Silylation of Cellulose and Starch – Selectivity, Structure Analysis, and Subsequent Reactions

The silylation of cellulose and starch under different starting conditions is reviewed. The control of the degree of substitution (DS) and regioselectivity in dependence of the reaction pathway are discussed in detail. The synthesis of trimethylsilyl cellulose (TMSC) in the system hexamethyldisilazane (HMDS)/ammonia leads to partially and completely silylated products controlled by the amount of the components. Hydrolytic desilylation of TMSC in tetrahydrofuran (THF)/ammonia gives the partially desilylated products. The desilylation proceeds statistically along the polymer chains. The reaction of cellulose dissolved in N,N-dimethylacetamide (DMA)/LiCl with bulky thexyldimethylchlorosilane (TDSCl) in the presence of imidazole leads to 2,6-di-O-TDS cellulose. The silylation of starch dissolved in dimethylsulfoxide (DMSO) with TDSCl/pyridine results in the formation of regioselectively 2-O and 6-O functionalized silyl ethers with DS values up to 1.8. 6-O Silyl ethers of cellulose and starch were synthesized with TDSCl highly activated in the reaction system N-methylpyrrolidone (NMP)/ammonia. Two- dimensional NMR techniques after subsequent modifications of the remaining OH groups have been established as important methods for the characterization of the substitution pattern of the described silyl ethers. In the case of starch, the distribution of the substituents could be detected not only in the anhydroglucose units (AGU) but also in the non-reducing end groups (NEG).     

Regioselective Silylations of C-2 Hydroxyl Groups of Cyclodextrins Dependent on Reaction Temperature

Silylations of the C-2 hydroxyl group of cyclodextrins were carried out using t-butyldimethylsilyl imidazole in the presence of 4A molecular sieves in N,N-dimethylformamide. A unique aspect of this silylation method is the temperature dependence of the regioselectivity; silylation at 0 °C regioselectively favored the C-6 position to afford mono-6-O-t-butyldimehylsilyl-cyclodextrins, whereas silylation at 140 °C exhibited high regioselectivity on the C-2 hydroxyl group.     

Hydrogen bonds in regioselectively substituted cellulose derivatives

Formation of hydrogen bonds in various cellulose derivatives, 2,3-di-O- and 6-O-substituted cellulose ethers, were characterized by FTIR and solid-state CP/MAS¹³C-NMR. The polymers were synthesized by regioselective substitution of hydroxyl groups and had a uniform structure. Since their three hydroxyl groups (OH) are selectively blocked, the cellulose derivatives appeared to form specific inter- and intramolecular hydrogen bonds. The characteristic OH stretching frequencies in IR spectra and the C-1 chemical shift in CP/MAS spectra of 6-O-substituted cellulose derivatives indicated existence of two equivalent intramolecular hydrogen bonds between ether oxygen and OH groups at 3-OH-O5′ and O6-HO-2′ [Figure 3(C)]. Influence of the substituents at the C-6 position on the formation was not significant except trityl group. Behavior of the hydrogen bonds in 6-O-tritylcellulose were also discussed. © 1994 John Wiley & Sons, Inc.     

Synthesis of carboxyl cellulose sulfates with regioselective sulfation and regiospecific oxidation using cellulose trifluoroacetate as intermediates

Synthesis of cellulose sulfates (CSs) and carboxyl cellulose sulfates (COCSs) with regioselectively or regiospecifically distributed functional groups within anhydroglucose units was reported. CS with regioselectively distributed sulfate groups at 2,3-O- or 2,6-O-position were homogeneously synthesized and cellulose trifluoroacetate (CTFA) was used as intermediates. The trifluoroacetyl groups were detected primarily at 6-O-position and their distributions could be altered by changing the amount of trifluoroacetyl anhydride (TFAA). Various sulfating agents were used for further homogeneous sulfation of CTFA. The total degree of sulfation (DS_S) and the distribution of sulfate groups within the repeating units were affected by the amount of TFAA, the type and amount of sulfating agents. Subsequent homogenous 4-acetamide-TEMPO or TEMPO-mediated oxidation of CS led to COCS with carboxyl groups regiospecifically distributed at C6 position, which may be interesting structural mimics for natural occurring heparin.     

Water solubility of regioselectively 2,3-O-substituted carboxymethylcellulose

A series of 2,3-O-carboxymethylcelluloses (CMC's), which are regioselectively substituted at the C-2 and C-3 position, were prepared and their water solubility was examined. It was found that the lower limit for the degree of substitution (DS) value of water-soluble 2,3-O-CMC is about 0.3. This value was almost the same as that of CMC prepared in a slurry of isopropyl alcohol/water with isopropyl chloroacetate and sodium hydroxide, showing that the uniform alkylation is rather important to convert cellulose into water-soluble derivatives.     

Convenient synthesis and NMR spectral studies of variously substituted <Emphasis Type="Italic">N</Emphasis>-methylpiperidin-4-one-<Emphasis Type="Italic">O</Emphasis>-benzyloximes

Abstract  A series of variously substituted N-methylpiperidin-4-one-O-benzyloximes were synthesized by three different methods. Among them, the direct conversion of 2,6-diarylpiperidin-4-ones into the corresponding oxime ethers (method A) was proved to be better than the other two methods in the sense of good yield, convenience, easy work-up and quick reaction time. All the synthesized compounds are characterized by IR, Mass and NMR (¹H NMR, ¹³C NMR, ¹H-¹H COSY, ¹H-¹³C COSY and HMBC) spectral studies. The conformational preference of the synthesized oxime ethers with/without alkyl and aryl substituents at C-3/C-5 and C-2/C-6 is discussed using the spectral data. The observed chemical shifts and coupling constants suggest that the synthesized oxime ethers adopt chair conformation with equatorial orientation of all the substituents, whereas 1-methyl-3-isopropyl-2,6-diphenylpiperidin-4-one-O-benzyloxime also exists in boat conformation. Based on the NMR data, the effects of oximination on ring carbons and their associated protons and alkyl substituents are discussed. In addition, the effect of NMe group on the 2,6-diarylpiperidin-4-one-O-benzyloximes was also studied. Graphical abstract        

Binding cellulose and chitosan via click chemistry: Synthesis,characterization, and formation of some hollow tubes

A novel cellulose‐click‐chitosan polymer was prepared successfully in three steps: (1) propargyl cellulose with degrees of substitution (DS) from 0.25 to 1.24 was synthesized by etherification of bamboo Phyllostachys bambusoide cellulose with propargyl chloride in DMA/LiCl in the presence of NaH. The regioselectivity of propargylation on anhydrous glucose unit determined by GC‐MS was in the order of 2 >> 6 > 3; (2) the functional azide groups were introduced onto the chitosan chains by reacting chitosan with 4‐azidobenzoic acid in [Amim]Cl/DMF and the DS ranged from 0.02 to 0.46; (3) thus, the cellulose‐click‐chitosan polymer was obtained via click reaction, that is, the Cu(I)‐catalyzed Huisgen 1,3‐dipolar cycloaddition reaction, between the terminal alkyne groups of cellulose and the azide groups on the chitosan backbone at room temperature. The successful binding of cellulose and chitosan was confirmed and characterized by FTIR and CP/MAS ¹³C NMR spectroscopy. TGA analyses indicated that the cellulose‐click‐chitosan polymer had a higher thermal stability than that of cellulose and chitosan as well as cellulose–chitosan complex. More interestingly, some hollow tubes with near millimeter length were also observed by SEM. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

PREPARATION AND STRUCTURE OFFIVE DERIVATIVES OFβ-(1→3)-D-GLUCAN ISOLATED FROM PORIA COCOS SCLEROTIUM*

A new solvent of cellulose (1.5 mol/L NaOH/0.5 mol/L urea aqueous solution) was used as one of the homogeneous reaction media of polysaccharides for methylation, hydroxyethylation and hydroxypropylation. A water insoluble β-(1→3)-D-glucan, sample PCS3-Ⅱ, isolated from fresh sclerotium of Poria cocos was sulfated in dimethyl sulfoxide (Me2SO), carboxymethylated in NaOH, isopropanol solution, as well as methylated, hydroxyethylated and hydroxypropylated in the new solvent system, respectively, to obtain five water-soluble derivatives coded as S-PCS3-Ⅱ, C-PCS3-Ⅱ, M-PCS3-Ⅱ, HE-PCS3-Ⅱand HP-PCS3-Ⅱ. Their chemical structure and distribution of substitution were characterized by infrared spectroscopy (IR), elementary analysis (EA), ^1H-NMR, ^13C-NMR, 2D-COSY, 2D-TOCSY and 2D-^1H-detected ^1H ^13C HMQC spectra. The results reveal that the relative reactivity of hydroxyl groups of the β(1→3)-D-glucan is in the order C-6 ＞ C-4 ＞ C-2 on the whole. The substitution of the samples S-PCS3-Ⅱ, C-PCS3-Ⅱ and M-PCS3-Ⅱ occurred mainly at C-6 position and secondly at C-4 and C-2 positions, and that of HE-PCS3-Ⅱ occurred at C-6 and C-4 positions and of HP-PCS3-Ⅱ almost completely occurred at C-6 position. The degrees of substitution (DS) obtained from ^13C-NMR range from 0.23 to 1.27. The water solubility of the derivatives is in the order S-PCS3-Ⅱ ＞ C-PCS3-Ⅱ ＞ M-PCS3-Ⅱ ＞ HE-PCS3-Ⅱ ＞ HP-PCS3-Ⅱ. This work provides a novel and nonpolluting process for the methylation, hydroxyethylation and hydroxypropylation of β-(1→3)-D-glucan.     

Syntheses of 2,6-O-alkyl celluloses: influence of methyl and ethyl groups regioselectively introduced at O-2 and O-6 positions on their solubility

2,6-Di-O-ethyl (2E6E) (1), 2-O-ethyl-6-O-methyl (2E6M) (2), and 6-O-ethyl-2-O-methyl (6E2M) (3) celluloses were synthesized via ring-opening polymerization of glucose orthopivalate derivatives. 2,6-Di-O-methyl cellulose (2M6M) was insoluble in any common solvents, though it was not expected. On the other hand, cellulose derivative 1 (2E6E) was soluble in chloroform. Introduced positions of alkyl groups on cellulose affected solubilities of cellulose derivatives. Their solubility in chloroform decreased in the order: polymer 1 (2E6E) > polymer 2 (2E6M) > polymer 3 (6E2M) ≫ 2M6M.     

Interaction of cellulose with amine oxide solvents

Cellulose I, mainly as ramie or as Avicel microcrystalline cellulose, has been monitored by optical microscopy and by ¹³C CPMAS NMR, over the course of its dissolution in hot N-methylmorpholine N-oxide solvent. Its interaction with the near-solvent N-ethylmorpholine N-oxide and related non-solvents has also been investigated. NMR shows that N-methylmorpholine N-oxide partly converts crystalline cellulose I into amorphous solid cellulose. The changes in chemical shift imply increased flexibility at the glycosidic bonds. In contrast, N-ethylmorpholine N-oxide converts cellulose I to cellulose III_I, without dissolution. Microscopy shows that the ramie fibres swell laterally, and at least some also shorten longitudinally, during dissolution. Model studies using methyl--d-glucopyranose show no evidence from ¹³C chemical shifts for different modes of binding with different solvents. However, N-methylmorpholine N-oxide binds more strongly to methyl--d-glucopyranose in DMSO than does N-ethylmorpholine N-oxide, whereas N-ethylmorpholine N-oxide binds better to H₂O. Also, ¹³C T ₁ values for aqueous cellobioside show increasing rotational freedom of the –CH₂OH sidechains as N-methylmorpholine N-oxide is added. Together, these observations imply the initial penetration of solvents and near-solvents between the molecular cellulose sheets. Subsequently, N-methylmorpholine N-oxide breaks H-bonds, particularly to O-6, just sufficiently to loosen individual chains and then dissolve the sheets.     

Synthesis of diblock copolymers with cellulose derivatives. 3. Cellulose derivatives carrying a single pyrene group at the reducing-end and fluorescent studies of their self-assembly systems in aqueous NaOH solutions

Novel cellobiose and cellulose (DP _n =ca. 30) derivatives, N-(1-pyrenebutyloyl)-4-O-(β-d-glucopyranosyl)-β-d-glucopyranosylamine (6), N-(15-(1-pyrenebutyloylamino)-pentadecanoyl)-4-O-(β-d-glucopyranosyl)-β-d-glucopyranosylamine (7), N-(1-pyrenebutyloyl)-β-cellulosylamine (13), N-(15-(1-pyrenebutyloylamino)-pentadecanoyl)-β-cellulosylamine (14) carrying a pyrene group as a single fluorescent probe at the reducing end, were prepared in order to investigate their self-assembly systems in solutions. The relative intensity of the excimer emission at ca. 480 nm due to dimerized pyrenes (intensity I _E) to the monomer emission at ca. 380 nm due to isolated pyrene (intensity I _M), i.e., I _E/I _M, was monitored in various solutions. In water/dimethyl sulfoxide (DMSO) mixed solvent (0–98%, v/v), the ratio I _E/I _M remained low (0.04) for compound 6 over the range of water concentrations, indicating that pyrenes at C-1 position of compound 6 were diffused. On the other hand, the ratio I _E/I _M increased (0.04–4.96) for compound 7 with the increase in water concentration, indicating that pyrenes at C-1 position were associated. In aqueous NaOH solutions (4.4–17.5%, w/w), compound 14 showed a large increase in the ratio I _E/I _M (0.84–8.14) with the increase in NaOH concentration, compared to compound 13 (0.06–0.41). It was found that the association of hydrophobic groups at the reducing-end of cellulose could be controlled by the hydrophilic–hydrophobic balance of compounds and the solvent polarity.     

Preparation and Characterization of 6-<Emphasis Type="Italic">O</Emphasis>-(4-stearyloxytrityl)Cellulose acetate Langmuir–Blodgett Films

Multilayer films of 2,3-di-O-acetyl-6-O-(4-stearyloxytrityl)cellulose (ASTC) were prepared and investigated. The fairly high surface pressure (π)–area (A) isotherms (36– 47 mN/m) suggest that the balky and hydrophobic trityl group contribute to form a condensed monolayer. The cellulose derivative formed a homogeneous monolayer at 10 mN/m. The monolayer on the water surface was transferred successfully at 10 mN/m onto various substrates by modifying the preparation methods, to form Z-type multilayer films. The ultraviolet–visible (UV–Vis) absorbance was independent of the number of layers, indicating that each layer is made of definite number of anhydroglucose unit (AGU). The monolayer thickness determined from atomic force microscope (AFM) and ellipsometry was calculated to be about 1.9 nm, suggesting that the long alkyl chain in the film has a so-called hairy-rod type structure. This is the first paper about the Z-type LB film prepared from cellulose derivatives having long mono-alkyl chain only at 6-O-position.     

Synthesis and antibacterial activity of methylated N-(4-N,N-dimethylaminocinnamyl) chitosan chloride

The methylated chitosan containing different aromatic moieties were synthesized by two steps, the reductive amination and the methylation. The chemical structures of all methylated derivatives, methylated N-(4-N,N-dimethylaminocinnamyl) chitosan chloride (MDMCMCh), methylated N-(4-pyridylmethyl) chitosan chloride (MPyMeCh), and N,N,N-trimethyl chitosan chloride (TMChC) were characterized by ATR-FTIR and ¹H NMR spectroscopy. The molecular weights of the methylated chitosan derivatives were determined by gel permeation chromatography. The results revealed that the molecular weights of chitosan and N-aryl chitosan derivatives could be reduced by the methylation process. The degree of N-substitution (DS) and the degree of quaternization (DQ) were calculated by ¹H NMR ranged from 50% to 76%, and 28% to 82%, respectively. The water solubility of the methylated chitosan derivatives decreased with increasing concentration and pH. The antibacterial studies of these methylated chitosan derivatives were carried out by using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) methods against Escherichia coli ATCC 25922 (Gram-negative) and Staphylococcus aureus ATCC 6538 (Gram-positive) bacteria. It was found that the MDMCMCh showed higher antibacterial activity than TMChC while MPyMeCh exhibited reduced antibacterial activity against both bacteria at the same DQ level. In comparison to each of the chemical structure, it was found that the antibacterial activity was not only dependent on the DQ but it was also dependent on the positively charged location and the molecular weight.     

Availability and state of order of hydroxyl groups on the surfaces of microstructural units of crystalline cotton cellulose

The relative accessibilities of the hydroxyl groups of the D-glucopyranosyl units of hydrocellulose have been studied by means of the reaction of N,N-diethylaziridinium chloride, which produces 2-(diethylamino)ethyl cellulose. The deviation in the distribution of substituents among the 2-O-, 3-O-, and 6-O-positions of the D-glucopyranosyl residues in a hydrocellulose from that in a disordered cellulose in which the three types of hydroxyl groups are equally accessible is the basis for estimating the selective accessibilities of the hydroxyl groups in the crystalline cellulose. A particular hydrocellulose, lying within the range of leveling-off degree of polymerization, was studied in detail; this hydrocellulose, designated EHC (“Exemplar Hydrocellulose”), was formed from fibrous cotton by hydrolysis for 0.67 hr in 2.5N hydrochloric acid at reflux. EHC exhibited higher selective accessibility (larger deviation from equal accessibility) of the hydroxyl groups at C-2, C-3, and C-6, than samples of hydrocellulose formed in shorter or longer periods of hydrolysis. This selective accessibility is discussed in terms of intra- and intermolecular hydrogen bonding on the surfaces of crystalline microstructural units in EHC.     

Cellulosic polyelectrolytes: synthetic pathways to regioselectively substituted ammonium and phosphonium derivatives

Cationic polysaccharide polyelectrolytes are important synthetic targets for drug and gene delivery, especially by encapsulation of nucleic acids and proteins through electrostatic interactions. They also have potential as paracellular permeability enhancers that may increase transport across the gastrointestinal (GI) epithelium, especially for therapeutic hydrophilic macromolecules. Semisynthetic chitosan has been more heavily investigated as a cationic polysaccharide polyelectrolyte. This study explores the synthetic conditions needed to produce ammonio and phosphonio cellulose derivatives regioselectively by halogen displacement at C-6 while maximizing the degree of substitution (DS) of cationic substituent. Regioselective substitution was successful, however there were found to be some limitations to the DS and solubility of ammonium derivatives prepared in this way (highest DS 0.43); conversely, water-soluble 6-phosphonio-6-deoxycellulose derivatives were produced with DS > 0.5, with highest DS of 0.73. The repulsion between accumulating positive charges was confirmed as a likely source of DS limitation since high DS (0.9) of 6-triethylamino cellulose was synthesized under comparable conditions. Further reaction of 6-ammonio-co-6-bromo derivatives with a thiol produced 6-ammonio-co-6-thiolated products with improved aqueous solubility. The thiol DS of 0.68 determined by elemental analysis confirmed substitution of residual bromide from low DS (0.30) ammonium products to give essentially complete substitution at C-6.     

Synthesis of regioselectively brominated cellulose esters and 6-cyano-6-deoxycellulose esters

The control of regiochemistry in the synthesis of polysaccharide derivatives is one of the most significant scientific challenges in the field. Its importance is only further highlighted by the individual successes in synthesis of regioselectively substituted derivatives, in particular cellulose esters and ethers, over the last 20 years. The availability of these samples and studies of their properties versus randomly substituted analogs has shown clearly that properties like solubility, aggregation phenomena, and optical properties depend heavily on the regiochemistry of substitution. We report here on the one-pot synthesis of novel 6-bromo-6-deoxy-2,3-O-acylcellulose derivatives, which as more organic soluble derivatives of 6-bromo-6-deoxycellulose should allow broader exploitation of the highly regioselective cellulose 6-bromination chemistry. We illustrate the potential of these new derivatives by conversion to 6-cyano-6-deoxycellulose esters.     

Modifications at the 6-O-position of 1-deoxynojirimycin: facile and efficient synthesis of 6-O-alkylated-N-octyl-1-deoxynojirimycin derivatives

A straightforward synthesis of N-alkylated 1-deoxynojirimycin derivatives modified at the 6-O-position has been described. The key intermediate in the synthesis of target compounds was 2,3,4-tri-O-benzyl-1,5-dideoxy-1,5-imino-D-glucitol, which was prepared from 2,3,4,6-tetra-O-benzyl-1,5-dideoxy-1,5-imino-D-glucitol. Optimal conditions have been established for the synthesis of the key intermediate by varying reaction parameters. Reductive amination and subsequent alkylation of the 6-O-position followed by hydrogenolysis were the main reaction steps, which gave target compounds 6-O-ethyl-N-octyl-1,5-dideoxy-1,5-imino-D-glucitol and 6-O-butyl-N-octyl-1,5-dideoxy-1,5-imino-D-glucitol. This synthetic route is flexible and can be useful for the synthesis of other lipophilic iminosugar derivatives.     

The synthesis ofN-acetyl-β-l-fucosamine-1-phosphate and uridine 5′-diphospho-N-acetyl-β-l-fucosamine

Uridine 5′-(2-acetamido-2,6-dideoxy-β-l-galactopyranosyl) diphosphate (uridine 5′-diphospho-N-acetyl-β-l-fucosamine) was synthesized. The key intermediate, 3,4-di-O-acetyl-2-azido-2,6-dideoxy-β-l-galactopyranosyl dibenzyl phosphate, was prepared by a previously unknown reaction of cesium dibenzyl phosphate with the corresponding α-glycosyl nitrate and was then converted into theN-acetylated glycosyl phosphate and nucleoside diphosphate sugarsvia 3,4-di-O-acetyl-2-amino-2,6-dideoxy-β-l-galactopyranosyl phosphate using mildN-acetylation andO-deacetylation as the last synthetic steps. Published inIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 11, pp. 1919–1923, November, 2000.     

Regioselective synthesis of 4-aryl-3,4-dihydro-1,3,5-triazino[2,1-<Emphasis Type="Italic">a</Emphasis>]isoindol-2-ones

The condensation of binucleophilic 3-amino-1-arylimino-1H-isoindoles with bifunctional 1-chloro-benzylisocyanates occurs regioselectively resulting in 3,4-dihydro-1,3,5-triazino[2,1-a]isoindol-2-one derivatives. The structures of the synthesized compounds were unambiguously established by NOE experiments. Correspondence: Olha V. Hordiyenko, Chemistry Department, Kyiv National Taras Shevchenko University, 01033 Kyiv, Ukraine.     

Synthesis of lipooligosaccharides related to nodulation factors ofRhizobium sp. NGR234

Trisaccharide analogs of natural nodulation factors fromRhizobium sp. NGR234, namely, 2-acetamido-2-deoxy-4-O-(2-deoxy-2-hexadecanamido-β-d-glucopyranosyl)-6-O-(2-O-methyl-α-l-fucopyranosyl)-d-glucopyranose and its derivatives containing a 4-O-acetyl or a 3-O-sulfo group at thel-fucose residue, were synthesized. The oligosaccharides synthesized were shown to posses biological activity. Laboratoire de Biologie Moléculaire des Plantes Supérieures (LBMPS), Université de Genève, 1 ch. de l'Impératrice, 1292 Chambesy-Genève, Suisse. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya No. 3, pp. 513–518, March, 1998.