TBAF-catalyzed deacylation of cellulose esters: Reaction scope and influence of reaction parameters

In order to expand its utility and understand how to carry it out most efficiently, the scope of the highly regioselective, tetrabutylammonium fluoride (TBAF) catalyzed deacylation of cellulose acetates has been investigated, including the influence of key process parameters: solvent, temperature, and water content. Reactions in DMSO, THF, MEK and acetone afforded similar extents of deacylation and regioselectivity. Reaction with TBAF in DMSO at 50 °C for 18 h was the most efficient process providing regioselective deacylation at O-2/3. All results were consistent with our previous mechanistic proposals. Furthermore, we demonstrate that TBAF-catalyzed deacylation is also effective and regioselective with cellulose acetate, butyrate, and hexanoate triesters, and even with a cellulose ester devoid of alpha protons, cellulose tribenzoate. These reactions displayed regioselectivity for deacylation at O-2/3 similar to that observed earlier with cellulose acetate (DS 2.4).     

Mode of action on deacetylation of acetylated methyl glycoside by cellulose acetate esterase from Neisseria sicca SB

The regioselective deacetylation of purified cellulose acetate esterase from Neisseria sicca SB was investigated on methyl 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranoside and 2,3,4,6-tetra-O-acetyl-beta-D-galactopyranoside. The substrates were used as model compounds of cellulose acetate in order to estimate the mechanism for deacetylation of cellulose acetate by the enzyme. The enzyme rapidly deacetylated at position C-3 of methyl 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranoside to accumulate 2,4,6-triacetate as the main initial reaction product in about 70% yield. Deacetylation was followed at position C-2, and generated 4,6-diacetate in 50% yield. The enzyme deacetylated the product at positions C-4 and C-6 at slower rates, and generated 4- and 6-monoacetates at a later reaction stage. Finally, it gave a completely deacetylated product. For 2,3,4,6-tetra-O-acetyl-beta-D-galactopyranoside, CA esterase deacetylated at positions C-3 and C-6 to give 2,4,6- and 2,3,4-triacetate. Deacetylation proceeded sequentially at positions C-3 and C-6 to accumulate 2,4-diacetate in 55% yield. The enzyme exhibited regioselectivity for the deacetylation of the acetylglycoside.     

Synthesis of D-allose fatty acid esters via lipase-catalyzed regioselective transesterification

The acylation of the rare sugar, D-allose (the C-3 epimer of D-glucose), with fatty acid vinyl esters was successfully carried out using Candida antarctica lipase in acetonitrile at 45 degrees C to give D-allose 6-alkanoates with high regioselectivity in good yields.     

New 6-butylamino-6-deoxycellulose and 6-deoxy-6-pyridiniumcellulose derivatives with highest regioselectivity and completeness of reaction

This paper investigates the nucleophilic substitution (S(N)) reactions of tosylcellulose with butylamine and pyridine, respectively. The S(N) reactions of tosylcellulose 1 (DS(Total) 2.02; DS(C-6) 1.0) with butylamine carried out at 25, 50, 75 and 100 degrees C in both dimethyl sulfoxide (DMSO) and pure butylamine showed that the regioselectivity of substitution at C-6 of cellulose is temperature dependent: the highest regioselectivity at C-6 can be reached at 25 and 50 degrees C; substitution at C-2 also occurred at 75 and 100 degrees C. The substitution speed in pure butylamine is greater than that in the presence of DMSO. A complete and regioselective substitution at C-6 with a DS of 1.0 was obtained under the conditions of 50 degrees C, 40 h in butylamine. The substitution reactions of 1 with pyridine carried out at 25, 50, 75 and 100 degrees C for 24h in DMSO did not occur. In contrast to this the S(N) reactions done in pure pyridine showed that a temperature- and steric-dependent, regioselective substitution took place at C-6 at temperatures from 25 to 145 degrees C. The highest regioselectivity and completeness at C-6 can be obtained at 100 degrees C for 90 h, whereas at 145 degrees C substitution also occurs at C-2. The results were proved by 1H NMR and 13C NMR spectroscopy.     

Chiral discrimination with regioselectively substituted cellulose esters as chiral stationary phases

Four kinds of cellulose derivatives, including two regioselectively substituted cellulose esters (6-O-acetyl-2,3-di-O-benzoyl cellulose and 2,3-di-O-acetyl-6-O-benzoyl cellulose), were synthesized so that the effects of their functional group distribution on their chiral discrimination ability could be examined. The degree of substitution by functional groups appeared to have a critical effect on the separation in most cases, but the type of the functional group at the C-6 position also significantly influenced chiral discrimination when a series of neutral arylalcohol derivatives were used as racemates. Copyright 2000 Wiley-Liss, Inc.     

Regioselective synthesis of cellulose ester homopolymers

Regioselective synthesis of cellulose esters is extremely difficult due to the small reactivity differences between cellulose hydroxyl groups, small differences in steric demand between acyl moieties of interest, and the difficulty of attaching and detaching many protecting groups in the presence of cellulose ester moieties without removing the ester groups. Yet the synthesis of homopolymers of particular regioselectively substituted anhydroglucose esters is of critical importance to allow us to determine the analytical characteristics of such homopolymers, their structure-property relationships, and to obtain guidance that may ultimately enable identification and synthesis of cellulose derivatives with superior properties for various applications. We report here a new, general synthesis of both cellulose-2,6-O-diesters and cellulose-2,6-A-O-3-B-O-triesters with a high degree of regioselectivity, employing 3-O-allylcellulose as a key protected precursor. 3-O-Allylcellulose was identified as a protected intermediate with high potential for the synthesis of these derivatives with the aid of molecular modeling of corresponding glucose analogs. We report also the first analytical and structure property studies of these regioselectively substituted cellulose esters.     

Modification of cellulose fiber surfaces by use of a lipase and a xyloglucan endotransglycosylase

A strategy for the modification of cellulose fiber surfaces was developed that used the ability of Candida antarctica lipase B (CALB) to acylate carbohydrates with high regioselectivity, combined with the transglycosylating activity of the Populus tremula x P. tremuloides xyloglucan endotransglycosylase 16A (PttXET16A). Xyloglucan oligosaccharides (XGOs) prepared from tamarind xyloglucan were acylated with CALB as a catalyst and vinyl stearate or gamma-thiobutyrolactone as acyl donors to produce carbohydrate molecules with hydrophobic alkyl chains or reactive sulfhydryl groups, respectively. The modified XGOs were shown to act as glycosyl acceptors in the transglycosylation reaction catalyzed by PttXET16A and could therefore be incorporated into high M(r) xyloglucan chains. The resulting xyloglucan molecules exhibited a high affinity for cellulose surfaces, which enabled the essentially irreversible introduction of fatty acid esters or thiol groups to cellulose fibers.     

Tailored cellulose esters: synthesis and structure determination

A broad variety of cellulose esters with complex and sensitive (against hydrolysis and light) structures was synthesized homogeneously in N,N-dimethylacetamide (DMAc)/LiCl and in the new solvent dimethyl sulfoxide (DMSO)/tetrabutylammonium fluoride (TBAF) via in situ activation of the carboxylic acids with N,N'-carbonyldiimidazole (CDI). New esters of chiral (-)-menthyloxyacetic acid, of unsaturated 3-(2-furyl)-acrylcarboxylic- and furane-2-carboxylic acid, acids with crownether moieties (4'-carboxybenzo-18-crown-6), and with carboxymethyl-beta-cyclodextrin were accessible in a one-pot reaction. Because of the mild conditions and the efficiency of the reaction via imidazolides, very pure and highly functionalized cellulose derivatives were obtained up to a degree of substitution of 2.5 possessing a degree of polymerization in the range of the starting cellulose. Structure determination was carried out by different one- and two-dimensional NMR techniques confirming the high purity of the esters and a pronounced regioselectivity for the primary OH function. The structural features, the purity, the solubility, and the film forming properties, make these materials desired products for the preparation of membranes with tailored separation characteristics.     

Exclusive and complete introduction of amino groups and their N-sulfo and N-carboxymethyl groups into the 6-position of cellulose without the use of protecting groups

A new regioselective synthesis of 6-amino-6-deoxycellulose with a DS 1.0 (degree of substitution) at C-6, and its 6-N-sulfonated and its 6-N-carboxymethylated derivatives, without using protecting groups is described in this paper. The reaction conditions were optimized for preparing cellulose tosylate with full tosylation at C-6 and partial tosylation at C-2 and C-3. The nucleophilic substitution (S(N)) reaction of the tosyl group by NaN(3) at low temperature of 50 degrees C in Me(2)SO was achieved completely at C-6, whereas the tosyl groups at C-2 and C-3 were not displaced. In contrast to this, at 100 degrees C the tosyl groups at C-6, and also those at C-2 and C-3, were replaced by azido groups. This regioselective reaction that depends on temperature makes it possible to reach a selective and quantitative S(N) reaction at C-6 at low temperatures. In the subsequent reduction step with LiAlH(4), the azido group at C-6 was reduced to the amino group, and the tosyl groups at C-2 and C-3 were simultaneously completely removed. Also reported is a temperature-dependent, regioselective and complete iodination by nucleophilic substitution of the tosyl group at C-6 at 60 degrees C. At higher temperatures from 75 to 130 degrees C, substitution is also observed to occur at C-2. The selective iodination at 60 degrees C was employed to confirm the complete tosylation at C-6 of cellulose. The reaction products were identified by four different independent quantitative methods, namely 13C NMR, elemental analysis, ESCA, and fluorescence spectroscopy. 6-N-Sulfonated and 6-N-carboxymethylated cellulose derivatives were also synthesized. The new derivatives are potent candidates for structure-function studies, e.g., studies in relation to regioselectively 2-N-sulfonated and 2-N-carboxymethylated chitosan derivatives.     

Regioselective monoacylation of cyclomaltoheptaose at the C-2 secondary hydroxyl groups by the alkaline protease from Bacillus subtilis in nonaqueous media

Transesterification of cyclomaltoheptaose (beta-CD) with divinyl butanedioate, divinyl hexanedioate, and divinyl decanedioate, catalyzed by the alkaline protease from Bacillus subtilis in anhydrous DMF for 5 days, furnished the corresponding vinyl-beta-CD derivatives. The products were characterized by ESI-MS, (1)H NMR, (13)C NMR, IR, and DSC. The results indicated the products to be monosubstituted esters, with monoacylation occurring at the C-2 secondary hydroxyl groups of beta-CD. The regioselectivity of the monoacylation as catalyzed by alkaline protease was not affected by the chain length of the acyl donor.     

Novel and Highly Efficient Regioselective Route to Helicid Esters by Lipozyme TLL

Highly regioselective acylation of helicid with fatty acid vinyl esters catalyzed by the lipase from Thermomyces lanuginosus has been successfully performed for the first time. For the enzymatic caproylation of helicid, under the optimal conditions, initial reaction rate was 33.2 mM/h, and substrate conversion and regioselectivity were greater than 99%. In addition, the acyl recognition of the enzyme in the regioselective acylation of helicid was investigated. The results showed that although 6’-O-acyl derivatives of helicid were exclusively obtained with all the tested acyl donors, the enzymatic reaction rate varied widely with different acyl donors, presumably owing to their different interactions with the active site of the lipase. It is also interesting that the different configuration of only one hydroxyl group at C-3 in helicid couldn’t affect the lipase-catalyzed esterification and helicid has the same regioselectivity as that of D-glucose and arbutin.     

Facile synthesis of arabinomannose penta- and decasaccharide fragments of the lipoarabinomannan of the equine pathogen, Rhodococcus equi

Pentasaccharide repeating unit 20 of the lipoarabinomannan from the equine pathogen, Rhodococcus equi, and its dimer 31, were synthesized. The pentasaccharide was obtained by assembling a benzoylated 2,6-branched mannosyl trisaccharide acceptor 13 with a free hydroxyl group at C-2' of the mannose residue attached to the core mannose residue by (1 --> 6)-linkage, followed by coupling with 2,3,5-tri-O-benzoyl-alpha-D-arabinofuranosyl-(1 --> 2)-3,4,6-tri-O-benzoyl-alpha-D-mannopyranosyl trichloroacetimidate (18), and by deacylation. Meanwhile, the decamer 31 was obtained by firstly preparing a benzoylated mannose (1 --> 6)-linked tetrasaccharide backbone 26 with 2-, 2"-O-ClAc, and 2'-, 2'-O-Ac groups, respectively, then by dechloroacetylation and subsequent condensation with perbenzoylated trichloroacetimidate, and then by deacetylation and subsequent coupling with 18, and finally, by deacylation.     

2-O-Methyl- and 3,6-Di-O-methyl-cellulose from Natural Cellulose: Synthesis and Structure Characterization

For the first time, 2-O-methyl- (2MC) and 3,6-di-O-methyl-cellulose (36MC) were synthesized via 3-O-allyl- and 3-O-methyl-cellulose, respectively. Position 6 of 3-O-allyl- and 3-O-methyl-cellulose was protected with the 4-methoxytrityl groups. The reaction time and temperature were optimized to achieve a high regioselectivity at C-6 and to prevent the introduction of the 4-methoxytrityl group at C-2 of the polymer. It was found that the substituent at C-3 of 3-O-functionalized celluloses influenced the reactivity of the hydroxyl group at C-6. The structure was characterized by means of (1)H and (13)C NMR spectroscopy of the acetates of 2MC and 36MC. 2MC and 36MC were soluble in water and did not show thermoreversible gelation.     

On the mechanism of lithiation of uridine derivatives with lithium dialkylamides

Efficiency and regioselectivity (C-6 or C-5) in the lithiation of uridine derivatives were examined by using LDA (lithium diisopropylamide) and LTMP (lithium 2,2,6,6-tetramethylpiperidide). It revealed that rotation of the C-2' substituent caused steric hindrance on approaching the lithiating agent to the C-6 position, providing evidence that the lithiation takes place through their syn-conformers.     

A facile one-step synthesis of delta 1,4-3-keto bile acid esters by iodoxybenzene and benzeneselenic anhydride

A facile one-step conversion of stereoisomeric methyl 3-hydroxycholanoates to 1,4-dien-3-one, by treatment in boiling toluene with iodoxybenzene catalyzed by benzeneselenic anhydride, is described. The direct oxidation-dehydrogenation at C-3 is applicable to other cholanoates (hyodeoxycholic, chenodeoxycholic, ursodeoxycholic, deoxycholic, and cholic) when the hydroxyl groups at C-6, C-7, or C-12 are protected. Without protection at C-6 and C-7, the products from hyodeoxycholic, chenodeoxycholic, ursodeoxycholic, and cholic esters are complex mixtures, whereas, methyl deoxycholate yields the 1,4-dien-3,12-dione cleanly.     

Biosynthèse de cellulose bactérienne à pertir de glycérol sélectivement deutérié en position 1, 2, ou 3: Etude par résonance magnétique nucléaire

Glycerol specifically deuterated at C-1, C-2, or C-3 was prepared and used for the biosynthesis of bacterial cellulose with Acetobacter xylinum.The material obtained were converted into glucitol hexaacetate and analyzed by 250-MHz nuclear magnetic resonance and mass spectrometry. The spectra indicated that the protons of the C-3 position of the starting glycerol were incorporated as substituents of the C-6 and C-1 positions of the cellulose. Similarly, protons of the C-2 and C-5 positions of the cellulose came essentially from water and the protons bonded at the C-3 and C-4 positions of the cellulose from protons bonded to C-1 of the starting glycerol.     

The Use of Enzymes to Regioselectively Deacylate Sucrose Esters

The deacylation activity of a range of hydrolytic enzymes on octa-O-acetyl sucrose has been investigated. From a total of 96 enzymes tested, 55 were active; 16 produced only heptaacetates, 12 produced hexaacetates and 27 could deacylate at 3 or more positions. Hydrolysis could only be achieved at 5 positions; the 3 primary positions plus the 4 and 4' positions. The remaining 3 positions (2, 3 and 3') were not hydrolysed. Only one enzyme tested was sufficiently active at all 5 positions to yield 2,3,3'-tri-O-acetyl sucrose. Acyl migration occurred on the glucose ring of partially deacylated products, but this could be minimised by conducting reactions between pH 4 and 5. A range of specifically protected sucrose esters was obtained by using a combination of enzymes in sequence. No activity towards pentanoyl and butyryl esters of sucrose was detected. This finding was exploited by using butyryl groups as protecting groups in the enzymic deacylation of sucrose acetyl esters. These strategies can be used to synthesise specifically substituted sugars.     

Preparation of 6-deoxy-6-fluorocellulose

6-Deoxy-6-fluorocellulose was prepared from cellulose 2,3-diacetate (1) or cellulose 2,3-dibenzoate (2) in various solvents, and was characterized by ¹⁹F and ¹³C NMR measurements. The best product, having ds of 0.95 at C-6 and 0.04 at C-3, was prepared from cellulose 2,3-dibenzoate in nitrobenzene. Other combinations of starting material and solvent gave a lower (≈ 0.8) ds of fluorine at C-6 and higher (≈ 0.12) at C-2 or C-3. Substitution at C-2 was observed when the combination of 1 and 1,4-dioxane, or 2 and chloroform was used. The products substituted at C-2 by fluorine were relatively resistant to acid hydrolysis.     

Catalytic action of comicelles containing imidazolyl and hydroxyl groups in the hydrolysis of enantiomeric esters

The rate constants for hydrolysis of the enantiomers of amino acid p-nitrophenyl esters catalyzed by bifunctional comicellar catalysts containing the imidazolyl and hydroxyl groups have been determined at pH 7.30, 0.02 m phosphate buffer, and 25°C. The kinetic analysis suggests a reaction scheme which involves acylation followed by deacylation at the imidazolyl group. Although no appreciable cooperative catalytic efficiencies are observed between the bifunctional groups in the acylation step, it is found that the deacylation rates are thus accelerated by surfactant hydroxyl groups, and some of the stereoselective acyl transfer reaction occurs from the imidazolyl to the hydroxyl group in optically active comicellar systems.     

Hydrogen bond formation in regioselectively functionalized 3-mono-O-methyl cellulose

The hydrogen bond systems of cellulose and its derivatives are one of the most important factors regarding their physical- and chemical properties such as solubility, crystallinity, gel formation, and resistance to enzymatic degradation. In this paper, it was attempted to clarify the intra- and intermolecular hydrogen bond formation in regioselectively functionalized 3-mono-O-methyl cellulose (3MC). First, the 3MC was synthesized and the cast film thereof was characterized in comparison to 2,3-di-O-methyl cellulose, 6-mono-O-methyl cellulose, and 2,3,6-tri-O-methyl cellulose by means of wide angle X-ray diffraction (WAXD) and (13)C cross polarization/magic angle spinning NMR spectroscopy. Second, the hydrogen bonds in the 3MC film were analyzed by means of FTIR spectroscopy in combination with a curve fitting method. After deconvolution, the resulting two main bands (Fig. 3) indicated that instead of intramolecular hydrogen bonds between position OH-3 and O-5 another intramolecular hydrogen bond between OH-2 and OH-6 may exist. The large deconvoluted band at 3340cm(-1) referred to strong interchain hydrogen bonds involving the hydroxyl groups at C-6. The crystallinity of 54% calculated from the WAXD supports also the dependency of the usually observed crystallization in cellulose of the hydroxyl groups at C-6 to engage in interchain hydrogen bonding.