COMPOUND USEFUL FOR MANUFACTURING SALACINOL, METHOD FOR MANUFACTURING THE COMPOUND, METHOD FOR MANUFACTURING SALACINOL, METHODS FOR PROTECTING AND DEPROTECTING DIOL GROUP, AND PROTECTIVE AGENT FOR DIOL GROUP

Abstract

An object of the present invention is to provide a novel compound useful for manufacturing salacinol, a method for manufacturing the compound, a method for manufacturing salacinol, methods for protecting and deprotecting a diol group, and a protective agent for a diol group. A compound represented by Formula (1) is a compound useful for manufacturing salacinol.

##STR00001##

(In the formula, each of R.sup.1a and R.sup.1b is a hydrogen atom or a hydroxy protective group; R.sup.2 is a hydroxy group or the like; and R.sup.3 is a hydroxy group or the like.)

Claims

1. A method for manufacturing salacinol, comprising: obtaining a compound represented by Formula (1b) by reacting a compound represented by Formula (1a) with a compound represented by Formula (7), ##STR00080## (in the formula, each of R.sup.1a and R.sup.1b are the same as or different from each other and each represent a hydrogen atom or a carboxy protective group), ##STR00081## (in the formula, each of R.sup.4a, R.sup.4b, and R.sup.4c are the same as or different from each other and each represent a hydrogen atom or a hydroxy protective group), and ##STR00082## (in the formula, each of R.sup.1a, R.sup.1b, R.sup.4a, R.sup.4b, and R.sup.4c has the same definition as described above); and then subjecting the compound represented by Formula (1b) to a deprotection reaction.

2. The manufacturing method according to claim 1, wherein each of R.sup.1a and R.sup.1b is a carboxy protective group, and each of R.sup.4a, R.sup.4b, and R.sup.4c is a hydrogen atom.

3. A method for manufacturing salacinol, comprising: obtaining a compound represented by Formula (1c) by reacting a compound represented by Formula (8) with a compound represented by Formula (9), ##STR00083## (in the formula, R.sup.5 is an aryl group which may be substituted), ##STR00084## (in the formula, R.sup.1a and R.sup.1b are the same as or different from each other and each represent a hydrogen atom or a carboxy protective group; R.sup.6 is a C.sub.1-6 alkyl group which may be substituted), and ##STR00085## (in the formula, each of R.sup.1a, R.sup.1b, and R.sup.5 has the same definition as described above); then obtaining a compound represented by Formula (1d) by subjecting the compound represented by Formula (1c) to a deprotection reaction, ##STR00086## (in the formula, each of R.sup.1a and R.sup.1b has the same definition as described above); then obtaining a compound represented by Formula (1a) by reacting the compound represented by Formula (1d) with a sulfur-containing compound and then subjecting the resulting compound to an oxidation reaction if necessary, ##STR00087## (in the formula, each of R.sup.1a and R.sup.1b has the same definition as described above); then obtaining a compound represented by Formula (1b) by reacting the compound represented by Formula (1a) with a compound represented by Formula (7), ##STR00088## (in the formula, R.sup.4a, R.sup.4b, and R.sup.4c are the same as or different from each other and each represent a hydrogen atom or a hydroxy protective group), and ##STR00089## (in the formula, each of R.sup.1a, R.sup.1b, R.sup.4a, R.sup.4b, and R.sup.4c has the same definition as described above); and then subjecting the compound represented by Formula (1b) to a deprotection reaction.

4. The manufacturing method according to claim 3, wherein R.sup.5 is a phenyl group which may be substituted.

5. The manufacturing method according to claim 3, wherein each of R.sup.1a and R.sup.1b is a carboxy protective group, and each of R.sup.4a, R.sup.4b, and R.sup.4c is a hydrogen atom.

6. A compound represented by Formula (7a), ##STR00090## (in the formula, R.sup.4ba is a p-toluoyl group).

7. A method for manufacturing a compound represented by Formula (7b), comprising: ##STR00091## obtaining a compound represented by Formula (12) by reacting a compound represented by Formula (10) with a compound represented by Formula (11), ##STR00092## (in the formula, R.sup.7 is a C1-3 alkyl group which may be substituted),
R.sup.4ba-L.sup.1   (11) (in the formula, R.sup.4ba is a p-toluoyl group; and L.sup.1 is a leaving group), and ##STR00093## (in the formula, each of R.sup.4ba and R.sup.7 has the same definition as described above); then obtaining a compound represented by Formula (7a) by reacting the compound represented by Formula (12) with an acid and then subjecting the resulting compound to a reduction reaction, ##STR00094## (in the formula, R.sup.4ba has the same definition as described above); and then subjecting the compound represented by Formula (7a) to a deprotection reaction.

8. A method for manufacturing a compound represented by Formula (7b), comprising: ##STR00095## obtaining a compound represented by Formula (15) by reacting a compound represented by Formula (13) with a compound represented by Formula (14), ##STR00096## (in the formula, R.sup.7 is a C.sub.1-3 alkyl group which may be substituted),
R.sup.8-L.sup.2   (14) (in the formula, R.sup.8 is a C.sub.1-3 alkylsulfonyl group which may be substituted or an arylsulfonyl group which may be substituted; and L.sup.2 is a leaving group), and ##STR00097## (in the formula, each of R.sup.7 and R.sup.8 has the same definition as described above); then obtaining a compound represented by Formula (17) by reacting the compound represented by Formula (15) with a compound represented by Formula (16),
R.sup.8-S.sup.−K.sup.+  (16) (in the formula, R.sup.9 is an acyl group which may be substituted), and ##STR00098## (in the formula, each of R.sup.7, R.sup.8, and R.sup.9 has the same definition as described above); then obtaining a compound represented by Formula (18) by reacting the compound represented by Formula (17) with a base, ##STR00099## (in the formula, each of R.sup.7 and R.sup.8 has the same definition as described above); then obtaining a compound represented by Formula (10) by subjecting the compound represented by Formula (18) to a deprotection reaction, ##STR00100## (in the formula, R.sup.7 has the same definition as described above); then obtaining a compound represented by Formula (12) by reacting the compound represented by Formula (10) with a compound represented by Formula (11),
R.sup.4ba-L.sup.1   (115) (in the formula, R.sup.4ba is a p-toluoyl group; and L.sup.1 is a leaving group), and ##STR00101## (in the formula, each of R.sup.4ba and R.sup.7 has the same definition as described above); then obtaining a compound represented by Formula (7a) by reacting the compound represented by Formula (12) with an acid and then subjecting the resulting compound to a reduction reaction. ##STR00102## (in the formula, R.sup.4ba has the same definition as described above); and then subjecting the compound represented by Formula (7a) to a deprotection reaction.

9. A method for protecting a 1,2-diol group or a 1,3-diol group, comprising reacting a 1,2-diol group or a 1,3-diol group with a group represented by Formula (19) in the presence of a base, ##STR00103## (in the formula, R.sup.1a and R.sup.1b are the same as or different from each other and each represent a hydrogen atom or a carboxy protective group; and * is a binding position).

10. A method for protecting a 1,2-diol group or a 1,3-diol group, comprising manufacturing a compound represented by Formula (21) by reacting a 1,2-diol group or a 1,3-diol group of a compound represented by Formula (20) with a compound represented by Formula (9) in the presence of a base,
HO—Y.sup.1—OH   (20) (in the formula, Y.sup.1 is a C.sub.2-3 alkylene group which may be substituted), ##STR00104## (in the formula, each of R.sup.1a and R.sup.1b are the same as or different from each other and each represent a hydrogen atom or a carboxy protective group; and R.sup.6 is a C.sub.1-6 alkyl group which may be substituted), and ##STR00105## (in the formula, each of R.sup.1a, R.sup.1b, and Y.sup.1 has the same definition as described above).

11. A protective agent for a 1,2-diol group or a 1,3-diol group, comprising a compound represented by Formula (9), ##STR00106## (in the formula, R.sup.1a and R.sup.1b are the same as or different from each other and each represent a hydrogen atom or a carboxy protective group; and R.sup.6 is a C.sub.1-6 alkyl group which may be substituted).

12. A method for deprotecting a protected 1,2-diol group or 1,3-diol group, comprising reacting a 1,2-diol group or a 1,3-diol group protected with a group represented by Formula (19) with a base, ##STR00107## (in the formula, R.sup.1a and R.sup.1b are the same as or different from each other and each represent a hydrogen atom or a carboxy protective group; and * is a binding position).

13. A method for deprotecting a protected 1,2-diol group or 1,3-diol group, comprising manufacturing a compound represented by Formula (20) by reacting a compound which is represented by Formula (21) and has a protected 1,2-diol group or a protected 1,3-diol group with a base, ##STR00108## (in the formula, R.sup.1a and R.sup.1b are the same as or different from each other and each represent a hydrogen atom or a carboxy protective group; and Y.sup.1 is a C.sub.2-3 alkylene group which may be substituted), and
HO—Y.sup.1—OH   (20) (in the formula, Y.sup.1 has the same definition as described above).

Description

EXAMPLES

[0404] Unless otherwise specified, as a carrier for silica gel column chromatography, an FR-260 HI-FLASTM COLUMN manufactured by YAMAZEN CORPORATION and WAKOGEL C-200 manufactured by Wako Pure Chemical Industries, Lt. was used.

[0405] A mixing ratio in an eluant is volume ratio. For example, “hexane/ethyl acetate=90/10 to 50/50” means an eluant of 90% hexane/10% ethyl acetate is finally changed to an eluant of 50% hexane/50% ethyl acetate.

[0406] An NMR spectrum was measured using tetramethylsilane as an internal standard and using BRUKER AV300 (Bruker Corporation) or JNM-AL400 model (JEOL Ltd.), and all of the δ values were expressed using ppm.

[0407] Each abbreviation in each example means the following.

[0408] Ac: acetyl

[0409] Bn: benzyl

[0410] Et: ethyl

[0411] Me: methyl

[0412] Ph: phenyl

[0413] PMB: 4-methoxybenzyl

[0414] Tol: p-toluoyl

[0415] Ts: 4-methylbenzenesulfonyl

[0416] DMSO-D.sub.6: deuterated dimethyl sulfoxide

[0417] pyridine-D.sub.5: deuterated pyridine

[0418] HPLC: high performance liquid chromatography

Reference Example 1

[0419] ##STR00055##

[0420] 2.00 g of 60% sodium hydride was added to 15 mL of a N,N,-dimethylformamide solution containing 1.50 g of (2R,3S,4S)-2-(hydroxymethyl)tetrhydrothiophene-3,4-diol at 0° C., and the resulting mixture was stirred for 1 hour at a temperature of equal to or lower than 5° C. Then, 4.50 mL of benzyl bromide was added thereto at 0° C., followed by stirring for 3 hours at 25° C. Ethyl acetate and water were added to the reaction mixture. An organic layer was collected by separation, washed with a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate, and the solvent was distilled away under reduced pressure. The obtained residue was purified by column chromatography (hexane/ethyl acetate =95/5 to 86/14), thereby obtaining 2.31 g of (2R,3S,4S)-3,4-bis(benzyloxy)-2-((benzyloxy)methyl)tetrahydrothiophene as a colorless oily substance.

[0421] .sup.1H-NMR (CDCl.sub.3) δ values: 2.90 (1H, dd, J=4.8, 11.4 Hz), 3.04 (1H, M, J=5.0, 11.4 Hz), 3.47-3.59 (2H, m), 3.69 (1H, t, J=7.8 Hz), 4.10-4.21 (2H, m), 4.45-4.61 (6H; m), 7.25-7.35 (15H, m).

Reference Example 2

[0422] ##STR00056##

[0423] 1.49 g of 60% sodium hydride was added to 10 mL of a N,N-dimethylformamide solution containing 1.12 g of (2R,3S,4S)-2-(hydroxymethyl)tetrahydrothiophene-3,4-diol at 0° C., and the resulting mixture was stirred for 30 minutes at a temperature of equal to or lower than 5° C. then, 3.86 mL of 4-methoxybenzyl chloride was added thereto at 0° C., followed by stirring for 6 hours at 25° C. Ethyl acetate and water were added to the reaction mixture. An organic layer was collected by separation, washed with a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate, and the solvent was distilled away under reduced pressure. The obtained residue was purified by column chromatography (hexane/ethyl) acetate=95/5 to 86/14), thereby obtaining 1.93 g of (2R,3S,4S)-3,4-bis((4-methoxybenzyl)oxy)-2-(((4-methoxybenzyl)oxy)methyl)tetrahydrothiophene as a colorless oily substance.

[0424] .sup.1H-NME (CDCl.sub.3) δ values: 2.86 (1H, dd, J=4.8, 11.4 Hz), 3.03 (1H, dd, J=5.2, 11,4 Hz), 3.42-3.52 (2H, m), 3.64 (1H, dd, J=7.2, 8.1 Hz), 3.79-3.81 (9H, m), 4.03-4.16 (2H, m), 4.39-4.52 (6H, m), 6.84-6.87 (6H, m), 7.18-7.25 (6H, m).

Example 1

[0425] ##STR00057##

[0426] 1.1 g of tert-butoxypotassium was added to 200 mL of a tetrahydroguran solution containing 20.0 g of (4S,5R)-4-(hydroxymethyl)-2-phenyl-1,3-dioxan-5-ol and 18.2 g of dimethyl methoxymethylene malonate at 25020 C., and the resulting mixture was stirred for 1 hour at 25° C. Toluene was added to the reaction mixture, tetrahydrofuran was distilled away under reduced pressure, and then ethyl acetate and water were added thereto. An organic layer was collected by separation, washed sequentially with water and then with a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate, and the solvent was distilled away under reduced pressure. The obtained residue was recrystallized from methanol, thereby obtaining 21.3 g of dimethyl 2-((4aS,8aR)-6-phenyltetrahydro[1,3]dioxino[5,4-d][1,3]dioxin-2-yl)malonate as a white solid. 1H-NMR (CDCl3) δ values: 3.73-3.81 (11H, m), 4.23-4.31 (2H, m), 5.30 (1H, d, J=7.8 Hz), 5.60 (1H, s), 7.35-7.39 (3H, m), 7.44-7.50 (2H, m).

Example 2

[0427] ##STR00058##

[0428] 1.24 g of 20% palladium hydroxide/carbon was added to 70 mL of an ethyl acetate solution containing 20.4 g of dimethyl 2-((4aS,8aR)-6-phenyltetrahydro[1,3]dioxino[5,4-d][1,3]dioxin-2-yl)malonate at 25° C., and the resulting mixture was stirred for 4 hours in a hydrogen atmosphere (5 MPa). After insoluble matters were removed by filtration, the solvent was distilled away under reduced pressure, thereby obtaining 15.7 g of dimethyl 2-((4R,5S)-5-hydroxy-4-(hydroxymethyl)-1,3-dioxan-2-yl)malonate as a colorless oily substance.

[0429] .sup.1H-NMR (CDCl.sub.3) δ values: 2.40 (1H, s), 2.70 (1H, s), 3.44-3.56 (2H, m), 3.68 (1H, d, J=7.2 Hz), 3.76-3.85 (9H, m), 4.11-4.21 (1H, m), 5.15 (1H, d, J=7.2 Hz).

Example 3

[0430] ##STR00059##

[0431] 112 mL of triethylamine was added to 800 mL of a methylene chloride solution containing 53.0 g of dimethyl 2-((4R,5S)-5-hydroxy-4-(hydroxymethyl)-1,3-dioxan-2-yl)malonate of a temperature of equal to or lower than −5° C., and than 500 mL of a methylene chloride solution containing 21.8 mL of thionyl chloride was added dropwise thereto at a temperature of equal to or lower than −5° C. The reaction mixture was stirred for 20 minutes at a temperature of equal to or lower than 5° C., and then water was added thereto. An organic layer was collected by separation and washed sequentially with 1 mol/L hydrochloric acid, water, and then a saturated aqueous sodium hydrogen carbonate solution, and the solvent vas distilled away under reduced pressure.

[0432] A mixed solution of 265 mL of methylene chloride containing the obtained residue and 265 mL of acetonitrile was added dropwise to 530 mL of water containing 159 g of sodium periodate and 1.25 g of a ruthenium (III) chloride n-hydrate at 0° C., followed by stirring tor 20 minutes. Ethyl acetate was added to the reaction mixture. An organic layer was collected by separation, washed sequentially with water, a 10% aqueous sodium thiosulfate solution, and then a saturated aqueous sodium chloride solution, and anhydrous magnesium sulfate and silica gel were added thereto, followed by stirring for 5 minutes. After insoluble matters were removed by filtration, the solvent was distilled away under reduced pressure, and the obtained residue was recrystallized from methanol and a water, thereby obtaining 42.3 g of dimethyl 2-((4aR,8aS)-2,2-dioxidotetrahydro[1,3]dioxino[5,4-d][1,3,2]dioxathiin-6-yl)molonate as a

[0433] .sup.1H-NMR (CDCl3) δ values: 3.70 (1H, d, J=7.8 Hz), 3.77 (3H, s), 3.78 (3H, s), 3.82 (1H, d, J=10.5 Hz), 4.01-4.11 (1H, m), 4.31 (1H, dd, J=5.0, 10.5 Hz), 4.56 (1H, dd, J=5.0, 10.5 Hz), 4.54-4.75 (2H, m), 5.27 (1H, d, J=7.8 Hz).

Example 4

[0434] ##STR00060##

[0435] 31 μL, of 2,6-lutidine was added to 1.5 mL of an acetone solution containing 500 mg of (2R,3S,4S)-2-(hydroxymethyl)tetrahydrothiophene-3,4-diol and 1.14 g of dimethyl 2-((4aR,8aS)-2,2-dioxidotetrahydro[1,3]dioxino[5,3-d][1,3,2]dioxathiin-6-yl)malonate at 25° C., followed by stirring for 13 hours at 70° C. The reaction mixture was cooled to room temperature, acetone was added thereto, and solids were collected by filtration, thereby obtaining 1.20 g of (4S,5S)-4-(((2R,3S,4S)-3,4-dihydroxy-2-(hydroxymethyl)tetrahydro-1H-thiophen-1-ium-1-yl) methyl-2-(1,3-dimethoxy-1,3-dioxopropan-2-yl)-1,3-dioxan-5-yl sulfate as a white solid.

[0436] As a result of measuring .sup.1H-NMR and HPLC, it was confirmed that a ratio of trans/cis was 78/22.

[0437] .sup.1H-HMR (DMSO-D.sub.6) δ values: 3.56-3.63 (2H, m), 3.62-3.73 (8H, m) 3.42-4.08 (6H, m), 4.14 (1H, dd, J=5.3, 10.2 Hz), 4.22-4.29 (2H, m), 4.47-4.53 (1H, m), 5.21 (1H, d, J=7.5 Hz), 5.57 2H, m), 6.13 (2H, m).

Example 5

[0438] ##STR00061##

[0439] 756 μL of diethylamine was added to a mixed solution of 14.5 mL of water and 14.5 mL of ethyl acetate containing 2.90 g of (4S,5S)-4-(((2R,3S,4S)-3,4-dihydroxy-2-(hydroxymethyl)tetrahydro-1H-thiophen-1-ium-1-yl) methyl-2-(1,3-dimethoxy-1,3-dioxopropan-2-yl)-1,3-dioxan-5-yl sulfate (trans/cis=78/22) at 25° C., followed by stirring for 50 minutes at 25° C. An aqueous layer was collected by separation and washed with ethyl acetate, and the solvent was distilled away under reduced pressure. The obtained residue was recrystallized from methanol, thereby obtaining 1.05 g of (2S,3S)-4-((1S,2R,3S,4S)-3,4-dihydroxy-2-(hydroxymethyl)tetrahydro-1H-thiophen-1-ium-1-yl)-1,3-dihydroxybutan-2-yl sulfate (salacinol) as a white solid.

[0440] .sup.1H-NMR (pyridine-D.sub.5) δ values: 4.32-4.39 (3H, m), 4.51-4.66 (5H, m), 4.75-4.82 (1H, m), 4.91-5.05 (1H, m), 5.09-5.14 (2H, m), 5.23-5.27 (1H, m).

[0441] 220 μL of triethylamine was added to a mixed solution of 2.5 mL of water and 2.5 mL of methanol containing 500 mg of (4S,5S )-4-(((2R,3S,4S)-3,4-dihydroxymethyl)tetrahydro-1H-thiophen-1-ium-1-yl) methyl-2-(1,3-dimethoxy-1,3-dioxopropan-2-yl)-1,3-dioxan-5-yl sulfate (trans/cis=78/22) at 25° C. followed by stirring for 5 hours at 25° C. Ethyl acetate was added to the reaction mixture. An aqueous layer was collected by separation and washed with ethyl acetate, and the solvent was distilled away under reduced pressure.

[0442] As a result of measuring the obtained residue by HPLC, it was confirmed that salacinol was generated, and the reaction rate was 97%.

[0443] (5-3)

[0444] 220 μL of propyl amine was added to a mixed solution of 2.5 mL of water and 2.5 mL of toluene containing 500 mg of (4S,5S)-4-(((2R,3S,4S)-3,4-dihydroxy-2-yl)-1,3-dioxan-5-yl sulfate (trans/cis=78/22) at 25° C., followed by stirring for 1 hour at 25° C. Toluene was added to the reaction mixture. An aqueous layer was collected by separation, and the solvent was distilled away under reduced pressure.

[0445] As a result of measuring the obtained residue by HPLC, it was confirmed that salacinol was generated, and the reaction rate was 96%.

[0446] (5-4)

[0447] 212 μL of dibutylamine was added to a mixed solution of 2.5 mL of water and 2.5 mL of toluene containing 300 mg of (4S,5S)-4-(((2R,3S,4S)-3,4-dihydroxy-2-(hydroxyethyl)tetrahydro-1H-thiophen-1-ium-1-yl) methyl-2-(1,3-dimethoxy-1,3-dioxopropan-2-yl)-1,3-dioxan-5-yl) sulfate (trans/cis=78/22) at 25° C., followed by stirring for 4 hours at 25° C. Toluene was added to the reaction mixture. An aqueous layer was collected by separation, and the solvent was distilled away under reduced pressure.

[0448] As a result of measuring the obtained residue by HPLC, it was confirmed that salacinol was generated, and the reaction rate was 85%.

[0449] (5-5)

[0450] 10 mL of an aqueous solution containing 1 g of (4S,5S)-4-(((2R,3S,4S)-3,4-dihydroxy-2-(hydroxymethyl)tetrahydro-1H-thiophen-1-ium-1-yl) methyl-2-(1,3-dimethoxy-1,3-dioxopropan-2-yl)-1,3-dioxan-5-yl sulfate (trans/cis=78/22) was stirred for 8 hours at 70° C., and then the solvent was distilled away under reduced pressure. 203 μL of pyridine and 287 μL of aniline were added to a mixed solution of 5 mL of water and 5 mL of methanol containing the obtained oily substance at 25° C., followed by stirring for 13 hours at 50° C. Toluene was added to the reaction mixture. An aqueous layer was collected by separation and washed with ethyl acetate, and the solvent was distilled away under reduced pressure.

[0451] The obtained residue was recrystallized from methanol, thereby obtaining 485 mg of salacinol as a white solid.

Example 6

[0452] ##STR00062##

[0453] 31 μL of 2,6-lutidine was added to 1.5 mL of acetone solution containing 1.24 g of (2R,3S,4S)-3,4-bis(benzloxy)-2-((benzyloxy)methyl)tetrahydrothiophene and 1.01 g of dimethyl 2-(4aR,8aS)-2,2-dioxidotetrahydro[1,3]dioxino[5,4-d][1,3,2]dioxathiin-6-yl)malonate at 25° C., followed by stirring for 24 hours at 70° C. The reaction mixture was cooled to room temperature, and the solvent was distilled away under reduced pressure. The obtained residue was purified by column chromatography (chloroform/methanol=99/1 to 95/5), thereby obtaining 1.32 g of (4S,5S)-4-(((1S,2R,3S,4S)-3,4-bis(benzyloxy)-2-((benzyloxy)methyl)tetrahydro-1H-thiophen-1ium-1-yl) -ium-1-yl)methyl)-2-(1,3-dimethoxy-1,3-dioxopropan-2-yl)-1,3-dioxan-5-yl sulfate as a colorless oily substance.

[0454] .sup.1H-NMR (DMSO-D.sub.6) δ values: 3.56-3.66 (7H, m), 3.72-376 (2H, m), 3.88-4.16 (7H, m), 4.24-4.38 (2H, m), 4.51-4.64 (7H, m), 4.76-4.79 (1H, m), 5.17 (1H, d, J=7.2 Hz), 7.33-7.37 (15H, m).

Example 7

[0455] ##STR00063##

[0456] 73 μL of diethylamide was added to 4.4 mL of a methanol solution containing 440 mg of (4S,5S)-4-(((1S,2R,3S,4S)-3,4-bis(benzyloxy)-2-((benzyloxy)methyl)tetrahydro-1H-thiophen-1-ium-1yl)methyl)-2-(1,3-dimethoxy-1,3-dioxopropan-2-yl)-1,3-dioxan-5-yl sulfate at 25° C., followed by stirring for 1 hour at 25° C. The solvent of the reaction mixture was distilled away under reduced pressure, and the obtained residue was purified by column chromatography (chloroform/methanol=100/0 to 92/8), thereby obtaining 240 mg of (2S,3S)-4-((1R,2R,3S,4S)-3,4-bis(benzyloxy)-2-((benzyloxy)methyl)tetrahydro-1H-thiophen-1-ium-1-yl)-1,3-dihydroxybutan-2-yl sulfate as a white solid.

[0457] .sup.1H-NMR (DMSO-D.sub.6) δ values: 3.61-3.65 (2H, m), 3.74-4.05 (6H, m) 4.09-4.14 (1H, m), 4.17-4.23 (1H, m), 4.36-4.41 (1H, m), 4.50-4.80 (9H, m), 6.01 (1H, d, J=6.0 Hz), 7.23-7.39 (15H, m).

Example 8

[0458] ##STR00064##

[0459] 24 mg of 20%: palladium hydroxide/carbon was added to 1 mL of acetic acid solution containing 240 mg of (2S,3S)-4-((1R,2R,3S,4)-3-bis(benzyloxy)-2-((benzyloxy)methyl)tetrahydro-1H-thiophen-1-ium-1-yl)-1,3-dihydroxybutan-2-yl sulfate at 25° C., followed by stirring for 2 hours at 50° C. in a hydrogen atmosphere. The reaction mixture was cooled to room temperature, and insoluble matters were removed by filtration.

[0460] As a result of measuring .sup.1H-NMR and HPLC, it was confirmed that the raw material disappeared, and salacinol was generated.

Example 9

[0461] ##STR00065##

[0462] 18 μL of 2,6-lutidine was added to 1 mL of an acetone solution containing 1.00 g of (2R,3S,4S)-3,4-bis((4-methoxybenzyl)oxy)-2-(((4-methoxybenzyl)oxy)methyl)tetrahydrothiophene and 671 mg of dimethyl 2-((4aR,8aS)-2,2-dioxidotetrahydro[1,3]dioxino[5,4-d][1,3,2]dioxathiin-6-yl)malonate at 25° C., followed by stirring for 13 hours at 70° C. The reaction mixture was cooled to room temperature, and the solvent was distilled away under reduced pressure. The obtained residue was purified by column chromatography (chloroform/methanol=90/10), thereby obtaining 1.10 g of (4S,5S)-4-(((1S,2R,3S,4S)-3,4-bis((4-methoxybenzyl)oxy)-2-(((4-methoxybenzyl)oxy)methyl) tetrahydro-1H-thiophen-1-ium-1-yl)methyl)-2-(1,3-dimethoxy-1,3-dioxopropan-2-yl)-1,3-dioxan-5-yl sulfate as a white solid.

[0463] .sup.1H-NMR (DMSO-D.sub.6) δ values: 3.52-4.17 (25H, m), 4.21-4.28 (2H, m), 4.41-4.58 (7H, m), 4.64-4.69 (1H, m), 5.16 (1H, d, J=7.5 Hz), 6.88-6.93 (6H, m), 7.16-7.28 (6H, m).

Example 10

[0464] ##STR00066##

[0465] 74 μL of diethylamine was added to 5.0 mL of a methanol solution containing 500 mg of (4S,5S)-4-(((1S,2R,3S,4S)-3,4-bis((4-methoxybenzyl)oxy-2-(((4-methoxybenzyl)oxy)methyl) tetrahydro-1H-thiophen-1-ium-1-yl)methyl)-2-(1,3-dimethoxy-1,3-dioxopropan-2-yl)-1,3-dioxan-5-yl sulfate at 25° C., followed by stirring for 3 hours at 25° C. The solvent of the reaction mixture was distilled away under reduced pressure, and the obtained residue was purified by column chromatography (chloroform/methanol=100/0 to 94/6), thereby obtaining 300 mg of (2S,3S)-4-((1R,2R,3S,4S)-3,4-bis((4-methoxybenzyl)oxy)-2-(((4-methoxybenzyl)oxy)methyl)tetrahydro-1H-thiophen-1-ium-1-yl)-1,3-dihydroxybutan-2-yl sulfate as a white solid.

[0466] .sup.1H-NMR (DMSO-D.sub.6) δ values: 3.49-3.99 (17H, m) 4.06-4.21 (2H, m) 4.28-4.31 (1H, m), 4.38-4.66 (8H, m), 4.76-4.79 (1H, m), 6.00 (1H, d, J=6.0 Hz), 6.30-6.93 (6H, m), 7.16-7.28 (6H, m).

Example 11

[0467] ##STR00067##

[0468] A mixed solution of 1.2 mL of trifluoroacetic acid and 0.2 L of water containing 300 mg of (2S,3S)-4-((1R,2R,3S,4S)-3,4-bis((4-methoxybenzyl)oxy)-2-(((4-methoxybenzyl)oxy)methyl)tetrahydro-1H-thiophen-1-ium-1-yl)-1,3-dihydroxybutan-2-yl sulfate was stirred for 2 hours at 25° C.

[0469] As a result of measuring .sup.1H-NMR and HPLC, it was confirmed that the raw material disappeared, and salacinol was generated.

Example 12

[0470] ##STR00068##

[0471] 267 mg of tert-butoxypotassium was added to 50 mL of a tetrahydrofuran solution containing 5.00 g of (4S,5R)-4-(hydroxymethyl)-2-phenyl-1,3-dioxan-5-ol and 5.7 g diethyl ethoxymethylene malonate at 25° C., followed by stirring for 1 hour at 25° C. Toluene was added to the reaction mixture, tetrahydrofuran was distilled away under reduced pressure, and then ethyl acetate and water were added thereto. An organic layer was collected by separation, washed sequentially with water and a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate, and the solvent was distilled away under reduced pressure. The obtained residue was purified by column chromatography (hexane/ethyl acetate=16/84 to 33/67), thereby obtaining 3.54 g of diethyl 2-((4aS,8aR)-6-phenyltetrahydro[1,3]dioxino[5,4-d][1,3]dioxin-2-yl)malonate as a white solid.

[0472] 1H-NMR (CDCl3) δ values: 1.24-1.31 (6H, m) 3.65 (1H, d, J=7.8 Hz), 3.65-3.82 (4H, m), 4.19-4.27 (6H, m), 5.30 (1H, d, J=7.8 Hz), 5.61 (1H, s), 7.35-7.39 (3H, m), 7.45-7.49 (2H, m).

Example 13

[0473] ##STR00069##

[0474] 800 μL of a 0.5 mol/L hydrochloric acid/methanol solution to 18 mL of a methanol solution containing 3.54 g of diethyl 2-((4aS,8aR)-6-phenyltetrahydro[1,3]dioxino[5,4][1,3]dioxin-2-yl)malonate at 25° C., followed by stirring for 3 hours at 25° C. 50 μL of triethylamine was added to the reaction mixture, and the solvent was distilled away under reduced pressure. The obtained residue was purified by column chromatography (hexane/ethyl acetate=33/67 to 0/100), thereby obtaining 2.45 g of diethyl 2-((4R,5S)-5-hydroxy-4-(hydroxymethyl)-1,3-dioxan-2-yl)malonate as a colorless oily substance.

[0475] .sup.1H-NMR (CDCl.sub.3) δ values: 1.24-1.30 (6H, m) 2.37 (1H, s), 2.75 (1H, s), 3.44-3.56 (2H, m), 3.63 (1H, d, J=7.5 Hz), 3.78-3.86 (3H, m) 4.16-4.26 (5H, m), 5.15 (1H, d, J=7.5 Hz).

Example 14

[0476] ##STR00070##

[0477] 4.44 mL of triethylamine was added to 40 mL of a methylene chloride solution containing 2.45 g of diethyl 2-((4R,5S)-5-hydroxy-4-(hydroxymethyl)-1,3-dioxan-2-yl)malonate at a temperature of equal to or lower than −5 °C. and then 21 mL of a methylene chloride dilution containing 913 μL of thionyl chloride was added dropwise thereto at a temperature of equal to or lower than −5° C. The reaction mixture was stirred for 20 minutes at a temperature of equal to or lower than 5° C., water was added thereto. An organic layer was collected by separation and then washed sequentially with 1 mol/L hydrochloric acid, a saturated aqueous sodium hydrogen carbonate solution, and a saturated aqueous sodium chloride solution, and the solvent was distilled away under reduced pressure.

[0478] A mixed solution of 10 mL of methylene chloride and 10 mL of acetonitrile containing the obtained residue was added dropwise to 25 mL of an aqueous solution containing 6.64 g of sodium periodate and 52.2 mg of ruthenium (III) chloride n-hydrate at 0° C., followed by stirring for 20 minutes. Ethyl acetate was added to the reaction mixture. An organic layer was collected by separation and washed sequentially with water, a 10% aqueous sodium thiosulfate solution, and a saturated aqueous sodium chloride solution, and anhydrous magnesium sulfate and silica gel were added thereto, followed by stirring for 5 minutes. After insoluble matters were removed by filtration, the solvent was distilled away under reduced pressure. The obtained residue was purified by column chromatography (hexane/ethyl acetate=84/16 to 60/40), thereby obtaining 2.10 g of diethyl 2-((4aR,8aS)-2,2-dioxidotetrahydro[1,3]dioxino[5,4-d][1,3,2]dioxathiin-6-yl)malonate as a white solid.

[0479] .sup.1H-NMR (CDCl.sub.3) δ values: (1.25-1.30 (6H, m), 3.65 (1J, d, J=7.8 Hz), 3.80 (1H, dd, J=10.5 10.5 Hz), 4.02-4.11 (1H, m), 4.18-4.35 (5H, m), 4.52-4.57 (1H, m), 4.63-4.72 (2H, m), 5.26 (1H, d, J=7.8 Hz).

Example 15

[0480] ##STR00071##

[0481] 31 μL of 2,6-lutidine was added to 1,5 mL of an acetone solution containing 500 mg of (2R,3S,4S)-2-(hydroxymethyl)tetrahydrothiophene-3,4-diol and 1.24 g of diethyl 2-((4aR,8aS)-2,2-dioxidotetrahydro[1,3]dioxino[5,4-d][1,3,2]dioxathiin-6-yl)malonate at 25° C., followed by stirring for 13 hours at 70° C. The reaction mixture was cooled to room temperature, acetone was added thereto, and solids were collected by filtration, thereby obtaining 1.01 g of (4S,5S)-2-(1,3-diethoxy-1,3-dioxopropan-2-yl)-4-(((2R,3S,4S)-3,4-dihydroxy-2-(hydroxymethyl)tetrahydro-1H-thiophen-1-ium-1-yl)methyl)-1,3-dioxan-5-yl sulfate as a white solid. As a result of measuring .sup.1H-NMR, it was confirmed that a ratio of trans/cis in this compound was 81/19.

[0482] .sup.1H-NMR (DMSO-D.sub.6) δ values: 1.19 (6H, dd, J=7.0, 13.6 Hz), 3.54-4.21 (17H, m), 4.45-4.51 (1H, m), 5.20 (1H, m), 5.68-5.71 (1H, m), 6.12-6.14 (2H, m).

Example 16

[0483] ##STR00072##

[0484] 123 μL of diethylamine was added to a mixed solution of 2.5 mL of water and 2.5 mL of ethyl acetate containing 500 mg of (4S,5S)-2-(1,3-diethoxy-1,3-dioxopropan-2-yl)-4-(((2R,3S,4S)-3,4-dihydroxy-2-(hydroxymethyl)tetrahydro-1H-thiophen-1-ium-1-yl)methyl)-1,3-dioxan-5-yl sulfate (trans/cis=81/19) at 25° C., followed by stirring for 9 hours at 25° C. An aqueous layer was collected by separation and washed with ethyl acetate, and the solvent was distilled away under reduced pressure.

[0485] As a result of measuring .sup.1H-NMR and HPLC of the obtained residue, it was confirmed that salacinol was generated, and the reaction rate was 97%.

Example 17

[0486] ##STR00073##

[0487] 22.0 mL of acetyl chloride was added dropwise to 840 mL of a methanol solution containing 120 g of (3R,4R,5R)-5-(hydroxymethyl)tetrahydrofuran-2,3,4-triol at a temperature of equal to or lower than 10° C., followed by stirring for 2 hours at a temperature of 20° C. to 30° C. 63 mL of a 28% sodium methoxide methanol solution was added to the reaction mixture, methanol was distilled away under reduced pressure, arte 800 mL of acetonitrile and 480 g of p-toluenesulfonyl chloride were added thereto. In a state where the internal temperature was kept at a temperature of equal to or lower than 25° C., a mixture of 323 mL of triethylamine and 25.2 mL of N-methylimidazole was added dropwise thereto, followed by stirring for 2.5 hours at 30° C. 900 mL of water was added to the reaction mixture, followed by stirring for 2 hours at 30° C., and ethyl acetate was added thereto. An organic layer was collected by separation, washed with a 25% aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. 1.9 L of ethanol was added to the obtained residue and dissolved by heating, and the resulting mixture was crystallized while being cooled. 800 mL of methanol was added thereto at an internal temperature of 35° C., followed by stirring for 2 hours at 25 °C. Solids were collected by filtration, thereby obtaining 47 g of (3R,4S,5R)-2-methoxy-5-(((4-methylphenyl)sulfonyloxy)methyl)tetrahydrofuran-3,4-diyl bis(4-methylbenzenesulfonate) as a white solid.

[0488] .sup.1H-NMR (CDCl.sub.3) δ values: 7.77-7.64 (6H, m), 7.41-7.32 (6H, m), 5.04 (0.26H, t, J=6.9 Hz), 4.79 (0.74H, dd, J=1.2, 6.0 Hz), 4.80-4.65 (2H, m), 4.43 (0.74H, m), 4.34 (0.26H, m), 4.25-4.14 (0.26H, m), 4.12-4.04 (1.74H, m), 3.21 (0.78H, s), 3.16 (2.22H, s), 2.48-2.45 (3H, m).

Example 18

[0489] ##STR00074##

[0490] 65.6 g of S-potassium thioacetate was added to 585 mL of a N,N-dimethylformamide solution containing 200 g of (3R,4S,5R)-2-methoxy-5-(((4-methylphenyl)sulfonyloxy)methyl)tetrahydrofuran-3,4-diyl bis(4-methylbenzenesulfonate) in a nitrogen atmosphere, followed by stirring for 2 hours at 70° C. the reaction mixture was cooled to room temperature, and water, a 25% aqueous sodium chloride solution, and ethyl acetate were added thereto. An organic layer was collected by separation, washed sequentially with a 7.5% aqueous sodium hydrogen carbonate solution, 1 mol/L hydrochloric acid, and a 25% aqueous sodium chloride solution, treated with 3 g of activated carbon, and then dried over anhydrous magnesium sulfate, and the solvent was distilled away under reduced pressure. As a result, 161.5 g of S-(((2S,3S,4R)-5-methoxy-3,4-bis((4-methylphenyl)sulfonyloxy)tetrahydrofuran-2-yl)methyl) ethanethioate as a reddish brown oily substance was obtained.

[0491] .sup.1H-NMR (CDCl.sub.3) δ values: 7.79-7.69 (4H, m), 7.40-7.32 (4H, m), 5.04-4.75 (3H, m), 4.33-4.26 (1H, m), 3.24 (2.13H, s), 3.22 (0.87H, s), 3.19-2.98 (2H, m), 2.75-2.45 (6H, m), 2.31 (0.87H, s), 2.29 (2.13H, s).

Example 19

[0492] ##STR00075##

[0493] 30.2 g of potassium carbonate was added to 463 mL of a methanol solution containing 119 g of S-(((2S,3S,4R)-5-methoxy-3,4-bis((4-methylphenyl)sulfonyloxy)tetrahydrofuran-2-yl)methyl) ethanethioate in a nitrogen atmosphere, followed by stirring for 1 hour at 25° C. and then for 1 hour at 60° C. The reaction mixture was cooled to 15° C., and 170 g of a 50% aqueous sodium hydroxide solution was added dropwise thereto at a temperature of equal to or lower than 25° C. The reaction mixture was stirred for 1 hour at 60° C. and then cooled to 10° C. Insoluble matters were removed by filtration, and the solvent was distilled away under reduced pressure. Toluene was added to the obtained residue, and the solvent was distilled away under reduced pressure, thereby obtaining 35.4 g of (1S,4S,7S)-3-methoxy-2-oxa-5-thiabicyclo[2.2.1]heptan-7-ol as a reddish brown oily substance.

[0494] 213 mL of toluene, 1.82 g of tetrabutylammonium chloride, and 70.4 g of a 50% aqueous sodium hydroxide solution were added to the obtained (1S,4S,7S)-3-methoxy-2-oxa-5-thiabicyclo[2.2.1]heptan-7-ol. The mixture was cooled to 10° C. and stirred, and then 37.1 g of p-toluenesulfonyl chloride was added dropwise thereof in a state where the internal temperature was kept at a temperature of equal to or lower than 15° C. The mixture was heated to 25° C., and water and toluene were added thereto, followed by stirring for 3 hours at 25° C. Toluene and water were added to the reaction mixture. An organic layer was collected by separation, washed with a 25% aqueous sodium chloride solution, treated with 3 g of activated carbon, and then dried over anhydrous magnesium sulfate, and the solvent was distilled away under reduced pressure. As a result 38.6 g of (1S,4S,7S)-3-methoxy-2-oxa-5-thiabicyclo[2.2.1]heptan-7-yl 4-methylbenzoate as an orange oily substance was obtained.

[0495] .sup.1H-NMR (CDCl.sub.3) δ values: 7.94-7.89 (2H, m) 7.27-7.22 (2H, m), 5.58 (0.37H, t), 5.43 (0.63H, t), 5.34 (0.63H, d, J=2.4 Hz), 4.97 (0.37H, s), 4.74-4.71 (0.37H, m), 4.67-4.65 (0.63H, m), 3.81 (0.63H, t, J=2.4 Hz), 3.59 (0.37H, d, J=2.4 Hz), 3.54 (1.89H, s), 3.40 (1.11H, s), 3.09 (1.26H, d, J=1.5 Hz), 3.02-2.91 (0.74H, m), 2.41 (3H, s).

Example 20

[0496] ##STR00076##

[0497] 77 mL of 2 mol/L hydrochloric acid was added to 386 mL of a tetrahydrofuran solution containing 38.6 g of (1S,4S,7S)-3-methoxy-2-oxa-5-thiabicyclo[2.2.1]heptan-7-yl 4-methylbenzoate, followed by stirring for 1 hour at 50° C. The reaction mixture was cooled to 5° C., 15.6 g of sodium hydrogen carbonate was added thereto, and then 104 g of sodium borohydride was added thereto in a state where the internal temperature was kept at a temperature of equal to or lower than 20° C. the reaction mixture was stirred for 10 minutes at a temperature of equal to or lower than 20° C. and then stirred for 1.5 hours at 25° C. The reaction mixture was cooled to 5° C., and 75 mL of 6 mol/L of hydrochloric acid was added dropwise thereto in a state where the internal temperature was kept at a temperature of equal to or lower than 20° C. Ethyl acetate and water were added to the reaction mixture. An organic layer was collected by separation, washed sequentially with a 25% aqueous sodium chloride solution, a mixed solution of a 7.5% aqueous sodium hydrogen carbonate solution and a 25% aqueous sodium chloride solution, and a 25% aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate, and the solvent was distilled away under reduced pressure. 50 mL of ethyl acetate was added to the obtained residue and dissolved by heating, and then 100 mL of hexane was added thereto. Solids were collected by filtration, thereby obtaining 12.2 a (2R,3S,4S)-4-hydroxy-2-(hydroxymethyl)tetrahydrothiophen-3-yl 4-methylbenzoate as a white solid.

[0498] .sup.1H-NMR (CDCl.sub.3) δ values: 7.90 (2H, d, J=7.8 Hz), 7.25 (2H, d, J=7.8 Hz), 5.37 (1H, t, J=2.7 Hz), 4.55-4.47 (1H, m), 4.15-4.06 (1H, m), 4.03-3.97 (1H, m), 3.79-3.73 (1H, m), 3.69-3.66 (1H, m), 3.34-3.28 (1H, m), 3.08-3.02 (1H, m), 2.91 (1H, br), 2.42 (3H, s).

Example 21

[0499] ##STR00077##

[0500] 2.68 g of (2R,3S,4S)-4-hydroxy-2-(hydroxymethyl)tetrahydrothiophen-3-yl 4-methylbenzoate was dissolved in a mixed solution of 15 mL of methanol and 10 mL of tetrahydrofuran, and 58 mg of a 28% sodium methoxide/methanol solution was added thereto, followed by stirring for 4 hours at room temperature. The solvent was distilled away under reduced pressure. Ethyl acetate and water were added to the obtained residue. An aqueous layer was collected by separation and washed with ethyl acetate. An organic layer was extracted using water. The aqueous layer and the extract liquid were mixed together, and water was distilled away under reduced pressure, thereby obtaining 1.48 g of (2R,3S,4S)-2-(hydroxymethyl)tetrahydrothiophene-3,4-diol as a colorless oily substance.

[0501] .sup.1H-NMR (DMSO-D.sub.6) δ values: 5.12 (1H, d, J=4.5 Hz), 5.08 (1H, d, J=4.5 Hz), 4.82 (1H, t), 3.99-3.92 (1H, m), 3.76-3.68 (2H, m), 3.39-3.31 (1H, m), 3.11-3.04 (1H, m), 2.912.84 (1H, m), 2.59-2.52 (1H, m).

Example 22

[0502] ##STR00078##

[0503] 2.4 g of tert-butoxypotassium was added to 50 mL of a tetrahydrofuran solution containing 10 g of 1-phenylethane-1,2-diol and 10.2 g of dimethyl methoxymethylene malonate at 25° C., followed by stirring for 5.5 hours at 25° C. 40 mL of toluene was added to the reaction mixture, tetrahydrofuran was distilled away under reduced pressure, and then ethyl acetate and water were added thereto. An organic layer was collected by separation, washed sequentially with water, 1 mol/L hydrochloric acid, and a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate, and the solvent was distilled away under reduced pressure. The obtained residue was purified by column chromatography, thereby obtaining 6.2 g of dimethyl-2-(4-phenyl-1,3-dioxolan-2-yl)malonate as a colorless oily substance.

[0504] .sup.1H-NMR (CDCl.sub.3) δ values: 7.39-7.33 (5H, m), 5.90 (0.5H, d, J=6.9 Hz), 5.73 (0.5H, d, J=6.9 Hz), 5.11 (1H, m), 4.44-4.25 (1H, m), 3.80-3.78 (6H, m), 3.77-3.72 (2H, m).

Example 23

[0505] ##STR00079##

[0506] 146 mg of diethylamine was added to a solution of 2 mL ethyl acetate and 2 mL of water containing 280 mg of dimethyl 2-(4-phenyl-1,3-dioxolan-2-yl)malonate at 25° C., followed by stirring for 2 hours at 25° C. An organic layer was collected by separation, washed sequentially with water, 1 mol/L hydrochloric acid, and a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate, and the solvent was distilled away under reduced pressure.

[0507] As a result of measuring .sup.1H-NMR of the obtained residue, it was confirmed that 1-phenylethane-1,2-diol was generated, and the reaction rate was 96%.

[0508] (23-2)

[0509] 232 mg of a 28% sodium methoxide/methanol solution was added to 2 mL of a methanol solution containing 280 mg of dimethyl 2-(4-phenyl-1,3-dioxolan-2-yl)malonate at 25° C., followed by stirring for 3 hours at 25° C. Ethyl acetate and water were added to the reaction mixture. An organic layer was collected by separation, washed sequentially with water. 1 mol/L hydrochloric acid, and a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate, and the solvent was distilled away under reduced pressure.

[0510] As a result of measuring .sup.1H-NMR of the obtained residue, it was confirmed that 1-phenylethane-1,2-diol was generated, and the reaction rate was 100%.

[0511] (23-3)

[0512] 166 mg of potassium carbonate was added to 2 mL of a methanol solution containing 280 mg of dimethyl 2-(4-phenyl-1,3-dioxolan-2-yl)malonate at 25° C., followed by stirring for 3 hours at 25° C. Ethyl acetate and water were added to the reaction mixture. An organic layer was collected by separation washed sequentially with water, 1 mol/L hydrochloric acid, and a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate, and the solvent was distilled away under reduced pressure.

[0513] As a result of measuring .sup.1H-NMR of the obtained residue, it was confirmed that 1-phenylethane-1,2-diol was generated and the reaction rate was 93%.

[0514] (23-4)

[0515] 100 mg of a sodium hydrogen carbonate was added to 2 mL of a methanol solution containing 280 mg of dimethyl 2-(4-phenyl-1,3-dioxolan-2-yl)malonate at 25° C., followed by stirring tor 3 hours at 25° C. Ethyl acetate and water were added to the reaction mixture. An organic layer was collected by separation, washed sequentially with water, 1 mol/L hydrochloric acid, and a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate, and the solvent was distilled away under reduced pressure.

[0516] As a result of measuring .sup.1H-NMR of the obtained residue, it was confirmed that 1-phenylethane-1,2-diol was generated, and the reaction rate was 92%.

[0517] The compound of the present invention is useful as an intermediate for manufacturing salacinol useful as a bioactive substance, and the manufacturing method of the present invention is useful as a method for manufacturing salacinol.