Other Alkyl and Aryl Ethers

The 6-, and 6,6 -trityl ethers of a- and j3-cellobiose have been produced by standard methods, and boron trifluoride etherate in methanol has been used as a detritylation procedure for primary ethers. A range of common ether, ester, and acetal groups were stable to the reagent. Removal of trityl ethers in the nucleoside series has been effected using trifluoroacetic acid, sometimes diluted with butanol.  

Several substituted benzyl ethers have been examined. As part of a study of lignin-carbohydrate bonding, vanillyl alcohol was treated with glucose in aqueous acetate buffer at 60 °C and gave 48% of an anomeric mixture of the 6-ethers (1). In work on the same theme l,2 5,6-di-0-isopropylidene-a-D- 

D-Mannitol 1,2,5,6-tetraoctadecyl ether has been made from the corresponding di-O-isopropylidene derivative by way of the 3,4-di-p-methylbenzyl ether using a phase-transfer procedure. and dodecoxymethyl derivatives of glucose were prepared directly by use of dodecoxymethyl chloride. The isomeric mono-substituted and the di- and tri-substituted products were separated.  

Methyl 4,6-0-benzylidene-a-D-glucopyranoside treated with bis(2-chloro-, 2-iodo-, or 2-tosyloxy-ethyl)ether gave the crown ethers (2) and (3) which were obtained in about 15% yield (by a phase-transfer procedure). Isomeric crown ethers are also mentioned in Chapter 23. 

Other Alkyl and Aryl Ethers.- Two references to allylatlon and benzylatlon appear in the section on methyl ethers. The intramolecular ly etherifled flavan-4-ol glucoside (1) has been Isolated 

A compilation of carbohydrate benzylatlons and other alkylations employing alkyl triflates has appeared. Application of David s procedure to the preparation and selective monoalkylation 

The compatibility of benzyl, M-methoxybenzyl, and 3,M-dlmethoxy-benzyl ether protecting groups has been demonstrated, benzyl ethers being selectively removed by hydrogenolysls with Raney nickel, but 3, -dimethoxybenzyl ethers being more readily removed by DDQ (2,3-dichloro-5 6-dicyano-l,4-benzoqulnone) oxidation. 

Further crown ethers incorporating carbohydrate diol units have 

Mixtures of mono- to tetra-O-(pentyloxymethyl) ethers of methyl 

Other Alkyl and Aryl Ethers.- Procedures for the selective removal of allyl ether in the presence of allyloxycarbonyl ester protecting groups, or vice versa, using palladium and iridium catalysts have been published in full (cf. Vol.19, p.l5). A reference to ester migration during 0 -allylatlon is covered in Chapter 7. 

Many examples of the selective deprotection of benzyl, 4-methoxy-benzyl (MPM), and 3,4-dlmethoxybenzyl (DMPM) protected hydroxy groups have been detailed. Benzyl ethers but not MPM or DMPM ethers are cleaved on hydrogenolysls (H2- Raney Ni), while DMPM 

Separable mixtures of 2 - and 3 -0 -( 4-methoxybenzyl)-nucleoside derivatives have been obtained from the stannous chloride catalyzed 

2-Pyridylmethyl, 2-quinolylmethyl, and 3-methyl-6-nltro-3H-indol-2-ylmethyl ethers have been prepared by phase-transfer catalyzed 

Crown ethers and their acyclic analogues, incorporating sugar 

Other Alkyl and Aryl Ethers.—Selective benzylation of 0-3 of methyl 4,6 O-benzylidene-a-D-mannopyranoside has been noted in the previous section, while 2,3,4,5-tetra-O-benzyl-L-arabinose diethyl dithioacetal and 2,3,4,5-tetra-O-benzyl-D-arabinose dibenzyl and ethylene dithioacetals have been prepared by benzylation of the thioacetals using benzyl chloride and potassium hydroxide. 

An improved synthesis of 2,4,6-tri-O-benzyl-D-galactopyranose has been accomplished by way of benzylation ofallyl 3-0-allyl-2,6-di-0-benzyl-a-D-galactopyrano-side, which was obtained by regiospecific allylation of the 3,4-0-dibutylstannylene derivative of allyl 2,6-di-O-benzyl-a-o-galactopyranoside (see Vol. 10, p. 122). 

Alkylation of metal chelates of sucrose with allyl halides and sodium bromo-acetate in DMSO yielded mono-O-allylated and mono-O-carboxymethylated derivatives. A new acidic monosaccharide from the O-specific lipopolysaccharide of Shigella dysenteriae type 3 has been identified as 4-0-[(/ )-l-carboxy-ethyl]-D-glucopyranose on the basis of chemical and mass-spectral evidence and by its synthesis by alkylation of methyl 2,3,6-tri-0-benzyl-a(P)-D-glucopyranoside with (5)-2-chloropropionic acid, esterification (with diazomethane), hydrogenolysis, and acid hydrolysis.  

A convenient procedure for the tritylation of secondary hydroxy-groups of sugars is based on the use of triphenylmethylium perchlorate or tetrafluoroborate in 

Fernandez-Bolanos and S. Munoz Guerra, An. Quim., 1977,73, 458 (Chem. Abs., 1977,87,152 478w). 

Other Alkyl and Aryl Ethers.- 3 -0 -Allyl ethers of methyl 3-lacto-slde and two N-acylated 2-amlno-2-deoxy-lactose B-glycosldes were obtained by reaction of the dibutylstannylene complexes of these 

The products from perbenzylation (BnBr-KOH-DMSO) of six aldoses have been determined by - C-n.m.r. spectroscopy. After chromatographic removal of dibenzyl ether, the 8-pyranoside could be Isolated in yield from D-xylose, D-glucose, and D-mannose  

D-galactose yielded an inseparable mixture of a-furanoslde and 6-pyranoside (present in 53 and 8 yields respectively), while L-arablnose and D-rlbose gave more complex anomeric and ring size isomeric mixtures. Partial benzylatlon (BnCl-LlOH) of methyl 

Pour alternative procedures for synthesizing benzyl 2-acetamido-3,6-di- -benzyl-2-deoxy-6-D-glucopyranoside, each Involving 

Muramyl dlpeptide analogues which have 2-0-(l-carboxyethyl)-sub-stituents on an amino-sugar ring are covered in Chapter 9. 

Other Alkyl and Aryl Ethers.—A temporary, non-participating 2-0-allyl group has been used in the synthesis of benzyl 6-(9-(2-0-allyl-3,4,6-tri-0-benzyl-a-D-galactopyranosyl)-2,3,4-tri-0-benzyl-a-D-galactopyranoside its removal was effected by isomerization and hydrolysis.  

The use of l-oxido-3-methyl-2-pyridyldiazomethane (45) has been recommended for the synthesis of dinucleotides the reagent reacts with ribonucleosides to give a mixture of the corresponding 2 - and 3 -ethers [e.g. (4Q] that can be 

Several 2,4-dinitrophenyl ethers of D-glucose have been prepared these ethers are stable towards acids but not towards bases, and are liable to migrate under very weakly basic conditions. The use of 2,3-diphenyl-2-cyclopropenyl ethers in the synthesis of disaccharides has been noted in Chapter 3. 

SOyl Ethers.—t-Butyldiphenylsilyl chloride reacts preferentially with the primary hydroxy-group of sugar derivatives (e.g. methyl a-D-glucopyranoside), although secondary hydroxy-groups also react if sufficient reagent is used. t-Butyl- 

Selective phase-transfer benzylatlon of methyl 4,6- -benzylidene-13 l4 

Partial benzylatlon (BnBr-NaH-DMF) of methyl a-L-fucopyranoside gave complex mixtures the 2- and 3-0-benzyl ethers ( 2 1, 5055) were obtained from monomolar benzylatlon, while the 2,4- and 2,3-dlethers ( 3 lj 50 ) were obtained from dimolar benzylatlon. 

Reductive cleavage of benzylidene acetals has been further examined. Using sodium cyanoborohydride-hydrogen chloride, 4,6-0 -benzylldene derivatives of hexopyranosides are opened selectively 

6-0 -allyl ethers, e.g. (2), in good yield. By contrast, similar 

Me a- and g-D-Glc) and other alkylating agents gave more complex 

6- -isopropylidene-L-ascorbic acid has also been investigated. The perdeuterioallyl group has been shown to be useful for simplifying n.m.r. spectra of allyl-protected carbohydrates. The synthesis of perdeuterioallyl bromide from propynoic acid and the 

A large number of a a-dideuterlobenzyl (i.e. PhCD2 ) ethers of monosaccharides have been prepared so that their n.m.r. spectra could be compared with those of normal benzyl ethers.Partial benzylation of methyl a-D-mannopyranoside yielded either the 2,3,6- 

PhCH2Cl-K0H). Several partially benzylated lactoses have been 

New methods for cleavage of benzyl ethers have been reported. Catalytic transfer hydrogenolysis using ammonium formate as donor over palladlum-on-charcoal has been found to work better than with formic acid or cyclohexene over palladium catalysts. Trityl ethers were also cleaved but not benzylldene acetals. Ozone (0 /02, 

2 Other Alkyl and Aryl Ethers - A number of 3-0-aminoalkyl-l,2-0-isopro-pylidene-a-D-gluco-or xylo-furanoses have been synthesized and evaluated for antiviral activity. Some 6-0-alkyl-a-D-glycopyranosides have been prepared by displacement of 6-0-tosylates with alkoxides, while the regioselectivity of 3- or 5-0-ether formation on l,2-0-isopropylidene-4,6-di-0-benzyl-/n o-inositol has been shown to depend on the nature of the 0-alkylating agent. A facile synthesis of methyl 2-or 3-0-allyl-5-0-benzyl-p-D-ribofuranoside has been described.  

The synthesis of peptidomimetics based on a D-glucose or D-allose scaffold featured 2,3-di-0-alkyl-6-0-aryl-4-0-carboxymethyl-pyranose compounds/ while a muramic acid analogue has been used in the solid phase synthesis of peptido-glycan monomers for the generation of a combinatorial library/ 

The synthesis of four diastereomeric lignin-carbohydrate complex model compounds 1 has been described, while an amphiphilic porphyrin substituted with both 6-0-galactopyranosyl and cholesteryloxy units has been synthesized.  

A study on the selectivity of stannylene acetal-mediated alkylation of methyl 4,6-0-benzylidene-a-D-glucopyranoside has concluded that increased bulk of the alkyl groups on tin and a non-polar or no co-solvent increase the proportion of 0-2 mono-ethers formed.The tin-mediated allylation and benzylation of 1,2-0- 

Carbohydrate Chemistry, Volume 30 The Royal Society of Chemistry, 1998 

2 Other Alkyl and Aryl Ethers. - Pilosidine 1, a fused ether-glycoside, was isolated from rhizomes of Curculigo pilosa, an African plant. The synthesis and applications of carbohydrate-derived amphiphilic perfluoroalkyl ethers have been reviewed.  

Mono-O-allyl derivatives of o-fructose have been prepared in order to test the specificity of the fructose transporter GLUT5. Tris(triphenylphosphine)ruthe-nium(II) dichloride is an excellent catalyst for the isomerization of allyl to prop-l-enyl ethers in a de-O-allylation procedure. The catalyst avoids the problem of reduction of the alkene as a side reaction. Another method uses Pd(0)-catalysed allyl transfer to p-toluenesulfinic acid for the cleavage of allyl ethers on a solid support.  

The tritylation of alcohols under neutral conditions has been achieved using p-methoxybenzyl trityl ether in the presence of DDQ. A selective cleavage of trityl ethers by CBr4-MeOH has been attributed to the formation of traces of HBr. Ceric ammonium nitrate on silica gel rapidly cleaves trityl and mono and di-methoxytrityl ethers whereas CeCb-Nal in refluxing acetonitrile effects the selective cleavage of trityl and dimethoxytrityl ethers under neutral conditions.  

2 Other Alkyl and Aryl Ethers. - Diisopropylidene derivatives of D-glucose and D-fructose have been 0-alkylated, hydrolysed and reduced affording 3-0-alkyl-D-glucitol and -D-mannitol derivatives. Methyl 3, 4 -0-isopropylidene-p-D-lactoside has been converted into methyl 3, 4 -di-0-M-hexyl- and n-octyl-P-D-lactosides and these ethers were tested for their lyotropic phase behaviour, while 6 -0-alkyl ethers of 6-O-a-D-galactopyranosyl-D-glucopyranose have been prepared and their liquid-crystal properties determined.  

Benzylation of the 5-amino-5-deoxy-pentoside 3 via its 2,3-O-dibutylstannylene derivative afforded a 1 1 mixture of the 2-0- and 3-0-benzyl ethers, whereas tritylation and silylation under the same conditions generated predominantly the 2-O-protected derivative. Similarly, benzylation of the D-erythronolactone 4 via its 0-dibutylstannylene derivative gave predominantly the 2-O-benzyl ether 5 while reductive opening (TiCU, HSiEts) of the corresponding 2,3-0-benzylidene compound afforded the 3-0-benzyl ether 6. Partial benzylation (0.9 eq NaH, DMF, BnBr) of sucrose has afforded 42% of 2-0-benzyl-sucrose, isolated as its 3,4,6,r,3, 4, 6 -heptaacetate. The molecular electrostatic potential profile of sucrose apparently predicts that the 2-OH group is the most electropositive of the eight hydroxy-groups.  

Benzyl ethers have been removed in the presence of 4-bromobenzoates without debromination using anhydrous ferric chloride in dichloromethane and TFA in dichloromethane has been used to effect removal of 0-4-methoxybenzyl protecting groups.  

The association constants between the synthetic receptor 12 and a series of p-nitrophenyl a- and P-glycosides of D-glucose, D-mannose, D-galactose, D-xylose, L-fucose and L-arabinose have been examined in order to probe carbohydrate - 

Pyridinium salts of some sugar sulfates can be desulfated and silylated under certain silylating conditions.  

Liptak, F. Pckar, J. Janossy, I. Jodal, P. Fugedi, J. Harangi, P. Nanasi, and J. Szejtli, Acta Chem. Acad. Sci. Hung., 1979, 99, 201. 

Selective benzoylation (and allylation) of methyl (and benzyl 4-O-benzyl-a-L-rhamnopyranoside (4) has been studied by phase-transfer catalysis and by activation via the tributyl stannate. The former reaction gave the 2,4-dibenzyl ether (5) in high yield, whereas the latter process gave mainly the 3,4-diether (6). An alternative means of obtaining the 2,4-diether (5) involved selective tritylation to give (7) followed by benzylation and removal of the trityl group. These dibenzyl ethers have been employed in the synthesis of the tetrasaccharide repeating unit of the immunodeterminant of Klebsiella serotype K36 polysaccharide. Similar results have been recorded for the selective benzylation of other 4,6-blocked a-mannosides. The syntheses of 3-O-benzyl-D-ribose, 2-0-benzyl-D-ribose, and l,6-anhydro-2,3,2, 4-tetra-0-benzyl-jS-lactose have been recorded. The latter was employed in the synthesis of lacto-A -tetraose.  

Selective de-O-benzylation at primary positions by acetolysis has been described, and the procedure (c/. M, M. Ponpipom, Carbohydrate Res., 1977, 59, 311) would appear to be a convenient means of obtaining benzylated carbohydrates with the primary hydroxy-groups free. Formerly, it was necessary to employ sequential tritylation, benzylation, and detritylation in order to achieve these blocked compounds. De-O-benzylation has also been described using EtSH-Bp3, under mild conditions, and although it has not yet been applied to carbohydrates, it would appear to be of potential value.  

Takamura, T. Chiba, H. Ishihara, and S. Tejima, Chem. Pharm. Bull., 1979, 27, 1497. 

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Other Alkyl and Aryl Ethers Silyl Ethers... 

Other Alkyl and Aryl Ethers. - The reagent system of allyl ethyl carbonate and a Pd(0) catalyst, applied to carbohydrate alcohols, has been utilised for making allyl ethers under neutral conditions. The synthesis of benzyl ethers from the parent alcohols under non-basic conditions has been achieved using phenyldiazomethane and HBF4. Dibutylstannylene compounds derived from benzyl -D-lactoside and its derivatives have been regioselectively benzylated. ° Similarly, 2,2 -di-0-alkyl-4,6 4 6 -di-0-benzylidene-Qt,a-trehaloses have been prepared by regioselective alkylation of a dibutylstannylene derivative. Phase transfer catalysed benzylation... 

Other Alkyl and Aryl Ethers. - The preparation of selectively 0-alkylated saccharides, including benzyl, allyl, triphenylmethyl, and arylalkyl ethers has been reviewed. Analogues of lipids A and X incorporating 3-O-alkyl (rather than acyl) linkages have been described, and some carbohydrate monoalcohol derivatives have been alkylated with haloacetic acid ester derivatives. ° 3-C -Carboxymethyl D-glucose and D-fhictose compounds have been coupled via the carboxylic acid group to L-lysine in a search for acrosin inhibitors."... 

Other Alkyl and Aryl Ethers.- The regioselective alkylation at 0-3 of methyl 2,6-dldeoxy-a- and g-L-lyxo- and g-L-arablno-hexopyran-osldes through activation as the dlbutylstannylidene acetals has been described, whereas phase transfer catalysed benzylation... 

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