(2S,4S)-2,4,5-Trihydroxypentanoic acid 4,5-acetonide could be produced through the following synthetic routes.

A. Tri-O-acetyl-D-xylono-1,4-lactone 2. a) oxidation. A 250-mL, three-necked, round-bottomed reaction flask equipped with a magnetic stirrer, thermometer, and an addition funnel is charged with 30.0 g (0.20 mol) of D-xylose and 80 mL of water. After the clear aqueous solution is cooled with an ice-water bath, 34.0 g (0.23 mol) of potassium carbonate is added in portions, keeping the temperature below 20°C. After the mixture is cooled to below 5°C, 12 mL (0.22 mol) of bromine is added dropwise over 90 min, keeping the temperature of the reaction mixture below 10°C. The orange solution is stirred at that temperature for 30 min, then at room temperature overnight. The reaction is quenched by careful addition of 88% formic acid (2.5 mL) to afford a colorless solution. The solution is concentrated at 50°C on a rotary evaporator and 20 mL of acetic acid is added. The mixture is concentrated again at 50°C to remove any residual water.

b) Acetylation. The residual white semi-solid is transferred to a 500-mL, three-necked, round-bottomed reaction flask with the aid of warm acetic acid (40 mL). The flask is equipped with a mechanical stirrer, thermometer, and an addition funnel. After the suspension is warmed to 50°C, 180 mL (1.9 mol) of acetic anhydride is added dropwise over 90 min, keeping the temperature between 50–55°C. After the mixture is stirred at that temperature overnight and then cooled to room temperature, 200 mL of water is added. The mixture is extracted with 200 mL of dichloromethane (CHA. Tri-O-acetyl-D-xylono-1,4-lactone 2. a) Bromine oxidation. A 250-mL, three-necked, round-bottomed reaction flask equipped with a magnetic stirrer, thermometer, and an addition funnel is charged with 30.0 g (0.20 mol) of D-xylose and 80 mL of water. After the clear aqueous solution is cooled with an ice-water bath, 34.0 g (0.23 mol) of potassium carbonate is added in portions, keeping the temperature below 20°C. After the mixture is cooled to below 5°C, 12 mL (0.22 mol) of bromine is added dropwise over 90 min, keeping the temperature of the reaction mixture below 10°C. The orange solution is stirred at that temperature for 30 min, then at room temperature overnight. The reaction is quenched by careful addition of 88% formic acid (2.5 mL) to afford a colorless solution. The solution is concentrated at 50°C on a rotary evaporator and 20 mL of acetic acid is added. The mixture is concentrated again at 50°C to remove any residual water.

b) Acetylation. The residual white semi-solid is transferred to a 500-mL, three-necked, round-bottomed reaction flask with the aid of warm acetic acid (40 mL). The flask is equipped with a mechanical stirrer, thermometer, and an addition funnel. After the suspension is warmed to 50°C, 180 mL (1.9 mol) of acetic anhydride is added dropwise over 90 min, keeping the temperature between 50–55°C. After the mixture is stirred at that temperature overnight and then cooled to room temperature, 200 mL of water is added. The mixture is extracted with 200 mL of dichloromethane (CH₂Cl₂). The organic layer is washed with 200 mL of water. The combined aqueous layers are back-extracted with 100 mL of CH₂Cl₂. The combined organic layers are placed in a 1-L Erlenmeyer flask. After the solution is cooled with an ice-water bath, 200 mL of 2 N sodium hydroxide is added and the mixture is stirred for 30 min. The aqueous layer is separated and back-extracted with 50 mL of CH₂Cl₂. The combined organic layers are washed with 200 mL of brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue (54 g) is suspended in 50 mL of . To the stirred suspension, 70 mL of hexane is added dropwise. After stirring at room temperature for 1 hr, the mixture is cooled with an ice-water bath for 30 min. The precipitate is filtered and washed with a cold 1:2 ethyl acetate/hexane mixture (2 × 60 mL) to yield 39.3–40.7 g (71.6–74.2%) of 2 as light beige crystals, mp 96–97°C (lit.2 mp 94–95°C).

B. Di-O-acetyl-3-deoxy-D-arabino-1,4-lactone 3. A 300-mL, bench-top, high-pressure reactor is charged with 9.83 g (35.8 mmol) of 2, 1 g of Raney nickel, and 65 mL of ethyl acetate. After 7.5 mL (73 mmol) of triethylamine is added, the pressure in the bomb is immediately raised to 1000 psi with hydrogen. After the mixture is stirred vigorously at room temperature (15°C) for 3 hr, the temperature is adjusted to 30°C, and the stirring is continued for 24 hr. The pressure is released, and the bomb is flushed with nitrogen. The catalyst is removed by filtration and washed with ethyl acetate ( CAUTION! Fire hazard!). The combined filtrate and washes are washed with 75 mL of water. The aqueous layer is back-extracted with 25 mL of ethyl acetate. The combined organic layers are then washed with 75 mL of 1 N hydrochloric acid. The aqueous layer is back-extracted again with 25 mL of ethyl acetate and this extract is combined with the original organic layer. After washing with 75-mL portions of saturated sodium bicarbonate solution, and brine, the organic layer is dried over sodium sulfate and the solvent is removed to give ca. 6.5 g of crude product. The crude product is dissolved in 7 mL of warm ethyl acetate. Cooling to room temperature with stirring results in crystallization of 3. Hexane (13 mL) is added dropwise to the slurry. After the mixture is stirred at room temperature for 1 hr, it is stored in a refrigerator overnight. The precipitate is filtered and washed with a cold 1:4 ethyl acetate/hexane mixture (6 mL) to yield 5.8 g (75%) of 3 as a white solid, mp 68–70°C (lit.2 mp 69–71°C).

C. (2S,4S)-2,4,5-Trihydroxypentanoic acid 4,5-acetonide methyl ester 4. A 100-mL, round-bottomed reaction flask equipped with a magnetic stirrer, reflux condenser, and an argon inlet tube is charged with 5.4 g (25 mmol) of the diacetate 3, 0.5 g (2.5 mmol) of p-toluenesulfonic acid monohydrate, and 5 mL of methanol. After the mixture is refluxed for 3 hr and cooled to room temperature, 18 mL (140 mmol) of 2,2-dimethoxypropane is added. After 3 hr of stirring, sodium acetate (powder, 0.41 g, 5 mmol) is added and the mixture is stirred for 20 min to quench the reaction. Ethyl acetate (50 mL) and saturated sodium bicarbonate solution (50 mL) are added to the reaction mixture. The organic layer is removed and the aqueous layer is back-extracted twice with 25-mL portions of ethyl acetate. The combined organic layers are washed with 25 mL of brine, dried over sodium sulfate, and concentrated to afford 5.5 g of a colorless oil. Distillation through a short path distillation apparatus (with no forerun) gives 4.6 g of 4 (90% yield) as a colorless oil, bp 71–78°C (0.1 mm).

GC analysis of the product on a capillary column shows the diastereomeric purity to be 98.9%. Enantiomeric integrity is confirmed after conversion to the corresponding p-phenylbenzoate by HPLC analysis on a chiral column.Cl₂). The organic layer is washed with 200 mL of water. The combined aqueous layers are back-extracted with 100 mL of CH₂Cl₂. The combined organic layers are placed in a 1-L Erlenmeyer flask. After the solution is cooled with an ice-water bath, 200 mL of 2 N sodium hydroxide is added and the mixture is stirred for 30 min. The aqueous layer is separated and back-extracted with 50 mL of CH₂Cl₂. The combined organic layers are washed with 200 mL of brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue (54 g) is suspended in 50 mL of ethyl acetate. To the stirred suspension, 70 mL of hexane is added dropwise. After stirring at room temperature for 1 hr, the mixture is cooled with an ice-water bath for 30 min. The precipitate is filtered and washed with a cold 1:2 ethyl acetate/hexane mixture (2 × 60 mL) to yield 39.3–40.7 g (71.6–74.2%) of 2 as light beige crystals, mp 96–97°C (lit.2 mp 94–95°C).

B. Di-O-acetyl-3-deoxy-D-arabino-1,4-lactone 3. A 300-mL, bench-top, high-pressure reactor is charged with 9.83 g (35.8 mmol) of 2, 1 g of Raney nickel, and 65 mL of ethyl acetate. After 7.5 mL (73 mmol) of triethylamine is added, the pressure in the bomb is immediately raised to 1000 psi with hydrogen. After the mixture is stirred vigorously at room temperature (15°C) for 3 hr, the temperature is adjusted to 30°C, and the stirring is continued for 24 hr. The pressure is released, and the bomb is flushed with nitrogen. The catalyst is removed by filtration and washed with ethyl acetate ( CAUTION! Fire hazard!). The combined filtrate and washes are washed with 75 mL of water. The aqueous layer is back-extracted with 25 mL of ethyl acetate. The combined organic layers are then washed with 75 mL of 1 N hydrochloric acid. The aqueous layer is back-extracted again with 25 mL of ethyl acetate and this extract is combined with the original organic layer. After washing with 75-mL portions of saturated sodium bicarbonate solution, and brine, the organic layer is dried over sodium sulfate and the solvent is removed to give ca. 6.5 g of crude product. The crude product is dissolved in 7 mL of warm ethyl acetate. Cooling to room temperature with stirring results in crystallization of 3. Hexane (13 mL) is added dropwise to the slurry. After the mixture is stirred at room temperature for 1 hr, it is stored in a refrigerator overnight. The precipitate is filtered and washed with a cold 1:4 ethyl acetate/hexane mixture (6 mL) to yield 5.8 g (75%) of 3 as a white solid, mp 68–70°C (lit.2 mp 69–71°C).

C. (2S,4S)-2,4,5-Trihydroxypentanoic acid 4,5-acetonide methyl ester 4. A 100-mL, round-bottomed reaction flask equipped with a magnetic stirrer, reflux condenser, and an argon inlet tube is charged with 5.4 g (25 mmol) of the diacetate 3, 0.5 g (2.5 mmol) of p-toluenesulfonic acid monohydrate, and 5 mL of methanol. After the mixture is refluxed for 3 hr and cooled to room temperature, 18 mL (140 mmol) of 2,2-dimethoxypropane is added. After 3 hr of stirring, sodium acetate (powder, 0.41 g, 5 mmol) is added and the mixture is stirred for 20 min to quench the reaction. Ethyl acetate (50 mL) and saturated sodium bicarbonate solution (50 mL) are added to the reaction mixture. The organic layer is removed and the aqueous layer is back-extracted twice with 25-mL portions of ethyl acetate. The combined organic layers are washed with 25 mL of brine, dried over sodium sulfate, and concentrated to afford 5.5 g of a colorless oil. Distillation through a short path distillation apparatus (with no forerun) gives 4.6 g of 4 (90% yield) as a colorless oil, bp 71–78°C (0.1 mm).

GC analysis of the product on a capillary column shows the diastereomeric purity to be 98.9%. Enantiomeric integrity is confirmed after conversion to the corresponding p-phenylbenzoate by HPLC analysis on a chiral column.