SYNTHESIS OF METHYL 𝛼-D-ALTROPYRANOSIDE

Methyl 2,3-anhydro-4,6-O-benzyIidene-𝛼-D-aIIopyranoside

• In a two-necked, 250-ml round-bottomed flask fitted with a mechanical stirrer unit and a pressure-equalising funnel protected with a calcium chloride guard-tube place a solution of 11.7g (0.0195 mol) of methyl 4,6-O-benzylidene-2,3-di-O-toluene-p-sulphonyl-𝛼-D-glucopyranoside in 150ml of dichloro-methane. 

• Cool the solution to 0°C by means of an ice-salt bath and add a solution of sodium methoxide in methanol [prepared from 2.3 g (0.1 mol) of sodium and 40 ml of methanol] dropwise with stirring. 

• When the addition is complete remove the stirrer and funnel, stopper the flask and leave it in a refrigerator for 48 hours and then at room temperature for a further 24 hours. 

• Extract the dichloromethane solution with water until the aqueous washings are neutral, dry over magnesium sulphate and remove the solvent from dichloromethane to give the pure product, m.p. 195-199 °C, [𝛼]ᴅ²º + 140° (c2 in CHC1₃). The yield is 4.2 g (82%).

Methyl 4,6-O-benzyIidene-𝛼-D-aItropyranoside

• Triturate 4.0 g (0.015 mol) of the foregoing anhydro derivative in a mortar with a solution of 5g 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-𝛼-D-altropyranoside, m.p. 174 °C, [𝛼]ᴅ²º+115° (c2 in CHCI₃).

Methyl 𝛼-D-altropyranoside

• Hydrolyse the benzylidene protecting group by heating, at 60 °C for 1 hour, 3.5 g (0.025 mol) of the foregoing compound in a mixture of 140 ml of warm water and 7 ml of 0.05 m sulphuric acid. 

• Concentrate the residual solution to 50 ml using a rotary evaporator under reduced pressure (benzaldehyde is removed during the process) and make just alkaline (phenolphthalein) with 0.1m barium hydroxide solution (prepared by diluting a cold saturated solution with an equal volume of water). 

• Remove the barium sulphate by filtration (Whatman No. 42 paper), wash the residue with water and concentrate the filtrate and washings to a syrup (rotary evaporator). 

• Dissolve the residue in a little methanol, add ether until a slight turbidity is observed and set the solution on one side to crystallise. 

• The resulting methyl 𝛼-D-altroside may be recrystallised from methanol/ether and has m.p. 107-108 °C, [𝛼]ᴅ²º+ 126° (c3 in H₂O); the yield is 2.1 g (88%).