D-Arabinonicacid,2-C-methyl-4,5-O-(1-methylethylidene)-,ethylester

To a 1000-mL three-necked flask was charged 1t (54.0 g, 0.25 mol) and acetone (500 mL); QAS-2 (11.4 g, 25.0 mmol) was added. The mixture was cooled to 0–5 °C. Solid KMnO4 (47.5 g, 0.3 mol) was added in 10 portions within 10 min. The mixture was stirred at the same temperature for 2 h, and TLC indicated complete consumption of 1t. A solution of NaHSO3 (25.0 g) in water (50 mL) was added in one portion to quench the reaction. The mixture was stirred for 15 min and then filtered on Celite, which was washed thoroughly with acetone (3 × 100 mL). The combined filtrates were concentrated to remove acetone under reduced pressure and the residue was extracted with EtOAc (3 × 150 mL). The combined organic phases were washed with sat. brine (3 × 50 mL), dried (Na2SO4), filtered, and evaporated to dryness to afford a colorless oil (57.5 g, 93 percent), which was recrystallized(petroleum ether, 200 mL) to afford the product as a white solid; yield: 51.3 g (83 percent); mp 75–76 °C. 1H NMR (400 MHz, CDCl3): δ = 4.20–4.31 (m, 3 H), 4.09 (m, 2 H), 3.93 (d, J = 8.0 Hz, 1 H), 2.52 (br, 2 H), 1.31–1.49 (m, 12 H).To a stirred solution of 271-2 (100 g, 0.47 mol) in acetone (2.0 L) was added KMnO4 (90 g, 0.57 mol) in portions at 0-5° C. The mixture was stirred at 0-5° C. for 2 h. The reaction was quenched using sat. sodium sulfite solution (600 mE). Afier 2 h, a colorless suspension was formed. The solid was removed by filtration. The filter cake was washed with EA (300 mE). The filtrate was extracted with EA (3x300 mE). The organic phase was dried over anhydrous Na2SO4. The organic phase was concentrated under reduced pressure to give crude 271-3 (50 g, 43.4percent) as a solid.To a stirred solution of Int lc (4.2 kg, 19.63 mol), glycol (4.9 kg, 78.50 mol), NaHC0To a stirred solution of Int lc (4.2 kg, 19.63 mol), glycol (4.9 kg, 78.50 mol), NaHC0A mixture of 50 g of compound 3, 58.5 g of ethylene glycol, 59.5 Sodium bicarbonate solid, 750 ml of acetone was cooled to -15 to 10 ° C, Then, 100 g of a 36percent aqueous solution of sodium permanganate was slowly added thereto while maintaining the temperature, The reaction was terminated by adding dropwise for 1.5 hours.After completion of the reaction, Slowly dropping 0 25percent sodium bisulfite solution 75ml, Dropping process system temperature 0 ~ 5 , After stirring for 30 minutes, 12.5 g of CELITE in 25 ml of acetone was added and stirred for 1 hour. The filter cake was washed with acetone and the filtrate was combined. The acetone was removed by concentration under reduced pressure and extracted with ethyl acetate (250 ml * 3), washed with 250 ml of water The organic phase was distilled at atmospheric pressure and the ethyl acetate was replaced with toluene. The mixture was concentrated to a paste and 250 ml of heptane was added. The mixture was cooled to 25 to 28 ° C and stirred for 2 hours. The mixture was stirred at -10 to -5 ° C for 5 hours, filtered, percent Toluene in heptane and dried in vacuo at 48-50 ° C to give 37.2 g of a white crystalline solid 4 in 64.1percent yield with a purity of 98.9percent.Step B: Synthesis of 16d A solution of Int-16c (2.6 kg, 12.15 mol, 1.00 eq) in acetone (40 L) was treated with a solution of ethane-1, 2-diol (3.0 kg, 12.76 mol, 4.00 eq) and NaHCOTo a stirred solution of 269-2 (100 g, 0.47 mol) in acetone (2.0 L) was added KMnO4 (90 g, 0.57 mol) inportions at 0-5° C. The mixture was stirred at 0-5° C. for 2 h. The reaction was quenched using sat. sodiumsulfite solution (600 mL). After 2 h, a colorless suspension was formed. The solid was removed by filtration.The filter cake was washed with EA (300 mL). The filtrate was extracted with EA (3×300 mL). The organicphase was dried over anhydrous Na2SO4. The organic phase was concentrated under reduced pressure to givecrude 269-3 (50 g, 43.4percent) as a solidCrude 66-3 (1230 g, 5.74 mol) was dissolved in acetone (30 L) at 0-5° C. KMnOGeneral procedure: TEBAC (6 mmol) and KMnOA 50 mL of flask, equipped with magnetic stirrer, is charged with 2 mL of acetone, 214 mg (1 mmol) of compound 41, 65 mg of Et4NO Ac'4H2O, and 0.3 mL of ter/-butyl hydroperoxide (5 ~ 6 M in decane). After stirring at room temperature until the Et4NOAc a clear solution is obtained, the resulting solution is cooled in an ice bath and 5 mL of OsO4 (2.5 wtpercent in t-BuOH) is added in one portion. The solution immediately becomes brownish purple. After 1 h the ice bath is removed and the reaction mixture is allowed to warm to room temperature and stirred for 14 h. The rest of the procedure is done exactly the same way as described above. After flash column chromatography, 178 mg (72percent) of product is obtained as a solid. In an expanded 1H NMR, a tiny bump is observed at δ 1.26 indicating the presence of an isomer in less than 4percent in the product.; EXAMPLE 10 (2S, 3R)-3-[(4R)-2, 2-Dimethyl-fl , 3]dioxolan-4-yl]-2, 3-dihydroxy-2-methyl- propionic acid ethyl ester (42) t-Butylhydroperoxide as oxidant at 00C with Osmium catalyst. A 250 mL of flask, equipped with magnetic stirrer, is charged with 20 mL of acetone, 2.14 g (10 mmol) of compound 41, 650 mg of Et4NO Ac'4H2O, and 3 mL of hydroperoxide (5 ~ 6 M in decane). After stirring at room temperature until the Et4NOAc has dissolved, the resulting solution is cooled in an ice bath and 5 mL Of OsO4 (2.5 wtpercent in t-BuOH) is added in one portion. The solution immediately becomes brownish purple. The reaction mixture is then stirred at 0 0C for 6.5 h (monitored by TLC, hexanes: ethyl acetate = 4: 1 , Rf = 0.18). Ether (40 mL) is added at 0 0C and the resulting mixture is treated with 5 mL of freshly prepared 10 percent NaHSO3 solution in one portion. The ice bath is removed and stirring is continued for 1 h. EtOAc (100 mL) and H2O (50 mL) are added to the mixture. After separation of the layers, the aqueous phase is further extracted with EtOAc. The organic layer is washed with brine, dried (MgSO4) and concentrated. The residue is purified by a flash silica gel column chromatography with 20 percent EtOAc in hexanes to provide the product (2.16 g, 87percent) as a solid. No contamination of an isomer is detected in this product by vigorous 1H NMR analyses.To a solution of compound 41 (214 mg, 1 mmol) in a mixture of acetone (9 mL) and pyridine (1 mL) at 0 0C is added KMnO4 (158 mg, 1.0 mmol) and stirred at same temperature for 1 hr. After work up of the reaction mixture as above, 164 mg (67percent) of white solid which is practically pure product. Vigorous 1H NMR analyses reveal the crude white solid contains about 6percent of the diastere-omer of the titled compound.(2S, 3R)-3-[(4R)-2, 2-dimemyl-[l, 3] dioxolan-4-yl]-2, 3-dhydroxy-2- methyl-propionic acid ethyl ester (24)A suspension of 22 (10 kg, CAS Reg. No. 81997-76-4), ethylene glycol (11.6 kg), solid NaHCOA 100 mL round-bottomed flask, equipped with a magnetic stirrer, is charged with 5 mL of tert-b\x\y\ alcohol, 5 mL of water, and a mixture Of K3Fe(CN)6 (0.98 g), K2CO3 (0.41 g), and K2OsO2(OH)4 (3.2 mg). Stirring at room temperature produced two clear phases; the lower aqueous phase appears bright yellow. Methanesulfonamide (95 mg) is added at this point. The mixture is cooled to 0 0C whereupon some of salts precipitate out, 214 mg (1 mmol) of the compound 41 is added at once, and the heterogeneous slurry is stirred vigorously at 0 0C for 24 h. To the mixture is added solid sodium sulfite (1.5 g) while stirring at 0 0C, and then the mixture is allowed to warm to room temperature and stirred for 30-60 min. Ethyl acetate (10 mL) is added, and after separation of the layers, the aqueous phase is further extracted with EtOAc. The organic layer is dried over Na2SO4 and concentrated to dryness. The residue is purified by silica gel column chromatography with 20 percent EtOAc in hexanes to provide the product (190 mg, 77percent) as a solid, proton NMR indicates that the ratio of the desired product to its isomer is around 5:1. Recrystallization of the mixture with hexanes/ethyl acetate gave pure diol product (102 mg, 41percent from starting material) as a crystalline solid. The 1H NMR spectrum of this product is identical to that of an authentic specimen.To a stirred solution of compound 41 (214 mg, 0.1 mmol) in t-BuOH under argon was added a solution of 4-methylmorpholine N-oxide (0.47 mL, 50 wt percent solution in H2O) and water (0.2 mL). A 2.5 wtpercent solution of osmium tetraoxide in tert-bvAy\ alcohol (0.51 mL) is added, and the mixture is stirred for 5 h at room temperature in a water bath. The mixture is evaporated in vacuo to a syrup, which is azeotroped with H2O (3 x 10 mL) to remove 4-methylmorpholine. The residue is dried by addition and evaporation of EtOH (2 x 10 mL) to give a residue, which was purified by silica gel column chromatography with 20 percent EtOAc in hexanes to provide the desired product and its isomer (196 mg, 79percent) as a solid. Proton NMR indicates that the ratio of the desired product to its isomer is around 5:1. Recrystallization of the mixture from hexanes/ethyl acetate gives pure product (91mg, 37.4percent from starting material) as a crystalline solid. H NMR (DMSO-cfoe) δ 1.18 (t, J= 7.2 Hz, 3H, -OCH2CH3), 1.24 (s, 3H, CH3), 1.25 (s, 3H, CH3), 1.28 (s, 3H, 2-CH3), 3.67 (t, J= 7.2 Hz, 1 H), 3.85, 4.06 and 4.12 (m, 4 H), 4.97 (s, IH, 2- OH, D2O exchangeable), 5.14 (d, J= 7.6 Hz, 2-OH, D2O exchangeable).

Molecular Weight:248.27
XLogP3:-0.3
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:5
Exact Mass:248.12598835
Monoisotopic Mass:248.12598835
Topological Polar Surface Area:85.2
Heavy Atom Count:17
Complexity:290
Defined Atom Stereocenter Count:3
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes