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1 8/13/2016 Patent & Utility Model Number Search(Detail) J-PlatPat Help desk (9:00 21:00) Japanese To p p a g e Help list Site map JPO (+81) helpdesk@j platpat.inpit.go.jp Patent & Utility Model Top page Patent& Utility Model Design Trademark Trial & Appeal Patent& Utility Model Number Search Patent & Utility Model Number Search Back Search Help List You can retrieve a variety of patent and utility model gazettes by their numbers. Selected Gazette Previous Document 1/1 Next Document JP, ,A Detail Image CLAIMS DETAILED DESCRIPTION DRAWINGS * NOTICES * JPO and INPIT are not responsible for any damages caused by the use of this translation. 1.This document has been translated by computer. So the translation may not reflect the original precisely. 2.**** shows the word which can not be translated. 3.In the drawings, any words are not translated. DETAILED DESCRIPTION [Detailed Description of the Invention] [Field of the Invention] [0001] The present invention relates to the manufacturing method of the sugar sphingosine from a ceramide saccharide, the manufacturing method of the SUFINGO base from sugar sphingosine, and the manufacturing method of the SUFINGO base from a ceramide saccharide. [Background of the Invention] [0002] A SUFINGO base is a compound with the basic skeleton of the sphingosines which are the lipid which exists in all the organisms. However, naturally, it exists only in a minute amount generally. Therefore, although research of the physiology activity was delaying, interesting physiology activity, such as toxicity over intestinal tumorigenesis, an inflammatory reaction, and colon cancer, has been reported in recent years. [0003] On the other hand, glycoside ceramide is the main ingredients which exist in an organism widely universally and reach also to 20% in the lipid in a cell membrane. If the conversion to a SUFINGO base from a glueosylceramide is attained, a various kinds of SUFINGO base can be supplied inexpensive. As a converting method from a glueosylceramide to a SUFINGO base, the drawing１ hydrolysis method by chloride or barium hydroxide is known (nonpatent literatures 1 3). [Citation list] [Nonpatent literature] [0004] [Nonpatent literature 1] Lipids 39, , [Nonpatent literature 2] Plant Physiol. 95, 58 68, 1991 [Nonpatent literature 3] J.Biological.Chem. 281, , 2006 [Summary of Invention] [Problem to be solved by the invention] [0005] However, in order that a various kinds of by product may generate in the chloride of the description to the nonpatent literatures 1 3, or the hydrolysis method of the glueosylceramide by barium hydroxide, there are problems, like the yield of the SUFINGO base made into the object is very low, and it is not practical. [0006] Then, the present invention is offer of the new manufacturing method of a SUFINGO base which uses ceramide saccharides, such as a glueosylceramide, as a raw material. The purpose is to provide a method that a SUFINGO base which is an objective product can be selectively manufactured with high yield. [0007] Furthermore, the present invention hydrolyzes ceramide saccharides, such as a glueosylceramide, hydrolyzes offer of the method that sugar sphingosine can be selectively manufactured with high yield, and sugar sphingosine, and offers the object the method that a SUFINGO base can be selectively manufactured with high yield. 1/11

2 [Means for solving problem] [0008] When converting ceramide saccharides, such as a glueosylceramide, to a SUFINGO base, there is two combination cut. One is an amide bond and another is a glycosidic linkage of sugar (for example, glucose) and a side chain. A glycosidic linkage is a generally firm combination and needs strong, acid conditions for the cutting. Although how to use a sugar hydrolysis enzyme (for example, glycosidase) could be considered as a cutting process of the glycosidic linkage in mild conditions, since it was the strong lipophilicity when it is a glueosylceramide, it could not become a substrate of glycosidase. [0009] Then, in order to thin the strong lipophilicity with the present invention, a chemical reaction removes the fatty acid which is carrying out the amide bond to ceramide saccharides, such as a glueosylceramide, and it ranks second to them, A sugar hydrolysis enzyme like glucosidase was made to act on the sugar sphingosine which arose, and it found out that a SUFINGO base was selectively obtained with high yield by cutting a glycosidic linkage on mild conditions. It found out that hydrolysis of amide was possible for cutting of the amide bond with alternative and high yield, and made it complete the present invention by using alkali metal hydroxide. [0010] The present invention is as follows. [1] It is a manufacturing method of sugar sphingosine including hydrolyzing a ceramide saccharide and obtaining sugar sphingosine, The aforementioned method including that the aforementioned hydrolysis heats a ceramide saccharide at the temperature of 100 degrees C or more under existence of the alcohol system organic compound of 100 degrees C or more of boiling points and an alkali metal hydroxide aqueous solution, and obtains sugar sphingosine. [2] A manufacturing method of the description to [1] whose aforementioned alcohol system organic compound is the aliphatic alcohol compound or alicyclic alcohol compound of the carbon numbers [3] A manufacturing method of the description to [1] which is at least 1 type as which the aforementioned alkali metal hydroxide is chosen from the group which comprises LiOH, NaOH, and KOH, or [2]. [4] A manufacturing method described in any of [1] [3] whose alkali metal hydroxide concentration of the aforementioned alkali metal hydroxide aqueous solution is more than 1M. [5] A manufacturing method described in any of [1] [4] with which the aforementioned hydrolysis is performed under microwave irradiation. [6] A manufacturing method described in any of [1] [5] whose sugar residue of the aforementioned ceramide saccharide and the aforementioned sugar sphingosine is a monosaccharide residue or an oligosaccharide residue. [7] A manufacturing method of the description to [6] whose aforementioned monosaccharide residue is a glucosyl group or a galactosyl group. [8] A manufacturing method described in any of [1] [5] whose aforementioned ceramide saccharide is a glueosylceramide, galactosylceramide, or its mixture. [9] A manufacturing method of the description to [8] whose an aforementioned glueosylceramide, galactosylceramide, or its mixture is a plant source or animal origin. [10] A manufacturing method of the description to [9] whose aforementioned plant is cereals, legumes, or corms. [11] A manufacturing method of the description to [9] whose aforementioned animal origin glueosylceramide is a brain origin glueosylceramide. [12] It is a manufacturing method of a SUFINGO base including hydrolyzing sugar sphingosine and obtaining a SUFINGO base, The aforementioned method including that the aforementioned hydrolysis makes a sugar hydrolysis enzyme act on sugar sphingosine, and obtains a SUFINGO base. [13] A manufacturing method of the description to [12] by which the aforementioned sugar sphingosine is manufactured by the method described in any of [1] [11]. [14] A manufacturing method of the description to [12] in which the aforementioned sugar hydrolysis enzyme contains ** glucosidase at least, or [13]. [15] A manufacturing method of the description to [14] which is ** glucosidase of almond origin of the aforementioned ** glucosidase. [16] 2/11

3 A manufacturing method described in any of [12] [15] with which the aforementioned sugar hydrolysis enzyme further contains ** galactosidase. [17] A manufacturing method described in any of [12] [16] which further includes that the SUFINGO base obtained by the aforementioned hydrolysis is refined using the carrier which has a functional group which has the compatibility over the 2 amino 1,3 diol which a SUFINGO base has. [18] A manufacturing method of the description to [17] whose aforementioned functional group is glutaraldehyde. [Effect of the Invention] [0011] According to the present invention, ceramide saccharides, such as a glueosylceramide, are hydrolyzed, To the method that sugar sphingosine can be selectively manufactured with high yield, the method of hydrolyzing sugar sphingosine and manufacturing a SUFINGO base with high yield selectively, and a pan, The method that the SUFINGO base which is an objective product can be selectively manufactured with high yield by using ceramide saccharides, such as a glueosylceramide, as a raw material can be provided. [Brief Description of the Drawings] [0012] [Drawing 1]The yield of the SUFINGO base obtained by chemical (KOH) hydrolysis and enzymatic hydrolysis of the ceramide saccharide of the various origins is shown. [Drawing 2]The IR spectrum of the compound 40m (upper stage) and the compound 40 (lower stage) is shown. [Drawing 3]The IR spectrum of the compound 41 before and behind an elimination reaction is shown. [Drawing 4]The IR spectrum of the compound 41 before and behind a sphingosine prehension reaction is shown. [Description of Embodiments] [0013] [A manufacturing method of sugar sphingosine] The first modes of the present invention is a manufacturing method of sugar sphingosine including hydrolyzing a ceramide saccharide and obtaining sugar sphingosine. In this method, the aforementioned hydrolysis includes heating a ceramide saccharide at the temperature of 100 degrees C or more under existence of the alcohol system organic compound of 100 degrees C or more of boiling points and an alkali metal hydroxide aqueous solution, and obtaining sugar sphingosine. [0014] If the boiling point of the aforementioned alcohol system organic compound is an alcohol system organic compound of 100 degrees C or more, there will be no restriction. Since heating for hydrolysis is performed at the temperature of 100 degrees C or more, the boiling point makes an alcohol system organic compound 100 degrees C or more. Preferably the boiling point of an alcohol system organic compound is 110 degrees C or more. The boiling point can mention the aliphatic alcohol compound and alicyclic alcohol compound of the carbon numbers 4 10 as an alcohol system organic compound of 100 degrees C or more, for example. As an aliphatic alcohol compound of the carbon numbers 4 10, n butanol, n pentanol, n hexanol, n heptanol, n octanol, n nonanol, n decanol, etc. can be mentioned. Cyclobutanol, cyclopentanol, cyclohexanol, cycloheptanol, cyclooctanol, etc. can be mentioned as an alicyclic alcohol compound of the carbon numbers Since especially butanol is excellent in the solubility over a ceramide saccharide, it is preferable. An alcohol system organic compound may be independent, or it may use it as a mixture. [0015] The aforementioned alkali metal hydroxide is at least 1 type chosen from the group which comprises LiOH, NaOH, and KOH, for example, and, as for alkali metal hydroxide, it is preferable that it is KOH. However, LiOH and NaOH as well as KOH can be used. The yield of the degree which the higher one of alkali metal hydroxide concentration is preferable when heating temperature is comparatively low in order to obtain high yield as a general trend, and is [ alkali metal hydroxide concentration ] also low when heating temperature is comparatively high is obtained. From such a viewpoint, alkali metal hydroxide concentration, In consideration of the kind of ceramide saccharide which is a raw material, the kind of alcohol system organic compound, heating temperature, cooking time, etc., it can determine as appropriate, and, as for an alkali metal hydroxide aqueous solution, it is selectively [ hydrolysis ] preferable for carrying out with high yield that alkali metal hydroxide concentration is more than 1M. As for alkali metal hydroxide concentration, it is more preferable that it is more than 3M, and it is much more preferable that it is less than more than 6M12M. From a viewpoint of hydrolysis, although there is no restriction in particular, the maximum of the alkali metal hydroxide concentration of an alkali metal hydroxide aqueous solution can be set to 15M, for example, if the solubility to the water of alkali metal hydroxide is taken into consideration. However, it is not the intention limited to this figure. [0016] as opposed to the amount of alkali metal hydroxide by which the amount of the alkali metal hydroxide aqueous solution used to a ceramide saccharide is needed for hydrolysis of a ceramide saccharide a large it can determine as appropriate so that it may become excessive. 3/11

4 [0017] The quantity of the alcohol system organic compound to a ceramide saccharide can be determined as appropriate in consideration of the kind of ceramide saccharide, the kind of alcohol system organic compound, heating temperature, etc., and can be determined as appropriate at hydrolysis reaction temperature in the range which a ceramide saccharide can dissolve in an alcohol system organic compound. For example, it can be considered as the range of liters of alcohol system organic compounds to 1 mol of ceramide saccharides. However, it is not the intention limited to this range. the capacity of an alcohol system organic compound the capacity of for example, an alkali metal hydroxide aqueous solution, the capacity factor range of 0.2 to 0.8: , preferably the capacity factor range of 0.4 to 0.6: more preferable, an equivalent amount is boiled substantially and it can become. [0018] The heating temperature for hydrolysis is 100 degrees C or more. Sugar sphingosine can be obtained with alternative and high yield by the heating temperature for hydrolysis being 100 degrees C or more under existence of an alcohol system organic compound and an alkali metal hydroxide aqueous solution. The heating temperature can also be 110 degrees C or more, preferably 120 degrees C or more, after also taking into consideration the boiling point of the alcohol system organic compound to be used, since the higher one realized high yield in a short time. Although it is dependent on the alcohol system organic compound to be used, the maximum of heating temperature is 200 degrees C or less practical, and is 150 degrees C or less preferably. However, it is not the intention limited to this range. A reaction turns into a reaction in a single phase easily, so that an alcohol system organic compound and an alkali metal hydroxide aqueous solution may show 2 phases and become an elevated temperature in low temperature comparatively, the reaction in a single phase tends to go on [ tend ], and a hydrolysis reaction's is preferable. [0019] Although heating of the reaction mixture for hydrolysis may be heating which used the heater, it can also be induction heating by microwave irradiation. Since a hydrolysis reaction is promoted by operation of microwave by carrying out microwave irradiation, it is preferable. Strength of microwave can be made into the range not more than 200W, for example. Microwave irradiation can be performed continuously or intermittently. [0020] There is no restriction in particular in the ceramide saccharide used as a raw material. A ceramide saccharide has the structure which a sugar residue (a monosaccharide or oligosaccharide) and fatty acid residue combined with sphingosine (SUFINGO base), and there is no limitation in each of a sugar residue (a monosaccharide or oligosaccharide) and fatty acid residue to sphingosine. A glucosyl group, a galactosyl group, etc. can be mentioned as a monosaccharide (residue) as a sugar residue. Specifically, the ceramide saccharide can be a glueosylceramide, galactosylceramide, or its mixture. [0021] Ceramide saccharides, such as a glueosylceramide, can be of natural product origin, for example, can also be a plant source or animal origin. As a plant, cereals, legumes, and corms can be mentioned, as cereals, as legumes, rice, wheat, etc. can be mentioned, a soybean etc. can be mentioned and a konnyaku potato etc. can be mentioned as corms, for example. A brain origin glueosylceramide can be mentioned as an animal origin glueosylceramide. [0022] An example of the reaction in the first modes of the present invention is shown below. A raw material is a kind of a glueosylceramide. The fatty acid which is carrying out the amide bond is hydrolyzed into a glueosylceramide using KOH, and sugar sphingosine is obtained. [0023] [Chemical formula 1] [0024] [A manufacturing method of a SUFINGO base] The second modes of the present invention is a manufacturing method of a SUFINGO base including hydrolyzing sugar sphingosine and obtaining a SUFINGO base. The aforementioned hydrolysis in this method includes making a sugar hydrolysis enzyme act on sugar sphingosine, and obtaining a SUFINGO base. [0025] The restriction in particular cannot have the sugar sphingosine used for the method of the present invention, and they can be various sugar sphingosines. Sugar sphingosine can also be the sugar sphingosine thing manufactured with the manufacturing method of the sugar sphingosine of the aforementioned present invention, for example. When sugar sphingosine is 4/11

5 the sugar sphingosine manufactured with the manufacturing method of the sugar sphingosine of the aforementioned present invention, after hydrolysis sugar sphingosine, After separating from the fatty acid which arose by the alcohol system organic compound used for the reaction, the alkali metal hydroxide aqueous solution, an unreacted ceramide saccharide, and hydrolysis, it is preferable to present the hydrolysis in the second modes of the present invention. The aforementioned separation can be performed by using chloroform:methanol:water =70:27:3 for silica gel chromatography and an elution solvent, after, extracting an amine object corresponding with chloroform methanol for example. [0026] The sugar residue of sugar sphingosine can be a monosaccharide residue or an oligosaccharide residue, and the monosaccharide residue and the oligosaccharide residue are the same as that of what was illustrated by the aforementioned ceramide saccharide. [0027] Hydrolysis of sugar sphingosine is enzymatically performed using a sugar hydrolysis enzyme. When the sugar residue of sugar sphingosine is a glucosyl group, it is suitable for a sugar hydrolysis enzyme that it is ** glucosidase. When the sugar residue of sugar sphingosine is a galactosyl group, it is suitable that it is ** galactosidase. When the sugar residues of sugar sphingosine are other sugar residues, the sugar hydrolysis enzyme which has substrate specificity is used for the sugar. [0028] The ceramide saccharide which is a raw material of sugar sphingosine is of natural product origin, and, also in a certain case, the sugar residue of the ceramide saccharide of natural product origin is solely, but the ceramide saccharide which has several different sugar residues may live together. Therefore, it is appropriate for a sugar hydrolysis enzyme to choose according to the kind of sugar residue which originates in the ceramide saccharide used as a raw material, and sugar sphingosine contains. Although sugar sphingosine is based also on the source of a raw material, a sugar residue is a glucosyl group in many cases, and, in addition to a glucosyl group, a galactosyl group may live together. The sugar sphingosine which has other sugar residues may live together. When the SUFINGO base made into the object which each sugar sphingosine has is common, the yield of the same SUFINGO base can be mentioned by hydrolyzing by using together ** galactosidase and a sugar hydrolysis enzyme in addition to ** glucosidase. [0029] The conditions of enzymatic hydrolysis can be determined as appropriate in consideration of the characteristics (substrate specificity, optimal ph, optimum temperature, etc.) of the ** glucosidase to be used or other sugar hydrolysis enzymes. Although there is no restriction in particular in the kind of sugar hydrolysis enzyme to be used, when a sugar hydrolysis enzyme is ** glucosidase, ** glucosidase of almond origin in the viewpoint that it can obtain inexpensive and easily is preferable. However, it is not the intention limited to this. When preparing ** glucosidase by using an almond as a raw material, depending on the separation refinement methods, ** galactosidase may live together in ** glucosidase. In this case, when the sugar sphingosine in which the sugar sphingosine which is a raw material has a glucosyl group as a sugar residue, and the sugar sphingosine which has a galactosyl group as a sugar residue live together, the enzyme preparations in which ** galactosidase lives together can also be used for ** glucosidase as it is. [0030] The ranges of ph are 4 6, it can carry out at the temperature of the range of degrees C, and the conditions of hydrolysis in the case of using ** glucosidase of almond origin are **. Buffer solution can be used for adjustment of ph as appropriate. Reaction time can be determined as appropriate in consideration of the kind and reaction condition of ** glucosidase to be used, for example, can be made into the range of 50 hours from 1 minute, and it is suitable for it that it is the range of 1 hour 24 hours. However, it is not the intention limited to this range. [0031] An example of the reaction in the second modes of the present invention is shown below. A raw material is a kind of the glucosyl sphingosine which is a kind of sugar sphingosine. The sugar residue which is carrying out the glycosidic linkage is hydrolyzed into glucosyl sphingosine using a sugar hydrolysis enzyme, and a SUFINGO base is obtained. The SUFINGO base can be long chain amino alcohol of the carbon number 18, and the hydrocarbon long chain can be a straight chain or branched chain including one or more unsaturation hydrocarbon chains. With origins of a ceramide saccharide, the existence of the number of unsaturation hydrocarbon chains and a position, and also branched chain changes. [0032] [Chemical formula 2] 5/11

6 [0033] Separation refinement of the SUFINGO base obtained by the aforementioned hydrolysis can be carried out by a publicly known method from reaction mixture after a reaction. Separation refinement of a SUFINGO base can be carried out by the separation refinement methods using the carrier which has a functional group which has the compatibility over the 2 amino 1,3 diol which a SUFINGO base has, for example. The functional group which has the compatibility over 2 amino 1,3 diol is glutaraldehyde, and it can carry it out using the carrier which supported glutaraldehyde, for example. It can be a thing which has the structure described below as a carrier which supported glutaraldehyde, for example. The manufacturing method of this glutaraldehyde carrier and the separation refinement methods of a SUFINGO base using a glutaraldehyde carrier are specifically shown in the reference example mentioned below. The left end of each chemical formula means a carrier. [0034] [Chemical formula 3] [Working example] [0035] Hereinafter, the present invention is described still in detail based on an working example. However, an working example is illustration of the present invention and the present invention is not the intention limited to an working example. [0036] Working example 1 KOH hydrolysis of a glueosylceramide (Joint cutting of fatty acid amide) Hydrolysis shown with the following reaction formula was carried out. The method is as follows. 1. Add barium hydroxide aqueous solution 10%, and heat on heating at reflux conditions for 22 hours, after dissolving a ceramide saccharide in dioxane and heating a solution. Dioxane: 10% barium hydroxide aqueous solution is 1:1 (capacity). Then, post processing and separation were carried out by the usual method. (50% of yield) (comparative example) 2. Add 12M potassium hydroxide solution and heat on heating at reflux conditions for 4 hours, after dissolving a ceramide saccharide in n butanol. n butanol: 12M potassium hydroxide solution is 1:1 (capacity). Then, post processing and separation were carried out by the usual method. (65% of yield) (EXAMPLE) 3. Add 12M potassium hydroxide solution and heat by microwave irradiation ization, after dissolving a ceramide saccharide in n butanol (125 degrees C). n butanol: 12M potassium hydroxide solution is 1:1 (capacity). Then, post processing and separation were carried out by the usual method (SN6 of Table 1). (92% of yield) Microwave irradiation was performed using the microwave synthesizer unit (BIOTAGE) (irradiation output: 0 400W). (EXAMPLE) [0037] [Chemical formula 4] [0038] [Table 1] 6/11

7 [0039] As shown in Table 1, joint cutting of the fatty acid amide of a glueosylceramide was attained at 85% of yield, and 92% at the temperature of 125 degrees C by using the potassium hydrate of 12M or 6M. Some starting materials with KOH concentration unreacted in the above mentioned reaction condition in 1M and 3M remained. If reaction time is extended, yield will be further inferred to become high. [0040] Working example 2 Enzymatic hydrolysis of sugar sphingosine The sugar sphingosine obtained in working example 1 hydrolyzed commercial beta glucosidase of almond origin by incubating at 37 degrees C among 0.1M sodium acetate buffer solution (ph 5) for 16 hours, and cut the glycosidic linkage. The experimental result in various enzyme concentration is shown in Table 2, and the experimental result in various ph is shown in Table 3. Commercial beta glucosidase of almond origin contains beta glucosidase and a beta galactosidase by 6:1 (mass ratio). [0041] [Table 2] [0042] [Table 3] [0043] [Chemical formula 5] [0044] 7/11

8 Working example 3 By the chemical (KOH) hydrolysis and enzymatic hydrolysis which were used as the raw material, galactosylceramide as mentioned above on the same conditions as the working examples 1 and 2 commercial beta glucosidase of almond origin, Since beta glucosidase and a beta galactosidase were contained by 6:1 (mass ratio), it checked that a sugar portion could hydrolyze not only about glucose but about galactose. Yield was 70%. [0045] [Chemical formula 6] [0046] Working example 4 On the same conditions as the working examples 1 and 2, the SUFINGO base was prepared by chemical (KOH) hydrolysis and enzymatic hydrolysis of the ceramide saccharide of the various origins. Yield is shown in Fig.1. All obtained the SUFINGO base with high yield. [Chemical formula 7] [Chemical formula 8] [Chemical formula 9] [Chemical formula 10] 8/11

9 [Chemical formula 11] [0047] Working example 5 Enzymatic hydrolysis by beta glucosidase content enzyme preparations prepared from the almond After adding acetic acid buffer solution to the commercial powdered almond and agitating for 30 minutes at a room temperature, the solid was removed by filtration cooling and after that in the refrigerator for 2 hours, and filtrate was used as crude enzyme liquid. This crude enzyme liquid was added to the sugar sphingosine prepared in working example 1, and it incubated at 37 degrees C like the working example 2 for 16 hours. The same hydrolysis ability as the working example 2 was checked. [0048] Reference example 1 A preparing method of a glutaraldehyde carrier The synthesis scheme of glutaraldehyde carrying resin (41) was shown in the following scheme 1. Alane reduction was performed to commercial (E) 3 (4 hydroxyphenyl) acrylic acid (33), and trans p coumaric acid methyl ester (34) was obtained. DDQ oxidation is carried out at coumaryl alcohol (35), trans p coumaraldehyde (36). It generated (Reference documents Kumar, N. S. S.; Varghese, S.; Narayan, G.; Das, S. Angew. Chem. Int. Ed. 2006, 45, ). The phenolic hydroxyl group of the compound 36 is protected by tert butyldiphenyl silyl ether, 1 of ethyl vinyl ether and 4 addition are performed under the hydroquinone existence of a catalyst amount, The compound 38 was obtained as a diastereomer mixture (Reference documents Longley, R. I., and Jr.; Emerson, W. S. J. Am. Chem. Soc. 1950, 72, ). Deprotection of the silylether was carried out using tetrabuthylammonium fluoride, and it fixed to Merrifield resin, without obtaining and refining the compound 39. In order to check the structure of the compound 26, comparison with the IR spectrum of the model compound 40m was performed (figure 2). [0049] [Chemical formula 12] [0050] Although the compounds 40 and 40m were in agreement by almost all IR absorption, the difference was seen near 1720 cm 1. This is a C=O stretching vibration origin spectrum of aldehyde. A part is hydrolyzed and it produces. Heat chloride performed subsequent hydrolysis in dioxane, and it succeeded in the synthesis of the dialdehyde (41) fixed to resin. [0051] The IR spectrum showed that the compound 41 was a mixture of a dialdehyde object (41a) and an annular JIHEMI acetal object (41b) (Fig.3). In spite of fixing very unstable aldehyde to glutaraldehyde carrying resin, it exists very stably. Generally, polymer ization takes place according to an aldol condensation mechanism, and glutaraldehyde is unstable. However, even 9/11

10 if it settled the IR spectrum of the compound 41 in about one year and in the room temperature, there was no change of a spectrum. This is because the distance of dialdehyde groups enlarged by having fixed to resin and self condensation was inhibited. Having taken annular JIHEMI acetal structure [ still like the annular hemiacetal structure of sugar ] (41b) whose glutaraldehyde is has contributed to stability. [0052] The support efficiency to Merrifield resin of glutaraldehyde structure was computed. The ultimate analysis of used Merrifield resin, the compound 41a obtained by synthesis, and 41b mixture was measured, respectively, and support efficiency was computed from the abundance of Cl which remains to the compounds 41a and 41b. As a result, Cl abundance ratio of Merrifield resin was %, and it was 2.74 % with the compound 41a and 41b mixture. According to support of glutaraldehyde structure in all reduction of Cl abundance before and behind a reaction, support efficiency is computed with 82.2 %. [0053] [Chemical formula 13] [0054] Scheme 1. Synthesis of the sphingosine scavenger 41 a) MeOH, Amberlite IR 120 (H + ), reflux, 45 h, 96% b) LiAlH 4 (3.5 eq.), AlCl 3 (1.2 eq.), Et2O, 0 degree C, 1.5 h, 90% c) DDQ (1.2 eq.), dioxane, r.t., 0.5 h, 81% d) TBDPSCl (1.2 eq.), imidazole (1.5 eq.), DMF, r.t., overnight, 76% e) ethyl vinyl ether (48 eq.), hydroquinone (0.3 eq.), 180 degree C, 3 d, 67% f) TBAF (1.2 eq.), THF, r.t., 3 h, 95% g) Merrifield resin (1.0 eq.), K2CO 3 (1.5 eq.), KI (0.1 eq.), DMF, 90 degree C, overnight h conc. HCl, dioxane, 60 **, 4 h [0055] Reference example 2 The capturing capacity and disconnection ability of the glutaraldehyde carrying resin (41) synthesized by the reference example 1 were considered. The IR spectrum before and behind the reaction of the resin 41 and D erythro sphingosine (1) is shown in Fig.4. [0056] [Chemical formula 14] [0057] In the THF solvent, the resin 41 was swollen, the sphingosine dissolved in methanol was added, and the prehension reaction was performed. It filtered 1.5 hours afterward, washed with methanol, chloroform, and water, and measured IR. In the IR spectrum after a reaction, the absorption of the C=O stretching vibration origin of aldehyde (near 1720 cm 1) is decreasing intentionally. On the other hand, the absorption near 2900 cm 1 of the C H stretching vibration origin of sphingosine is increasing dramatically. These change shows that prehension of the sphingosine by resin advanced. [0058] swelling resin after prehension again by THF 0.1 N chloride, 40 degrees C, it agitated for 24 hours and performed the elimination reaction. The IR spectrum was measured, after 10/11

11 filtering and washing with methanol, chloroform, and water (Fig.3). In the IR spectrum after disconnection, the spectrum near 1720 cm 1 of aldehyde origin was observed. It could check that the aldehyde which was decreasing as compared with after prehension IR had been recovered, and it was checked that the elimination reaction from the resin 41 of the sphingosine 1 had advanced. [Industrial applicability] [0059] The present invention is useful in the field about sugar sphingosine and a SUFINGO base. Previous Document 1/1 Next Do To return to the top o Notice on Usage Privacy Policy Questionnaire [Translation done.] 11/11