A-D-Altropyranoside derivatives

H- and F N.m.r, Data for 3-Amino-2,3-dideoxy-2-fluoro-a-D-altropyranoside Derivatives (and Their N-Containing, Synthetic Precursors)... 

B. Coxon and R. C. Reynolds, Boat conformations. Synthesis, NMR spectroscopy, and molecular dynamics of methyl 4,6-0-benzylidene-3-deoxy-3-phthalimido-a-D-altropyranoside derivatives, Carbohydr. Res., 331 (2001) 461 67. 

Methyl 4,6-0-benzylidene-3-deoxy-3-phthalimido-a-D-altropyranoside derivatives 246... 

Several other methods for the introduction of halo atoms at C-6 in hexose derivatives have been known since the late 1920s. One of the earlier methods involved the reaction of methyl 2,3,4-tri-0-acetyl-6-0-trityl-a-D-glucopyranoside with phosphorus pentachloride which resulted only in an 8% overall yield of methyl 6-chloro-6-deoxy-a-D-glucoside (57). In contrast, the reaction of methyl 2,3,4-tri-0-acetyl-6-0-trityl-a-D-altropyranoside with phosphorus tribromide and bromine afforded a 73% yield of the corresponding 6-bromo-6-deoxy derivative (91). 

Methyl 4,6-O-benzylidene-a-D-altropyranoside showed little selectivity on reaction with a unimolar proportion of benzoyl chloride43 2-and 3-O-benzoyl and 2,3-di-O-benzoyl derivatives, together with starting material, were isolated in the molar ratios of 1 1.1 1.8 1. In contrast, benzoic anhydride in pyridine gave the 2-ester in 35% yield, with only a trace of the 3-benzoate. 

Many other glycosides have been subjected to selective chlorination with sulfuryl chloride. Methyl /3-L-arabinopyranoside afforded methyl 4-chloro-4-deoxy-a-D-xylopyranoside 2,3-di(chlorosulfate) in 29% yield, whereas the a-L anomer gave357 methyl 3,4-dichloro-3,4-dideoxy-/3-i)-ribopyranoside 2-(chlorosulfate) (30%). Methyl /3-d-ribopyranoside was converted into methyl 3,4-dichloro-3,4-dideoxy-a-L-arabinopyranoside through the action of pyridine hydrochloride on its 2,3,4-tri(chlorosulfate).358 Methyl a-D-lyxopyranoside gave only the 2,3,4-tri(chlorosulfate),353 as would be expected from the disposition of its hydroxyl groups, similar to that in the rhamno- and manno-pyranosides. Methyl a-D-altropyranoside was transformed into the 6-chloro-6-deoxy 2,3,4-tri(chlorosulfate) derivative in 80% yield.353... 

A novel method of opening of oxiranes involves the use of (chlo-romethylene)dimethyliminium chloride (39) [see Section II,2c p. 250], monochlorodeoxy or dichlorodideoxy derivatives are obtained, depending upon the reaction conditions employed.83 Thus, methyl 2,3-anhydro-4,6-0-benzylidene-a-D-allopyranoside (110) reacts with 39 in 1,1,2,2-tetrachloroethane at room temperature to give, upon hydrolysis of the primary adduct 111 with an aqueous solution of sodium hydrogen carbonate, methyl 4,6-0-benzylidene-2-chloro-2-deoxy-3-0-formyl-a-D-altropyranoside (112). If a solution of 39 and 110 in 1,1,2,2-tetrachloroethane is heated at reflux temperature, methyl 3,4-0-benzylidene-2,6-dichloro-2,6-dideoxy-o -D-altropyrano-side (113) is obtained in high yield the n.m.r. spectrum of 113, like that of 47 (see Section II, 2c p. 250), showed the presence of two diastereoisomers which differed in the configuration of the benzyl-idene-acetal carbon atom. 

Methyl 4,6-0-benzyIidene-a-D-aItropyranoside. Triturate 4.0 g (0.015 mol) of the foregoing anhydro derivative in a mortar with a solution of 5 g of potassium hydroxide dissolved in 140 ml of water. Transfer the suspension to a round-bottomed flask and heat the mixture under reflux until all the solid has dissolved (about 28 hours). During this period solid material tends to creep up the inside of the flask surface shake periodically to re-suspend material. Remove the trace of insoluble matter which remains and neutralise the cooled filtrate with carbon dioxide (use phenophthalein as an indicator). Extract the solution with five 25 ml portions of dichloromethane, wash the combined extracts with a little cold water, dry over anhydrous sodium sulphate and remove the solvent under reduced pressure (rotary evaporator). Crystallise the syrup by scratching a small portion on a watch glass with ether stir the bulk syrup with ether and the seed crystals. Filter off and recrystallise the product from a small quantity of methanol to obtain 3.5 g (83%) of methyl 4,6-O-benzylidene-a-D-altropyranoside, m.p. 174 °C, [oc]d°+115° (c2 in CHCI3). 

A re-investigation of the reaction (conducted with methyllithium free from halide ion) which afforded the methylated derivative (1, R = Me, R = H), indicated that it proceeded by way of methyl 4,6-0-benzylidene-2-deoxy-2-C-methyl-a-D-altropyranoside (2, R= Me, R = H), because this compound [prepared by opening the corresponding 2,3-anhydroalloside with (methylsulfinyl)methyl carbanion, to give methyl 4,6-0-benzylidene-2-deoxy-2-C-[(methylsulfinyl) methyl]-a-D-altropyranoside (2, R = MeSOCH2, R = H), followed by reduction with Raney nickel], on treatment with methyllithium, also gave the C-methyl compound (1, R = Me, R = H).5... 

Methyl 4,6-0-benzylidene-a- and jS-n-altropyranosides have been prepared from the corresponding n-glucosides, which were first converted into the 2,3-di-p-toluenesulfonates. Subsequent treatment of the p-toluenesulfonate with sodium methoxide in the cold afforded the 2,3-anhydro derivative. The latter was then converted into the n-altroside by means of boiling potassium hydroxide, Methyl 4,6-0-benzylidene-a-D-altropyranoside is very resistant to oxidation by periodate ion and does not form a cuprammonium complex — in accordance with the expected CA conformation (34). 

The direct displacement of secondary sulfonyloxy groups of sugar derivatives by sulfur nucleophiles has received Umited study. Attempted displacement of p-tolylsulfonyloxy groups in methyl 4,6-0-benzylidene-3-O-methyl-2-O-p-tolylsulfonyl-a-D-altropyranoside or 1,2 5,6-di-0-isopro-pylidene-3-O-p-tolylsulfonyl-a-D-glucofuranose, by alkanethiolate anion in an alcohol medium, removed the p-tolylsuKonyl substituent and failed to give any (identifiable) thio sugar product. However, the 2,5-di-methanesulfonate of l,4 3,6-dianhydro-D-mannitol (64) reacted with... 

N-bromosuccinimide with methyl 3,4-0-benzylidene-2,6-dichloro-2,6-dideoxy-a-D-altropyranoside and with methyl 2-azido-3,4-0-ben-zylidene-6-chloro-2,6-dideoxy-a-D-altropyranoside gives preponderantly a 4-0-benzoyl-3-bromo derivative. ... 

For instance, methyl 4,6-(9-benzylidene-3-deoxy-2-D-methanesulfonyl-3-thioureido-a-D-altropyranoside (97) gave epimine 98 on treatment with sodium methoxide, but thiazoline derivative 99 was formed upon heating in pyridine. The corresponding derivative without the 4,6-(9-benzylidene group also afforded an epimine on treatment with methoxide. ... 

Carbohydrate derivs. A soln. containing methyl 4,6-0-benzylidene-3-0-mesyl-2-S-phenyl-2-thio-a-D-altropyranoside and l,5-diazabicyclo[5.4.0]undecene in dry dimethyl sulfoxide heated 2.5 hrs. at 80° under Ng methyl 4,6-0-benzylidene-3-deoxy-2-S-phenyl-2-thio-ct-D-e/7r/iro-hex-2-enopyranoside. Y 86%. F. e. and reagents s. S. Hanessian and A. P. A. Staub, Carbohyd. Res. 16, 419 (1971). 

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