JPH01180892A - Production of l-glucose by epimerization of l-mannose catalyzed by molybdate in presence of epimerization inhibitor - Google Patents

Abstract

PURPOSE: To obtain the compounds such as artificial sweetemer with a high yield by allowing to react aqueous mixture containing specific amounts of L-mannose, epimerization-inhibitors and HCN-addition inhibitors of L-arabinose by a molybdate catalyst under specified conditions.

CONSTITUTION: An aqueous mixture containing at least 40% of L-mannose in dry solid base, epimerization-inhibitor catalyzed by molybdate, and inhibitors produced by adding hydrogen cyanide to L-arabinose is allowed to react by a molybdate catalyst of an amount corresponding to 200-2500 ppm molybdenum for epimerization under the conditions of pH 3 or less and at a temperature suitable for epimerization for a period until the ratio of L-glucose: L-mannose becomes at least 1 to obtain L-glucose from L-mannose at a high yield. In addition, it is preferable that the temperature for epimerization is within a range of 75-100°C.

COPYRIGHT: (C)1989,JPO

Description

DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to a process for producing L-glucose by molybdate-catalyzed epimerization of L-mannose, and in particular to the production of L-glucose by this route. The present invention relates to a method for producing glucose in the presence of epimerization inhibitors that have hitherto hindered production. The present invention is based on pH
This includes carefully adjusting the value below 30 and carefully controlling the epimerization temperature.

[Background of the Invention] Recent dietary demands and ancestral preferences have led to the development of natural sugar substitutes, including sucrose and fructose.
Increased consumption of artificial sweeteners. And although conventional artificial sweeteners are not perfect as their physiological effects are still being observed over a long period of time, the demand for them remains unabated. With the increasing demand for artificial sweeteners in the commercial sector with economic shocks, the discovery and supply of new artificial sweeteners is once again gaining importance.

The ideal artificial sweetener would be low in calories, non-causing, have no deleterious physiological effects, and be usable by diabetics. If the sweetener is not metabolized by humans and is not metabolized by M (Nora) in the mouth and intestinal tract, and if the sweetener is not absorbed by humans or does not affect the internal organs even if absorbed, then the above-mentioned The requirements will be met. That is, an ideal sweetener should be excreted in the same form as it is ingested. Another desirable feature is that it has similar bulk properties to sucrose so that it can be substituted for granulated sugar in many formulations.

Recently, there has been increasing interest in L-sugars as desirable artificial sweeteners. It has been known since at least 1946 that L-fructose has a sweet taste (1-
1,1, Wolfrom and A, Thompson
, J. AmChem, Soc, ,68,791,7
93 (1946)), and it has also been known since at least 1890 that L-Fix is non-fermentable and is not metabolized by microorganisms that normally metabolize slime ([, F i 5her, Ber, Deu-
tsch, CI] em, Ges,, 23,370,3
89 (1890)), although not necessarily accurate, L-
It is also reasonable to assume that fructose is not metabolized by humans. Given that L-fructose is a sweet non-metabolite, it is clear that it can be used as a low-calorie sweet 1N in many formulations. Recently, Schallenberger (Sl+a)
Lenberger and his co-workers have shown that many L-sugars are present in their D-enantiomers.
hs) was proven to have a sweetness comparable to that of Nat
Llre, 221,555 (4969), G, G, B
1.Beider (Springer
Velag, 1971), ed., "The Dovebook on Sensory Physiology", Vol. 4, pp. 241-5.

The relative availability of L-sugar has prevented its utilization. For example, fructose is not found in sufficient quantities in nature. This lack of availability has led to significant efforts to develop commercially viable processes for producing L-sugars as commercial products in quantities that meet demand. U.S. Patent Nos. 4,371,616 and 4,42
No. 1,568 describes a method for making a readily available glutinous paste containing monoglucose, monoidose, and L-glucose. U.S. Pat. No. 4,262,032 describes the preparation of a number of thickeners, the focus of which is on typical experimental methods that are not suitable for economical industrial production. US Pat. No. 4,440,855 shows a flow scheme for preparing a mixture of L-glucose and L-mannose. and U.S. Patent No. 4.20
The subject of No. 7,413 is monosucrose, the common enantiomer of granulated sugar, which upon hydrolysis yields L-fructose and L-glucose.

When determining L-glucose, L-glucose is usually
- Found as a mixture with mannose. A method for obtaining a mixture of L-mannose and glucose is described in US Pat. No. 4,584,447. Separation of L-glucose from L-mannose can be carried out by various methods, but the presence of mannose in the raw material to be separated increases the cost of purified L-glucose, and the mannose content in the raw material is high. The more it is, the higher the cost will be.

Unfortunately, mixtures of L-glucose and L-mannose have a kinetic control advantageous to L-mannose that results in very high losses in producing relatively pure L-glucose. Usually manufactured under Because glucose is thermodynamically favored compared to mannose (Hayes et al.

Amer, Chem, SOC,,104,6764
(1982)), substantial cost savings can be achieved if the raw material to be separated is an equilibrium mixture of L-glucose and L-mannose.

Equilibrium mixtures for separation can be obtained by preparing a glucose-mannose mixture under equilibrium control, or alternatively by equilibrating the product mixture under kinetic control. For various reasons, the latter is the more promising route, and it is this that led to the balancing means of the present invention. Given the proposed uses for L-glucose, it is imperative to minimize n1 organisms and color body formation and to minimize cost.

The requirement to epimerize t'1-mannose to L-glucose in a mixture containing both L-mannose and L-glucose directed the inventors' attention to soluble molybdates as an equilibration tool. . In Czechoslovakia inventor's certificate 149,463, Bilik
ik) demonstrated that molybdic acid epimerizes an aqueous solution of L-mannose, giving a mixture in which the ratio of L-glucose:L-mannose is probably 3:1. Ha Ves et al. (see the above-mentioned book) sought to elucidate the mechanism of this epimerization to some extent). In fact, molybdate readily epimerizes pure mannose. Under similar conditions molybdate is the reaction product L-
It is surprising that a mixture of mannose and L-glucose cannot be epimerized. Further research into this unexpected phenomenon revealed its cause and found a way to avoid this inconvenience.

[Summary of the Invention] The object of the present invention is to process L-mannose and L-mannose produced when cyanohydrin is prepared by adding hydrogen cyanide to pentose.
- To provide a method for increasing the yield of L-glucose from a mixture of glucose, in particular when the mixture contains an inhibitor of molybdate-catalyzed epimerization; It relates to a method for increasing the yield when followed by hydrogenation with hydrolysis of cyanohydrin. One characteristic is that epimerization is lower than 3
It is carried out by IH, preferably about 13 to about 27 p.
This is what H does. and in particularly preferred embodiments, about 13 to about 27 1111 at a temperature of about 80°C to 100°C.
Epimerization takes place.

[Description of the Invention) E] The present invention contains a small amount of a substance that inhibits the epimerization of L-mannose catalyzed by a molybdenum M salt, and further contains a mixture containing L-mannose and L-glucose. This is a method that produces high yields. In particular, L-
The mannose-containing aqueous solution is a mixture resulting from the hydrogen cyanation addition of L-arabinose. Hydrocyanation of this pentose gives a mixture of cyanohydrin and imine as a hydrogenation intermediate, the cyanohydrin is converted to hexose by hydrogenation with hydrolysis, and the imine is finally converted to monomannose and L- becomes a mixture of glucose.

This entire series of reactions is hereinafter referred to as hydrogen cyanide addition-hydrogenation-hydrolysis.

L-hexoses can generally be obtained by carbon chain extension of L-glucose, usually arabinose. L-
The synthetic means for preparing glucose is
- produces a mixture of both mannose. This mixture generally has kinetic co-dominance of the product.
mannose is the predominant epimer, reflecting the An example of a method incorporating the features described above is described in US Pat. No. 1t, 584,447. Equilibration of a pair of glucose and mannose epimers results in a glucose to mannose ratio of approximately 2°1, which is extremely favorable for reducing the production cost of L-glucose.

Epimerization of an aqueous solution of pure monomannose with molybdate at a concentration of 600 ppm is carried out at 80°C, pH
It progressed easily with 4 and 5 and reached equilibrium in about 35 hours, and 6
Provide a Hei 111i mixture containing slightly more than 0% glucose. However, if the solution is a reaction product resulting from the hydrogen cyanation addition of L-arabinose, inter alia
If the solution contains mannose and glucose, the solution is treated with molybdate under the same conditions and no measurable epimerization occurs even after 22 hours. In fact, epimer equilibration within 5 hours is not achieved until the molybdate concentration reaches 1 l 1000 pp. Even with an equilibration time of 22 hours, the required molybdate concentration is 5oooppm. Subsequent research revealed that
The above situation occurs when the raw material undergoes hydrogen cyanide addition.
It is a reaction product when L-glucose is prepared from arabinose, and it has been revealed that it is produced due to the presence of inhibitors in it. Surunawa, hydrogen cyanide addition-
The formation of L-glucose in the hydrogenation-hydrolysis reaction sequence is accompanied by other components that act as inhibitors in the molybdate-catalyzed epimerization of mannose to glucose. Since L-arabinose is the most reasonable starting point to the L-glucose system, these inhibitors are certain to exist regardless of the particular preparative route taken for L-glucose production.

This fact required the inventor to eliminate the above-mentioned inhibitory effect, and the inventor's subsequent research was directed towards solving this problem. Although the precise nature of the inhibitors is unknown and their relative importance unknown, gluconamide
ide > and cyanide are both thought to be present, and both were found to exert an inhibitory effect.

The present invention's approach to overcoming the above-mentioned inhibitory effects is aided by two key findings. One of the findings is that the inhibitory effect decreases with decreasing pH. Another finding, which is perhaps more important, is that the inhibitory effect is greatly improved at higher temperatures. Based on these findings, at low concentrations of molybdate, i.e. ca.
Epimerization could be carried out at the desired Molybuty 21m concentration of less than 500 D p m and within only a few hours.

The raw material of the present invention is a reaction product obtained by the addition of hydrogen cyanide to arabinose. Since the cyanohydrin obtained by hydrogen cyanide addition is most easily converted to the corresponding hexose via the hydrogenation-hydrolysis sequence, the reaction product obtained starting from cyano-arabinose in the hydrogen cyanation-hydrogenation-hydrolysis sequence. are the preferred raw materials of the present invention. However, harmful inhibitors of molybdate-catalyzed epimerization are largely generated during the hydrocyanation process, so that L-
The present invention also includes raw materials obtained by adding hydrogen cyanide to arabinose. Furthermore, the material obtained by separating a mixture of L-glucose and L-mannose is also a raw material of the present invention, and the mixture is obtained by the addition of hydrogen cyanide to arabinose, and the separation can be performed by chromatographic separation or crystallization. This can be done by any suitable means.

The feedstock can contain up to about 50% dry solids. Preferably, the raw material is as concentrated as possible to minimize the total volume of solution that must be processed. Typical reaction products contain from about 40 to about 80% mannose, with up to about 99% of the dry solids being mannose. However, the epimerization process described herein can be performed regardless of the percentage of mannose.

The arabinose content of the feedstock is from a low of 0.5% of the dry solids present to a high of about 12% of the dry solids present.

However, it typically ranges from about 2% to about 10% by weight of total dry solids.

Under epimerization conditions, the epimerization feedstock contains at least about 20
Molybdate salts which are soluble at concentrations of 0.000 ppm are used in the present invention. An example of a water-soluble molybdate that can be used in the practice of this invention is sodium molybdate, Na Mo
C2 and potassium molybdate K MOO4. Although molybdenum trioxide is not generally considered a soluble molybdate, it can also be used in the present invention since it dissolves in the epimerization feedstock at a concentration of about 2000 ppm under epimerization conditions. Other suitable molybdates that can be used in the present invention include iron molybdate, calcium molybdate, ammonium molybdate, molybdenum dioxide, and molybdenum (Vl) oxide bis(2,4-pentanedionate). included.

The concentration of soluble molybdate for epimerization is
Concentrations that give about 2000 ppm or less of molybdenum are sufficient, with about 200 D I) m and about 1500 p o
Concentrations between m are preferred. Although there are no disadvantages to using molybdates that provide molybdenum in excess of 2500 ppm, there is no substantial benefit. In order to eliminate the inhibitory effect of catalyst poisons present in the raw materials, it is important to carry out epimerization at a pH of 30 or less. This is surprising in view of U.S. Pat. No. 4,029,878, which warns against performing epimerizations at l]■ below 3. The lower limit of 1]11 for performing epimerization depends somewhat on the epimerization temperature, which is usually in the range of 75 to 100°C. Preferably, epimerization is carried out at a pH of about 1.3 to about 27, and the lower the temperature, the lower the IIH. For practical considerations, epimerization conditions are chosen so that the reaction time does not exceed about 20 hours, preferably about 10 hours. This time limit is a limitation derived from minimizing the amount of by-products associated with epimerization, such as substances that color the epimerization mixture. In practice, it is desirable to complete epimerization in a period slightly less than that required to reach equilibrium. for example,
Ninety percent of the equilibrium L-glucose level can be obtained in about 172 seconds of the time required to reach equilibrium, and the reduction in reaction time far outweighs the reduction in conversion of L-glucose. Practically, it is most economical to carry out epimerization for a time such that the ratio of L-glucose to L-mannose is at least 1.1.

The method of the invention can be described as follows. L-
The feedstock obtained by hydrocyanation of arabinose and containing at least 40% L-mannose on a dry solids basis is epimerized in the presence of soluble molybdate in an epimerization reactor.

Soluble molybdate can be present in concentrations providing up to about 2500 ppm molybdate, but most preferably when about 200 to 1500 ppm molybdate is present. Epimerization generally ranges from about 75 to about 1
00°C, more preferably 80-95°C, about 30°C.
The process is carried out at the following pH 1, usually from about 13 to about 27, until epimerization to a desired degree of culm is achieved. Prior to separating the hexose from the epimerized feed, it is desirable to remove the molybdenum M salt, most preferably by contacting the epimerized feed with a substance that removes molybdate by ion exchange, usually an ion exchange resin. Remove. Strong base anion exchange resins of the slylene-divinylbenzene type are suitable. If it is desired to minimize the amount of all ions, the feedstock can also be treated with both anion and cation exchange resins prior to chromatographic separation. In one embodiment, after epimerization is complete, the epimerized mixture is sent to an ion exchange column to remove molybdate. The molybdate-free mixture is then used as feed for a chromatographic separator, which separates the L-glucose rich stream and the L-
Produces a glucose-poor stream. U.S. Patent No. 4,4
No. 71,144 and British Patent No. 1.540.556 describe such separations. The L-glucose poor stream is L-arabinose rich and this stream can be mixed with the feed to the epimerization reactor and recycled to the reactor. The stream rich in L-glucose is separated and recovered.

In other applications, it is desirable to epimerize feedstocks that are substantially low in glucose. For example, if the reaction product contains primarily L-glucose, it is not cost effective to equilibrate the mixture before separating L-glucose from L-mannose. In such cases, after separation of the L-glucose, the stream containing L-mannose is separately epimerized with molybdate with 0.5 to about 12% di-arabinose, and after separation of the molybdate, the remainder is separated. Supply to the device. Other embodiments of the invention are possible and will be understood by those skilled in the art.

The specific examples shown below are for illustrating the present invention and are not intended to limit the present invention.

Example Epimerization of L-mannose: Obtained by hydrogen cyanide addition of L-arabinose, containing 9.7 wt% L-mannose.
An aqueous solution containing o, swt% of di-arabinose and 0.2 wt% of di-glucose was used as a raw material for epimerization. Add 0.78j;l of sodium molybdate to 500g of this solution and add 600 p 1+ m of N4
A solution containing 0 was obtained. The pH was adjusted to 50 by adding sulfuric acid and the solution was heated to 80°C. After 7 hours epimerization was virtually complete. 73! 1 of sodium molybdate was added incrementally to bring the total MOfi in the solution to 640011.
tl nl. Adjust the pH of this solution to 50,
It was heated again to 80°C. The experimental results are shown below.

(Left below) Table 1: Epimerization of L-mannose at 80°C in raw materials containing L-arabinose MO time Composition of product (%) (Dp
m) (hr) Glucose Arabinose Mannose 1300 0 1.3
7,0 91.7+, o 13
6.7 91.82.5
2.2 6.9 9103.75
2.3 7. +90.
66.0 2.5 G, 8
90.77.0 2.3 6,9
90.86400 0 2.5
G, 7 89. +1.0 1
1.8 7,0 81.2275
252 6.6 6824.5
33.1 6.4 5G,
77.0 44.3 6,4
45,222.0 65.2 5,
Using pure [)-vn/-') containing 6001111 m of 626.3M O as the raw material (
In a comparative experiment conducted with 184,5, epimerization occurred easily and glucose °mannose-50:
A 60:40 mixture was obtained in about 4 hours. In contrast, the table above shows that the epimerization of mannose in the feedstock is 80
Even after 7 hours at
Even with 400 p p +n of Mo, a 50:50 mixture is obtained after 7 hours (3 times longer reaction time).

Example 2 l) Effect of H to eliminate the influence of catalyst poison ゛ Obtained by hydrogen cyanide addition of L-arabinose, +2.6 wt% L-
Mannose and 0.07wt% L-glucose and 0.5
An amount of sodium molybdate to obtain the desired Mo 1 degree was converted to an aqueous feedstock containing wt% L-arabinose. 10% sulfuric acid was added to the solution to adjust the desired PL, and epimerization was performed. By plotting the relationship between glucose yield and epimerization time, a mixture of glucose and mannose (60:40) can be obtained (yield: 60:40).
%) time was determined. The time, MO concentration and pH as a function of temperature are summarized in Table-2.

Table 2 Effects of rll-1, molybdenum concentration, and temperature on epimerization time to obtain a yield of 6o% Temperature (°C) pl (vosi (ppm) Bi
E] (hr)80 L8 2000
4.51250 9, 0 500 17.0 2.3 2500 4.01500
1+, 0 750 23, 0 3.0 2500 13.0150
0 35.0 95 2.3 1250 1
75500 7.0 3.0 2500 1.51500
3.9 750 g, 5 The above data shows a reasonable amount of molybdenum (not more than 1500111r1m) if the reaction time is limited to 10 hours.
shows that the epimerization at 80° C. must be carried out at a pH of about 23 or less, and at 95° C. the l)H must be 30 or less.

Example 3 Identification of catalyst poison In order to investigate the inhibitory effect (poisonous effect) of a known substance or a substance thought to appear in the epimerization raw material, a different substance was added to a pure mannose solution before epimerization. Molybdate was used at a concentration giving 50011 p nl of molybdenum, epimerization was carried out at pH 2,
3. Conducted at a temperature of 95°C. This temperature and pH has been found to be extremely effective in eliminating the inhibitory effects of catalyst poisons in the reaction product obtained by adding cyanide to arabinose. Therefore, the inhibitory effect demonstrated in this example indicates the strength or extent of the light pollution exerted by the added substance.

FIG. 1 shows the inhibitory effect of gluconamide 1~, and FIG. 2 shows the inhibitory effect of cyanide. These inhibit epimerization even at relatively low concentrations.

[Brief explanation of the drawing]

FIGS. 1 and 2 are graphs showing the epimerization disturbance caused by the two species commonly present in the product mixture obtained from the hydrogen cyanation-hydrogenation-hydrolysis of L-arabinose.

Claims (1)

[Scope of Claims] 1. Contains at least about 40% L-mannose on a dry solids basis and further contains a substance that inhibits the epimerization reaction catalyzed by molybdate, which occurs in the hydrogen cyanide addition of L-arabinose. From an aqueous mixture containing inhibitors, the epimerization of L-mannose to L-glucose is catalyzed by a solution of molybdate.
In a method for improving the yield of glucose, the epimerization is carried out using a molybdate catalyst in an amount corresponding to 200 to 2500 ppm of molybdenum, at a pH of 3.0 or less, and at an epimerization temperature of L. -Glucose versus L-
A method for improving the yield of L-glucose, characterized by carrying out an epimerization reaction for a time until the ratio of mannose becomes at least 1. 2. The method of claim 1, wherein the epimerization reaction is catalyzed with soluble molybdate at a concentration giving a molybdenum content of 200 to 1500 ppm. 3. The method according to claim 1, wherein the epimerization temperature is between 75 and 100°C. 4. The method of claim 1, wherein soluble molybdate is removed from the reaction product stream with an ion exchange resin. 5. The method of claim 1, wherein the pH of epimerization is between about 1.3 and about 2.7. 6. The method according to claim 1, wherein the epimerization temperature is between 80 and 95°C.