JPH05247081A - New tetraphenyulporphyrin glycoside and its production - Google Patents

Abstract

PURPOSE:To provide a new composition useful as a precursor for metal complexes with functions as e.g. new recording materials for photochemical hole burning, having saccharide residue having high hydrogen bond-forming ability, and excellent in solubility to solvents. CONSTITUTION:The objective porphyrin of formula I [R is of formula II (one of R1-R3 is glycoside residue of xylose, the rest being H)], e.g. 5,10,15,20-tetrakis(p-xylolphenyl)porphyrin. The compound of the formula I can be obtained by the following process: a saccharide such as xylose or glucose is acetylated and halogenated in succession, and the resulting halogenated product is made to react with an alkali salt of monohydroxybenzaldehyde to form a phenylglycoside, which is then made to react with pyrrole followed by addition of a chloranil to obtain an acetylated product of the compound of the formula I, which is finally deacetylated. The above-mentioned halogenation is preferably made by bromination of the first acetylated product with an acetic acid solution of hydrogen bromide.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a novel tetraphenylporphine glycoside having excellent solubility in organic solvents and the like.

[0002]

2. Description of the Related Art Tetraphenylporphine has been conventionally used as a model compound for a substance having a porphyrin skeleton such as hemoglobin or chlorophyll. However, since tetraphenylporphine itself is poorly soluble in an organic solvent and insoluble in water, its use is limited. Therefore, in order to make the compound soluble in an organic solvent or the like, measures such as introducing an alkyl group, a sulfonic acid group, a carboxyl group, an amino group or the like into the phenyl group in the compound have been made.

Recently, tetraphenylporphine or a derivative thereof has attracted attention as a recording material for photochemical hole burning which enables ultra-high density optical recording. However, at this stage, this photochemical hole burning recording is possible only at extremely low temperatures,
Therefore, raising the operating temperature is one of the practical problems. Up until now, there have been few successful high-temperature operations, and K.Sa
koda, K. Konamimi, and M. Iwamoto, Jpa. J. Appl. Phy
s., 27, L1304 (1988). and K. Horie, T. Mori, T. Ta.
kuya, and I. Mita, Appl. Phys. Lett., 53, 935 (198
8). It is considered that the factor of successful operation at these high temperatures is due to the hydrogen bond between the dye and the matrix, and the development of more excellent recording materials that enable higher temperature operation is awaited. On the other hand, as tetraphenylporphine glycosides, P. Maillard, J.-LG-Kern, M. Momenteau, and
S. Gaspard, J. Am. Chem. Soc., 111, 9125 (1989).
In the above, only an example of synthesizing helicin as a raw material is shown.

In recent years, porphyrin derivatives have been used as a therapeutic material for photodynamic therapy, and some clinical cases have been reported. In this case, there are drawbacks in that it is very slow in terms of solubility until it is taken into the body, and that the time required for treatment is long and the patient is burdened. From these points, a porphyrin derivative having excellent absorbability and safety is desired. Furthermore, although various metal complexes of porphyrin derivatives have been investigated as organic synthesis reaction catalysts, their application range may be dramatically expanded by improving their solubility. For these reasons, there is a need for a porphyrin derivative that can easily obtain a metal complex.

[0005]

DISCLOSURE OF THE INVENTION The object of the present invention is to meet the above-mentioned needs, and to provide tetraphenyl having a sugar residue having a strong hydrogen-bonding ability and exhibiting high solubility in a solvent or the like. It is to provide a porphine glycoside. Since the compound of the present invention has a sugar residue, extremely excellent effects such as absorbability and safety can be expected. Also,
The metal complex of the tetraphenylporphine derivative can be easily obtained from the compound of the present invention.

[0006]

The present inventors have provided a novel recording material for photochemical hole burning, a therapeutic agent as a photodynamic therapy, or a precursor of a tetraphenylporphine metal complex having a function as a catalyst. In view of the above, the present invention has been completed as a result of earnest studies on porphine compounds. That is, the present invention is
General formula (I)

[Chemical 3] [Where R is the following formula

[Chemical 4] (In the formula, _one of R ₁ , R ₂ and R ₃ represents a glycoside residue of xylose, and the rest represent hydrogen atoms.)
Represents a phenyl glycoside residue represented by. ] It is related with the novel tetraphenylporphine glycoside compound represented by these, and the manufacturing method of this compound. The tetraphenylporphine glycoside compound of the present invention has an α- or β-form depending on the substitutional configuration on the anomeric carbon atom of the glycoside residue, and the present invention includes either or both of them.

The compound represented by the general formula (I) of the present invention can be synthesized by combining the methods known per se, but the following method can be most efficiently synthesized. First, as a method for acetylating sugars such as xylose and glucose, APNFranchimont, Ber., 12, 1938 (187
9)., E. Fischer, Ber., 49, 584 (1916)., R. Behrend a
nd P. Roth. Ann., 331, 359 (1904)., CS Hudson a
nd JK Dale, J. Am. Chem. Soc., 37, 1264 (1915).
Although there is a method shown in the above-mentioned documents, the present inventors used the method shown below. That is, xylose or glucose is acetylated with acetic anhydride using anhydrous sodium acetate as a catalyst to obtain acetate.

Next, when the glycoside is synthesized, the acetylated product is halogenated and used. Various halogens can be used, but bromine (bromine) is the most efficient and is a bromination method. Is M. Barcza
i-Martos and F. Korosy, Nature, 165, 369 (1950).,
RU Lemieux, Methods Carbohydr. Chem., 2, 221,22
Although there is a method described in the literature such as 3, 224 (1963)., The present inventors used the method shown below. After dissolving the above-obtained acetate in chloroform, the anomeric carbon atom is brominated with a hydrobromide acetic acid solution.

The bromide obtained above is reacted with an alkali salt of monohydroxybenzaldehyde such as sodium salt in acetone to obtain phenylglycoside. The method using this monohydroxybenzaldehyde is as described above.
Compared with the method using helicine as a raw material shown in J. Am. Chem. Soc., 111, 9125 (1989)., The advantage is that a relatively easily available industrial raw material called monohydroxybenzaldehyde can be used. And the substitution position (o-, m
-, P-) can be arbitrarily changed by selecting a monohydroxybenzaldehyde raw material, helicine is only glucose, but sugar of glycoside can be selected, and helicin is a natural product. Although it can be obtained, its productivity is not good because purification is difficult. As described above, the manufacturing method of the present invention has various excellent characteristics. For reference, as a method for obtaining a glycoside compound, N.
Kornblumand AP Lurie, J. Am. Chem. Soc., 81, 270
5 (1959)., H. Paulsen, Angew.Chem. Int. Ed. Engl.,
21, 155 (1982)., K. Igarashi, Adv. Carbohydr. Che
m. Biochem., 34, 243 (1977)., G. Wulff, R. Rohle,
and W. Kruger, Chem. Ber., 105, 1097 (1972)., L.
R. Schroder and JW Green, J. Chem. Soc., 1966,
530., T. Torii, T. Tsuchiya, I. Watanabe, and S. Um
ezawa, Bull. Chem. Soc. Jpn., 55, 1178 (1982)., H.
M. Flowers, Methods Carbohydr. Chem., 6, 474 (197
2)., RU Lemieux and WR Morgan, Can. J. Che
m., 43, 2199 (1965)., M. Mazurek and AS Perlin,
Can. J. Chem., 43, 1918 (1965)., S. Hanessian and
J. Banoub, Methods Carbohydr. Chem., 8, 247 (198
0)., F.Austine, FE Hardy, JG Buchanan, and
J. Baddiley, J. Chem. Soc., 1964, 2128., FJ Kro
nzer and C. Schuerch, Carbohydr. Res., 27, 379 (19
73)., S. Hanessian and J. Banoub, Carbohydr. Res.,
53, C, 13 (1977)., PJ Garegg and T. Norberg, A
cta Chem. Scand., Ser. B., 33, 116 (1979)., H. Paul
sen and C. Kolar, Chem. Ber., 114, 306 (1981)., A.
Knochel, G. Rudolph, and J. Thiem, Tetrahedron Le
tt., 1974, 551., A. Knochel and G. Rudolph, Tetrah
edron Lett., 1974, 3739., J. Conchie and GA Lev
vy, Methods Carbohydr. Chem., 2, 332, 335 (1963).,
EA Talley, Methods Carbohydr.Chem., 2, 337 (196
3)., K. Igarashi, J. Irimajiri, and T. Honma, Carb
ohydr. Res., 39, 341 (1975).

Next, a cyclization reaction is carried out with the phenyl glycoside and pyrrole. As this type of cyclization reaction,
AW van der Made, EJH Hoppenbrouwer, RJ
M. Nolte, and W. Drenth, Recl. Trav. Chim. Pays-Ba
s, 107, 15 (1988)., JS Lindsey, HC Hsu, and
IC Schreiman, Tetrahedron Lett., 27, 4969 (198
6)., A. Treibs and N. Haberle, Liebigs Ann. Chem.,
718, 183 (1968)., AD Adler, FR Longo, JD
Finarelli, J. Goldmacher, J. Assour, and J. Korsa
koff, J. Org. Chem., 32, 476 (1967)., AD Adler,
FR Longo, and W. Shergalis, J. Am. Chem. Soc.,
86, 3145 (1964). And the like, which are recognized to be applicable to the method for producing the compound of the present invention, the following method was used in the present invention. The phenylglycoside obtained above and pyrrole are reacted in dry dichloromethane using a boron trifluoride diethyl ether complex as a catalyst, and then chloranil is added to carry out the reaction to obtain the acetyl compound of the general formula (I). Get the compound. Then, deacetylation is carried out in methanol / dichloromethane using sodium methoxide as a catalyst to obtain the compound represented by the general formula (I).

The compound represented by the general formula (I) of the present invention is a dark red solid at room temperature and atmospheric pressure. In its visible spectrum there are the Sole and Q bands characteristic of porphyrins. It also dissolves very well in solvents and the like. As can be seen from the above-mentioned production method, the compound of the present invention has two types of α- or β-rotationally hindered isomers due to the anomeric carbon atom. Depending on the raw material compound used, either the α- or β-form or a mixture of the two is obtained. In the present invention, as the saccharides such as xylose and glucose which are the starting materials, saccharides known in the field of this kind can be used for the reaction, and tetraphenylporphine glycosides corresponding to the used saccharides can be obtained. You can Since the compound of the present invention has a sugar residue, extremely excellent effects such as absorbability and safety can be expected. Further, the metal complex of the tetraphenylporphine derivative can be easily obtained from the compound of the present invention.

[0012]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited thereto. Example 1 Xylose 50.0 g (0.333 mol) and sodium acetate 25.0 g
Add 272.0 g (2.66 mol) of acetic anhydride to (0.305 mol),
The mixture was stirred at 100 ° C for 4 hours. The reaction solution was cooled to room temperature, water was added to the reaction solution, and the mixture was extracted with dichloromethane. The dichloromethane extract was washed with a saturated aqueous solution of sodium hydrogen carbonate. Further, after washing with water, the dichloromethane layer was separated. Anhydrous sodium sulfate was added to this dichloromethane solution for drying. After distilling off the solvent, it was recrystallized from ethanol. The crystals were vacuum dried to obtain 57.0 g of tetra-O-acetylxylose.

7.50 g (0.0277 mol) of phosphorus tribromide was added to 20 parts of acetic acid.
1.40 g of water (0.0778 m
ol) was added dropwise. After completion of dropping, stirring was continued at room temperature for 30 minutes. This solution was added to tetra-O-acetylxylose 16.2.
g (0.0511 mol) was added to a solution prepared by dissolving 30 ml of chloroform, and the mixture was stirred at room temperature for 4 hours. Water was added to the reaction solution, which was extracted with dichloromethane. The extract was washed with water and then with a saturated aqueous solution of sodium hydrogen carbonate. Furthermore, after washing with water, the dichloromethane layer was separated, and anhydrous sodium sulfate was added and dried. After distilling off dichloromethane, recrystallization from diethyl ether-petroleum ether to give tri-O-
14.91 g of acetyl xylosyl bromide was obtained.

Tri-O-acetyl xylosyl bromide 1
80 ml of acetone to 0.14 g (0.0300 mol) and sodium salt of p-hydroxybenzaldehyde 6.49 g (0.0450 mol)
Was added and the mixture was stirred at 50 ° C. for 2 hours. Water was added to the reaction solution, which was extracted with dichloromethane. The extract was washed with a 5% aqueous sodium carbonate solution and then with a saturated aqueous sodium chloride solution. The dichloromethane layer was separated, dried over anhydrous sodium sulfate. After distilling off dichloromethane,
By silica gel column chromatography, eluting with 5% acetone-dichloromethane, 8.00 g of p-formylphenyltri-O-acetylxyloside was obtained.

4.75 g (0.0125 mol) of p-formylphenyltri-O-acetylxyloside and 0.85 g of pyrrole (0.
(0127 mol) was dissolved in dry dichloromethane and then purged with nitrogen for 10 minutes. Boron trifluoride / diethyl ether complex 0.25 g of diethyl ether solution was added, and the mixture was reacted at room temperature for 1 hour. 3.10 g (0.0126 mol) of chloranil was added and refluxed for 1 hour. After concentrating the reaction solution, the resulting crude product was subjected to silica gel column chromatography to obtain 5% acetone-
By eluting with dichloromethane, the target acetylated product was collected. Perform the above silica gel column chromatography again to obtain a dark red solid that is the acetylated product of interest.
0.747 g was obtained. 135 mg of this solid was dissolved in 4 ml of 50% methanol-dichloromethane, one drop of 28% sodium methylate methanol solution was added, and the mixture was reacted at room temperature for 10 minutes.
The precipitated solid was filtered under reduced pressure and dried under vacuum to obtain 5,10,15,
76 mg of 20-tetrakis (p-xylosylphenyl) porphyrin was obtained. The nuclear magnetic resonance spectrum of the obtained porphyrin is shown in FIG.

Example 2 Using the sodium salt of o-hydroxybenzaldehyde in place of the sodium salt of p-hydroxybenzaldehyde, the same synthetic method as in Example 1 above was used.
5,20-Tetrakis (o-xylosylphenyl) porphyrin was obtained. Here, it was confirmed by thin layer chromatography at the stage of the porphyrin of the acetylated product that two types of rotationally hindered isomers exist. The nuclear magnetic resonance spectrum of the obtained porphyrin is shown in FIG. 2, and this spectrum is either one of the rotationally hindered isomers or a mixture.

Example 3 Using the sodium salt of m-hydroxybenzaldehyde in place of the sodium salt of p-hydroxybenzaldehyde, the same synthetic method as in Example 1 above was used.
5,20-Tetrakis (m-xylosylphenyl) porphyrin was obtained. Here, it was confirmed by thin layer chromatography at the stage of the porphyrin of the acetylated product that two types of rotationally hindered isomers exist. The nuclear magnetic resonance spectrum of the obtained porphyrin is shown in FIG. 3, and this spectrum is either one of the rotationally hindered isomers or a mixture.

[Brief description of drawings]

1 is a chart of ¹ H-nuclear magnetic resonance spectrum of the tetraphenylporphine xylose glycoside obtained in Example 1. FIG.

FIG. 2 is a chart of ¹ H-nuclear magnetic resonance spectrum of the tetraphenylporphine xylose glycoside obtained in Example 2.

FIG. 3 is a chart of ¹ H-nuclear magnetic resonance spectrum of the tetraphenylporphine xylose glycoside obtained in Example 3.

Claims (4)

[Claims] 1. The following general formula (I): [Wherein R is the following formula: (In the formula, _one of R ₁ , R ₂ and R ₃ represents a glycoside residue of xylose, and the rest represent hydrogen atoms.)
Represents a phenyl glycoside residue represented by. ] The novel tetraphenylporphine glycoside compound represented by these. 2. Acetylation of saccharides such as xylose and glucose, followed by halogenation to form a halide, the halide being reacted with an alkali salt of monohydroxybenzaldehyde to obtain phenylglycoside, and the phenylglycoside being reacted with pyrrole. Then, chloranil is added to obtain an acetylated product of the compound represented by the general formula (I), and the obtained acetylated product is deacetylated to obtain a compound represented by the general formula (I). 3. The production method according to claim 2, wherein any one of para, meta and ortho isomers is used as a raw material as the monohydroxybenzaldehyde. 4. A bromide obtained by brominating the anomeric carbon atom of an acetylated product of xylose with a hydrobromic acid acetic acid solution is used as a halide obtained by acetylating a saccharide and then halogenating it. Item 2. The manufacturing method according to Item 2 or Item 3.