Preparation of Some Benzyl D-Glucuronatesfrom 4-Methoxybenzylidene Derivatives of D-Glucuronic Acid

Summary.  Because of the low stability of the benzyl ester linkage in benzyl 1,2:3,5-di-O-benzylidene-α-D-glucofuranuronate during the removal of the benzylidene groups by acid hydrolysis and/or hydrogenolysis, 4-methoxybenzylidene groups were used to block the free hydroxyl groups of D-glucuronic acid. Several benzyl esters of D-glucuronic acid were prepared, and their relative rates of acid catalyzed hydrolysis were determined by liquid-chromatographic separation of the reaction mixture and subsequent diode array detection. Received May 22, 2000. Accepted (revised) July 17, 2000     

Synthesis of Urine Drug Metabolites: Glucuronosyl Esters of Carboxymefloquine,Indoprofen, (S)‐Naproxen,and Desmethyl (S)‐Naproxen

Abstract

A general procedure for the synthesis of 1‐O‐acyl‐β‐D‐glucuronic acids using the benzyl 1-O-trichloroacetimidoyl-2,3,4-tri-O-benzyl-D-glucopyranuronate 6 as donor is exemplified by the synthesis of the urine metabolites of (S)‐naproxen, desmethyl (S)‐naproxen, indoprofen, and carboxymefloquine. The key intermediate benzyl 2,3,4‐tri‐O‐benzyl‐D‐glucopyranuronate 5 is easily accessible in four steps (29%) from the peracetylated β-D-glucuronic acid 1.     

Synthesis of Cryptococcus neoformans Capsular Polysaccharide Structures. Part V: Construction of Glucuronic Acid‐Containing Thioglycoside Donor Blocks

Abstract

Glucuronic acid‐containing di‐ and trisaccharide thioglycoside building blocks, ethyl (benzyl 2,3,4‐tri‐O‐benzyl‐β‐D‐glucopyranosyluronate)‐(1 → 2)‐3‐O‐allyl‐4,6‐di‐O‐benzyl‐1‐thio‐α‐D‐mannopyranoside, ethyl (benzyl 2,3,4‐tri‐O‐benzyl‐β‐D‐glucopyranosyluronate)‐(1 → 2)‐6‐O‐acetyl‐3‐O‐allyl‐4‐O‐benzyl‐1‐thio‐α‐D‐mannopyranoside and ethyl (2,3,4‐tri‐O‐benzyl‐β‐D‐xylopyranosyl)‐(1 → 4)‐[(benzyl 2,3,4‐tri‐O‐benzyl‐β‐D‐glucopyranosyluronate)‐(1 → 2)]‐3‐O‐allyl‐6‐O‐benzyl‐1‐thio‐α‐D‐mannopyranoside, corresponding to repetitive structures in the capsular polysaccharide (CPS) of Cryptococcus neoformans, have been synthesized. The blocks contain an orthogonal allyl group in the 3‐position of the mannose residue to allow formation of the (1 → 3)‐linked mannan backbone of the CPS and benzyl ethers as persistent protecting groups to facilitate access to acetylated target structures. The glucuronic acid moiety was introduced using an acetylated trichloroacetimidate donor and the xylose residue employing the benzoylated bromo sugar to ensure β‐selectivity in the couplings. Exchange to benzyl protecting groups was then performed at the di‐ or trisaccharide level. Assembly of suitable blocks employing DMTST as promoter in diethyl ether then afforded, in high yield and with stereoselectivity, a protected pentasaccharide corresponding to a C. neoformans serotype D CPS structure.     

Chloroglycidate Synthesis of a Precursor of Natural 3-Deoxy-D-manno-octulosonic Acid with Combined Protective Groups

A new oxo form of D-mannose with cyclohexylidene and benzyl protective groups is synthesized with the aim of adapting the chloroglycidate synthesis for natural 3-deoxy-D-manno-octulosonic acid. The sites of fixation of the protective groups were established by converting a model compound, 4-O-acetyl-2,3: 5,6-di-O-cyclohexylidene-aldehydo-D-mannose, into a known dicyclohexylidene-D-manno-furanose. The oxo form was reacted with methyl dichloroacetate to obtain a stereoisomeric mixture of chloroglycidates which were transformed into the corresponding pyruvate. The ketone and enol forms of the latter compound were isolated and separately characterized.     

Stereospecific Synthesis of D -Glycero- D -ido-oct-2-ulose

 D-Glycero-D-gulo-heptose reacted with 2,2-dimethoxypropane to give its 2,3:6,7-di-O-isopropylidene derivative. Its base-catalyzed addition to formaldehyde resulted in the formation of 2,3:6,7-di-O-isopropylidene-2-C-(hydroxymethyl)-D-glycero-D-gulo-heptofuranose. After acid hydrolysis of this aldolization product, a new branched-chain aldose, 2-C-(hydroxymethyl)-D-glycero-D-gulo-heptose, was obtained, which was stereospecifically rearranged under the catalytic action of molybdic acid to D-glycero-D-ido-oct-2-ulose.     

Synthesis of the Polymer of 1 {3-O[(R)-1 (L-Alanyl-D-Isoglutamyl Carbonyl) Ethyl]-α-D-Glucopyranos-6-O-Carbonycarbonyl}Ethylene

Abstract

The polymer of 1- 3-O [(R)1-(L-alanyl-D-isoglutamyl carbonyl)ethyl] α-D-glucopyranos-6-O-carbonyl ethylene was synthesized as a acryloyl type polymer by fixing the D-glucose analog (GADP) of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), which is the minimum required structure responsible for the immunoadjuvant activity of bacterial cell-wall peptidoglycan. N- [2-(1,2-O-Isopropylidene-6-O-acryloyl-α-D-glucofuranos-3-Oyl)-(R)-propionyl] -L-alanyl-D-isoglutamine benzyl ester (6) was prepared as a key monomer in the synthesis. The homopolymerization of 6 and the copolymerization of 6 with hydrophobic acryloyl monomers were carried out in benzene at 60°C by using 2,2′-azobisisobutyronitrile as a radical initiator to give homopolymer 7 and copolymer 10, respectively. Removal of isopropylidene and benzyl protecting groups from 7, 10 and 8, 11 was carried out by acid treatment with trifluoroacetic acid/water (6:1 v/v) and by catalytic hydrogenolysis with palladium carbon, respectively, to afford the homopolymer 9 and the copolymer 12.     

Stereospecific Synthesis of D-Glycero-D-ido-oct-2-ulose

Summary.  D-Glycero-D-gulo-heptose reacted with 2,2-dimethoxypropane to give its 2,3:6,7-di-O-isopropylidene derivative. Its base-catalyzed addition to formaldehyde resulted in the formation of 2,3:6,7-di-O-isopropylidene-2-C-(hydroxymethyl)-D-glycero-D-gulo-heptofuranose. After acid hydrolysis of this aldolization product, a new branched-chain aldose, 2-C-(hydroxymethyl)-D-glycero-D-gulo-heptose, was obtained, which was stereospecifically rearranged under the catalytic action of molybdic acid to D-glycero-D-ido-oct-2-ulose. Received October 17, 2000. Accepted December 4, 2000     

Synthesis of saccharide precursors for preparation of potential inhibitors of glycosyltranferases

Ethyl 6-O-tert-butyldimethylsilyl-3,4-di-O-acetyl-2-thio-α-D-fructofuranoside (Va), its β-analog (Vb); as well as benzyl 6-O-tert-butyldimethylsilyl-3,4-di-O-acetyl-2-thio-α-D-fructofuranoside (Xa) and its β-analog (Xb), having an unprotected OH group at C-1, were prepared by sequential synthesis starting from commercially available D-fructose. These compounds represent suitable nucleophiles for the preparation of model carbohydrate mimetics of a glycosyltransferase inhibitor type in transition state. The structures of all compounds were confirmed by NMR spectral data and elemental analyses.     

Synthesis of Optically Active,Ring-Substituted N-Benzyloxycarbonylphenylalanines via 2-Benzyloxycarbonylamino-2-arylalkylmalonates

Diethyl or dimethyl benzyloxycarbonylaminomalonate was reacted with ring substituted benzyl halides and the resulting arylalkyl derivatives ( 3 to 6 ) half-saponified to the DL -monoacid-monoesters ( 7 to 10 ). Decarboxylation by refluxing in dioxane afforded the N-benzyl oxycarbonyl-DL -amino acid esters ( 11 to 14 ), which were resolved into their optical antipodes by enzymic hydrolysis of the ester group with Subtilisin, type Carlsberg. Enzymic hydrolysis led to the N-benzyloxycarbonyl-L -amino acids ( 15 to 18 ) and to the corresponding D -amino acid esters. The latter were converted to the N-benzyloxycarbonyl-D -amino acids ( 19 and 20 ) by alkaline hydrolysis of the ester groups. These derivatives could be used directly for further peptide synthesis. The following compounds were prepared: N-benzyloxycarbonyl derivatives of p-methyl-L -phenylalanine ( 15 ), p-methyl-D -phenylalanine ( 19 ), p-fluoro-L -phenylalanine ( 16 ), m-fluoro-L -phenylalanine ( 17 ), m-fluoro-D -phenylalanine ( 20 ) and penta-fluoro-L -phenylalanine ( 18 ). The free amino acids were obtained by removal of the benzyloxycarbonyl group with HBr in acetic acid.     

Microbial and Enzymatic Synthesis of Optically Pure D- and L-3-Trimethylsilyl-alanine by Deracemization of D,L-5-Trimethylsilyl-methyl-hydantion

 The sterospecificities of hydantoinases and N-carbamoyl amino acid amidohydrolases (N-carbamoylases) from different microbial sources were investigated for the stereoselective syntheses of the unnatural silicon-containing amino acids D- and L-3-trimethylsilyl-alanine (3) from the respective racemic hydantoin D,L-1. In a preparative biotransformation, whole resting cells of Agrobacterium sp. IP I 671, immobilized in a Ca-alginate matrix, were used for the synthesis of amino acid D-3 in 88% yield and 95% enantiomeric excess. Since the purified D-N-carbamoylase from Agrobacterium sp. IP I 671 was shown to be 100%D-selective, the enantiomeric purity of 95% of D-3 arising from the transformation with the immobilized cells must be explained by the participation of a further, L-selective N-carbamoylase or, which is more likely, by racemization of the final hydrolysis product by the action of an amino acid racemase. Isolated hydantoinases from Bacillus thermoglucosidasius, Thermus sp., Arthrobacter aurescens DSM 3745, and Arthrobacter crystallopoietes DSM 20117 turned out to be stereospecific for the conversion of the D-form of hydantoin D,L-1. The enantiomerically pure L-form of 3 was also prepared. It was synthesized from racemic N-carbamoyl amino acid D,L-2 by enantiomer-specific hydrolysis of the L-form in presence of L-N-carbamoylase from Arthrobacter aurescens DSM 3747.     

Microbial and Enzymatic Synthesis of Optically Pure D- and L-3-Trimethylsilyl-alanine by Deracemization of D,L-5-Trimethylsilyl-methyl-hydantion

Summary.  The sterospecificities of hydantoinases and N-carbamoyl amino acid amidohydrolases (N-carbamoylases) from different microbial sources were investigated for the stereoselective syntheses of the unnatural silicon-containing amino acids D- and L-3-trimethylsilyl-alanine (3) from the respective racemic hydantoin D,L-1. In a preparative biotransformation, whole resting cells of Agrobacterium sp. IP I 671, immobilized in a Ca-alginate matrix, were used for the synthesis of amino acid D-3 in 88% yield and 95% enantiomeric excess. Since the purified D-N-carbamoylase from Agrobacterium sp. IP I 671 was shown to be 100%D-selective, the enantiomeric purity of 95% of D-3 arising from the transformation with the immobilized cells must be explained by the participation of a further, L-selective N-carbamoylase or, which is more likely, by racemization of the final hydrolysis product by the action of an amino acid racemase. Isolated hydantoinases from Bacillus thermoglucosidasius, Thermus sp., Arthrobacter aurescens DSM 3745, and Arthrobacter crystallopoietes DSM 20117 turned out to be stereospecific for the conversion of the D-form of hydantoin D,L-1. The enantiomerically pure L-form of 3 was also prepared. It was synthesized from racemic N-carbamoyl amino acid D,L-2 by enantiomer-specific hydrolysis of the L-form in presence of L-N-carbamoylase from Arthrobacter aurescens DSM 3747. Received December 20, 1999. Accepted January 7, 2000     

Synthesis of Water-Soluble “Molecular Tweezers” on the Basis of 4,4'-Diaminodiphenyl Sulfone and Monosaccharides

Novel water-soluble acyclic host molecules with a molecular tweezer topology were synthesized on the basis of 4,4'-diaminodiphenyl sulfone by the Schiff reaction with monosaccharides: D-()glucose, D-glucuronic acid -lactone, and D-gluconic acid -lactone. Optimal conditions for preparing each type of the receptor molecules were chosen.     

Nonsteroidal Constituents from Solanum Incanum L.

Sixteen compounds were isolated from the aerial parts of Solanum incanum L. These compounds included ten flavonoids ( 1‐10 ), chlorogenic acid ( 11 ), adenosine ( 12 ), benzyl‐O‐β‐D‐xylopyranosyl(1→2)‐β‐D‐glucopyranoside ( 13 ), and three phenylalkanoic acids ( 14‐16 ). The structures were determined from their physical and spectral data. Among these compounds, kaempferol 3‐O‐(6″′‐O‐2,5‐dihydroxycinnamoyl)‐β‐D‐glucopyranosyl (1→2) β‐D‐glucopyranoside ( 10 ) was identified as a new compound.     

Alkalische Hydrolyse einiger methylierter Kohlehydrate

Zusammenfassung Es wird der zeitliche Verlauf der Methanolabspaltung durch alkalische Hydrolyse bei allen Monomethyl-d-glucosen und bei 4-Methyl-d-glucuronsäure untersucht.

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Rate and time dependence of cleavage of the methoxyl group by alcaline hydrolysis of all monomethyl-d-glucoses and of 4-methyl-d-glucuronic acid is investigated.

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Mit 1 Abbildung

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Frau Prof. Dr.Erika Cremer zum Geburtstag gewidmet.     

Structure of galactomannan from seeds ofGleditsia macracantha

The structure of galactomannan from seeds ofGleditsia macracantha is studied by methylation, periodate oxidation, and partial acid hydrolysis. The principal polyglycoside chain consists of β-1→4-bonded mannopyranose units, where the mannose is substituted in the 6-position by single α-D-galactopyranose units. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 573–576, September–October, 1999.     

Synthesis of New Ureido Sugars,Derivatives of 2-Amino-2-deoxy-D-glucose and Amino Acids

Abstract

Amino acid methyl, ethyl or benzyl esters have been used as amination agents in reaction with methyl 3,4,6-tri-O-acetyl-2-deoxy-2-(4-nitrophenoxycarbonylamino)-β-D-glucopyranoside (1). Fourteen new ureido sugars, derivatives of 2-amino-2-deoxy-D-glucopyranoside and glycine, L-alanine, L-valine, L-leucine, L-phenylalanine, L-pro-line, L-aspartic acid and L-glutamic acid were obtained.     

Linear polyurethanes made from naturally occurring tartaric acid

Naturally occurring tartaric acid was used as raw material for the synthesis of novel linear polyurethanes (PURs) bearing two carboxylate side‐groups in the repeating unit. Aliphatic and aromatic PURs were obtained by reaction in solution of alkyl and benzyl tartrates with hexamethylene diisocyanate and 4,4′‐methylene‐bis(phenyl isocyanate), respectively. All the novel PURs were thermally stable and optically active. The aliphatic carboxylate‐containing PURs had M_w in the 40–70 kDa range, with PD between 2.1 and 2.5; all were semicrystalline polymers with melting temperatures between 100 and 150 °C and T_g in the 50–80 °C range. The aromatic PURs were amorphous materials with molecular weights between 18 kDa and 25 kDa and T_g above 130 °C. Hydrogenolysis of the PUR made from hexamethylene diisocyanate and benzyl tartrate yielded PURs containing up to 40% of free carboxylic side‐groups. The tartrate‐derived PURs displayed enhanced sensitivity to hydrolysis compared with their unsubstituted 2,6‐PUR homologs. The PURs bearing free carboxylic groups were unique in being degraded by water upon incubation under physiological conditions. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2391–2407, 2009     

Triterpene glycosides ofTragacantha and their genins. Cyclostipulosides A and B fromTragacantha stipulosa

Two new triterpene glycosides of the cycloartane series, which have been called cyclostipulosides A and B, have been isolated in the individual form from the roots ofTragacantha stipulosa Boviss. Their structures have been established by physicochemical methods. Cyclostipuloside A is 24R-cycloartane-3β,6α,16β,24,25-pentaol 16-O-β-D-glucopyranoside 3-O-β-D-xylopyranoside, and cyclostipuloside B is 24R-cycloartane-3β,6α,16β,24,25-pentaol 6-O-α-L-arabinopyranoside 16-O-β-D-glucopyranoside 3-O-β-D-xylopyranoside. By the acid hydrolysis of cyclostipulosides A and B we have obtained the new glycoside 24R-cycloartane-3β,6α,16β,24,25-pentaol 16-O-β-D-glucopyranoside. Institute of the Chemistry of Plant Substances, Academy of Sciences of the Republic of Uzbekistan, Tashkent, fax (371) 120 64 75. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 670–674, September–October, 1998.     

Thermochemical investigation of acid-base interactions in peptide solutions

Heat effects of interaction of D,L-α-alanyl-D,L-α-alanine, glycil-γ-aminobutyric acid, glycil-L-asparagine and D,L-α-alanyl-D,L-asparagine with KOH, LiOH and HNO₃ solutions were measured by the direct calorimetry method at 288.15, 298.15, 308.15, 318.15 K and at several values of the ionic strength created by adding KNO₃ and LiNO₃. The standard dissociation enthalpies of the investigated ligands were obtained by the extrapolation to zero ionic strength. The standard thermodynamic characteristics (ΔG ⁰ , ΔH ⁰ , ΔS ⁰ , ΔC _p ⁰) of the processes of acid-base interaction in dipeptide solutions were calculated. Several peculiarities of acid-base interaction reactions in the solutions of biologically important ligands were found. The correlations between the thermodynamic characteristics of the protolytic equilibria in the dipeptide and aminoacids solutions and the structure of these compounds were determined.     

槲树叶中的5种酚性成分

从槲树叶Quercus dentata Thunb中分离纯化得到五种酚性成分. 通过理化性质分析和光谱解析等手段确定其化学结构分别为: 2-新橙皮糖基-2,6-二羟基苯甲酸苯甲酯(1), 龙胆酸5-O-(6-O-没食子酰基)--D-吡喃葡萄糖苷(2), 3,5,7-三羟基色原酮-3-O--D-吡喃葡萄糖苷(3), 没食子酸(4), 儿茶素(5), 其中化合物1和3为新化合物.