chromatography. A new compound with powerful antioxidant and anti-Aβ₄₂ aggregation properties was purified and characterised by spectroscopic methods as 1,2,4-trihydroxynaphthalene-2-O-β-D-glucopyranoside (THNG). This finding suggests that the antioxidant and anti-Aβ₄₂ aggregation activities of L. inermis leaves are strongly correlated to this compound.     

Studies on stereocontrolled epoxidations of bis-alicyclic alcohols in steroidal skeletons: preparation of eight diastereomerically pure epoxides from cholest-4-en-3β,6β-; -3β,6α-; -3α,6β- and -3α,6α-diols

Eight diastereomerically pure epoxides have been prepared from cholest-4-en-3β,6β; -3β,6α-; -3α,6β- and -3α,6α-diols via a combination of steric, protecting group and oxidant effects on stereocontrolled epoxidations of a bis-alicyclic alcohol system within the steroidal skeleton.     

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.     

A New (–)-5′,6-dimethoxyisolariciresinol-(3″,4″-dimethoxy)-3α-O-β-D-glucopyranoside from the bark of Aglaia eximia (Meliaceae)

New (–)-5′,6-dimethoxyisolariciresinol-(3″,4″-dimethoxy)-3α-O-β-d-glucopyranoside compound was isolated from the methanol extract of the bark of Aglaia eximia (Meliaceae). The chemical structure of the new compound were elucidated on the basis of spectroscopic data including, UV, IR, HR-ESI-TOFMS, 1D-NMR, 2D-NMR and comparison with those related compounds previously reported.     

Stereoselective Syntheses of ALKYL- and ALKYL-2-THIO-α-Sialosides

ABSTRACT

Alkyl and thioalkyl α-glycosides of N-acetylneuraminic acid have been prepared in near quantitative yield and with complete stereoselectivity, under the Williamson reaction conditions using RONa or RSNa, respectively, in ROH or RSH as solvent.     

Synthesis of 6-chloronicotinates of steroidal 3β,5α,6β-triols and 3β,5-dihydroxy-6-ketones

New esters of 3β,5α,6β-trihydroxysteroids and 3β,5-dihydroxy-6-ketosteroids containing 6-chloropyridine groups characteristic of the alkaloid epibatidine were synthesized by acylation with 6-chloronicotinoylchloride. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 175-179, March-April, 2009.     

单2-O-和单6-O-(2-羟丙基)-β-环糊精结构表征

以β-环糊精和环氧丙烷为原料,分别在1.5%、30%(m/m)NaOH水溶液和β-环糊精与环氧丙烷的摩尔比为1∶7的条件下合成了2-O-(2-羟丙基)-β-环糊精和6-O-(2-羟丙基)-β-环糊精,以异丙醇-水-氨水(6∶3∶1,V/V)为洗脱液,分别经柱色谱分离得到单2-O-(2-羟丙基)-β-环糊精和单6-O-(2-羟丙基)-β-环糊精,并利用DSC,ESI-MS,1HNMR,13C NMR对单2-O-(2-羟丙基)-β-环糊精、单6-O-(2-羟丙基)-β-环糊精的结构进行了系统研究。结果发现,2-O-(2-羟丙基)-β-环糊精的热稳定性要高于6-O-(2-羟丙基)-β-环糊精。13C NMR结果表明,当β-环糊精2-位上引入取代基后,会影响2-位、1-位、3-位碳化学位移的变化,当β-环糊精6-位上引入取代基后,会影响6-位、5-位碳化学位移的变化,因此,可以用13C NMR方法有效地识别2-HP-β-CD取代基的位置。     

Syntheses of Benzoxepinoquinolinone and Benzothiepinoquinolinone

l-Benzoxepino(3, 4-b)quinolin-l3(6H)-one and its halogen,alkyl, alkoxy derivatives Va'-d' and 1-benzothiepino(3,4-b}-quinolin- 13 ( 6H)-one Vf, and its alkyl derivatives Vg, weresynthesized through cyclization of 2-(substituted phenoxymethyl)-3-quinolinecarboxylic acids Va-d and 2-[ (un)substituted phen-ylthiomethyll-3-quinolinecarboxylic acids IVf-g in the presence ofpolyphosphoric acid.The acids IV were obtained from the corresponding ethyl-esters @ whcih were prepared through refluxing ethyl 2-bromo-methyl-3-quinolinecarboxylate(1) with substituted phenol or (un)substituted thiophenol in the presence of NaOEt.The compound Vg, was allowed to react with NBS, KaBH4, NH2OH-HCl to give compounds VII , VIII, and IX, respectively.The structures of 24 new compounds have been confirmed by elemental analysis, IR and 1H NMR.     

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.