Production of D-sorbitol by hydrogenation

Abstract

The present invention relates to a novel and inventive process for the production of sorbitol from D-sucrose.

Claims

1. A process for producing D-sorbitol from sucrose, wherein the process comprises the steps of: (a) converting the sucrose to oxidized products substrate using glucose-fructose oxidoreductase (GFOR) enzyme; and thereafter (b) hydrogenating the oxidized products substrate in a hydrogenation step at a pressure of about 10 bar to about 60 bar and a temperature from about 30 C. to about 100 C. in the presence of a H.sub.2 gas and a transition metal-based complex selected from the group consisting of transition metal based complexes according to formulas (III) to (VIII): ##STR00002##

2. The process according to claim 1, wherein the process is carried out in the presence of a solvent selected from the group consisting of non-aqueous solvents, organic solvents and polar solvents.

3. The process according to claim 1, wherein a molar ratio of the substrate to the transition metal based complex is in the range of about 50 to about 100000.

4. The process according to claim 1, wherein the process is carried out in the presence of at least one base.

5. The process according to claim 4, wherein the at least one base comprises at least one alkoxide base.

6. The process according to claim 2, wherein the solvent is selected from the group consisting of alcohols, ethers and amides.

7. The process according to claim 2, wherein the solvent is selected from the group consisting of methanol, ethanol, propanol and tetrahydrofuran (THF).

8. The process according to claim 3, wherein the molar ratio of the substrate to the transition metal based complex is about 5000 to about 30000.

Description

EXAMPLE 1: HYDROGENATION OF GLUCONOLACTONE-SORBITOL MIXTURES

(1) General Procedure for Hydrogenation: Samples of gluconolactone and sorbitol samples in various ratios (1.0 mmol total substrate amount) were weighed into 5-mL crimp vials and transferred in N.sub.2-filled glovebox. All further manipulations were done in the N.sub.2-filled glovebox. Into these samples, KOMe solution in methanol (5 mol % wt total substrate) and catalyst solution/slurry in methanol (0.5 mol % wt total substrate, S/C 200) were added; volume was further diluted to 3.0 mL with methanol. These vials were capped with PTFE coated septum and placed inside a Premex 96er parallel hydrogenation reactor. The system was purged with N.sub.2 (310 bar) and H.sub.2 (310 bar). The reactions were carried out at 50 bar H.sub.2, 70 C. for 16 h with stirring (300 rpm). After the reaction, HPLC samples were prepared in deionized H.sub.2O. Concentrations of the gluconolactone and sorbitol in the reaction were determined using calibration curves.

(2) Analysis: Products were analyzed with HPLC using Agilent Technologies 1260 Infinity instrument equipped with Waters 2414 Refractive Index Detector. The parameters are column: BIORAD Aminez-HPX-87H, 3007.8 mm, column temperature: 50 C., flow rate: 0.55 mL/min, injection volume: 100 L, eluent: 5 mM H.sub.2SO.sub.4(aq), collection time: 60 min. Retention times, min: gluconolactone=9.6, sorbitol=10.9.

(3) TABLE-US-00001 TABLE 1 Gluconolactone (Glul)-to-sorbitol (Sor) ratio using the transition metal- based complex of formula (III) as catalyst (Conditions: 1 mmol total amount of gluconolactone and sorbitol at varying ratios, 5 mol % KOMe, 0.5 mol % of complex according to formula (III), 3 mL total volume methanol, 50 bar H.sub.2, 70 C., 16 h, HPLC analysis in H.sub.2O, DF = 168). Glucl:Sor Glucl Sor Conversion ratio [mM] [mM] [%] 1:9 5.3 391 87 3:7 5.6 388 95 7:3 9.2 477 97 9:1 10.2 401 97 10:0 8.9 379 98

EXAMPLE 2: PRODUCTION OF SORBITOL FROM SUCROSE UNDER STANDARD CONDITIONS

(4) A modified strain of Zymomonas mobilis ATCC 29191 devoid of gluconolactonases activity is obtained by knockout of the known genes for this activity [Kanagasundaram V, Scopes R. 1992 Biochim Biophys Acta, 1171(2), 198-200].

(5) Biomass of gluconolactonase-deficient Zymomonas mobilis ATCC 29191 is produced by cultivation on 100 g/l glucose, 5 g/l yeast extract, 0.5 g/l of potassium dihydrogen phosphate, 0.5 g/l of magnesium sulfate (7H.sub.2O), 20 mg/l of ammonium ferrous sulfate (6H.sub.2O), 1 mg/l of biotin, and 2 mg/l of calcium pantothenate at pH 7.0 and 28 C. After cultivation, the culture broth is centrifuged to harvest the biomass and washed with isotonic saline (8.5 g/l).

(6) The biomass is treated with toluene (10% v/v in pH 7 buffer) in order to increase the permeability.

(7) A 3 ml aqueous solution is prepared, containing 0.5 g (wet weight) toluene-treated biomass together with 0.81 g glucose and 0.81 g fructose, corresponding to a concentration of 1.5 M for each sugar. The reaction temperature is maintained at 39 C. and the pH at 6.2 by the addition of 2M Na.sub.2CO.sub.3. Over 420 min, 96% of the substrate are converted, with essentially equivalent amounts of both gluconolactone and sorbitol produced.

(8) The biomass is separated from the reaction mixture by centrifugation. Then, 0.33 ml of the supernatant are lyophilized to remove water and the dried material is dissolved in 3 ml methanol and used as starting material/substrate (=gluconolactone and sorbitol equimolar mix) for the following hydrogenation step.

(9) Exemplified is a hydrogenation using a transition metal-based complex according to formula (III) as catalyst (Conditions: 1 mmol total amount of starting material, 5 mol % KOMe, 0.5 mol % of complex according to formula (III), 3 mL total volume methanol, 50 bar H.sub.2, 70 C., for 16 h, HPLC analysis in H.sub.2O, DF=168), resulting in a conversion yield of gluconolactone to sorbitol of more than 95% or a conversion yield of sucrose to sorbitol in the range of 92%.

EXAMPLE 3: HYDROGENATION USING DIFFERENT TRANSITION METAL-BASED COMPLEXES

(10) To test the influence of different transition-metal based complexes used in the hydrogenation step, the starting material/substrate for the different reactions obtained according to Example 2, with removal of water and dissolving methanol (see above), is used with all transition metal-based complexes according to formula (IV) to (VIII) as described herein for the catalytic reaction. The best results are obtained with a complex according to formula (III) and (V), with a yield of sorbitol from sucrose in the range of at least 91%.

EXAMPLE 4: HYDROGENATION USING DIFFERENT SOLVENTS

(11) To test the influence of the solvent used in the hydrogenation step, production of the starting material is obtained as described (Example 2) with the proviso that the dried material is dissolved in different solvents. The reaction (standard conditions, i.e. use of transition metal-based complex (III), with conditions described in Example 2) works best with alcoholic solvents, including methanol, ethanol or isopropanol, with conversion rates in the range of from 82% (isobutanol) to 96% (ethanol) to 98% (methanol) with regards to conversion of the starting material to sorbitol.

EXAMPLE 5: HYDROGENATION USING DIFFERENT SUBSTRATE TO CATALYST RATIOS

(12) To test the influence of the S/C ratio used in the hydrogenation step, production of the starting material is obtained as described (Example 2) with the proviso that different amounts of substrate is used for the reaction (standard conditions, i.e. use of transition metal-based complex (III), with conditions described in Example 2). An S/C in the range of 5000 to 20000 works with more or less 100% conversion rates, a decrease by around 30% is seen with an S/C in the range of 50000.

EXAMPLE 6: HYDROGENATION USING DIFFERENT RANGE OF TEMPERATURE AND AMOUNT OF BASE

(13) To test the influence of the temperature and amount of base used in the hydrogenation step, production of the starting material is obtained as described in Example 2 (standard conditions) with removal of water, dissolving in methanol and use of transition metal-based complex (III). In addition to the standard conditions with the use of 5 mol % KOMe, 70 C. (see above), a different set-up contains 1 mol % KOMe, 90 C. No difference in yield is detected, thus still very good yield as described in Example 1 or 2.