JPS60190786A - Saccharide derivative - Google Patents

Abstract

NEW MATERIAL:A compound shown by the formula I [S is residue after removal of n HO from saccharide or sugaralcohol; A is O, NH, or OCO; X is H, or oxyl; R1 and R2 are H, linked to form one group; m is 0, or 1; n is 1-10]. EXAMPLE:1-(2,2,6,6-Tetramethyl-4-piperidyl)glucose. USE:A photostabilizer for organic material, etc. PREPARATION:For example, 66wt% NaH-mineral spirit solution is added little by little to 2,2,6,6-tetramethyl-4-hydroxypiperidine in DMF under cooling with ice, they are stirred at room temperature for 1hr, and it is reacted with 1- chloro-1-deoxy-2,3,4-6-tetraacetyl glucose. After the reaction product is isolated, it is deacetylated, to give 1-(2,2,6,6,-tetramethyl- 4-piperidyl)glucose shown by the formula II.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides a novel sugar derivative having a hindered amine group, specifically, a light stabilizer for use in organic materials such as synthetic polymers or an intermediate thereof, or a biologically related substance or an intermediate thereof. The present invention relates to a sugar derivative having a hindered amine group.

2.2.6.6-thitraalkylbiveridine compound 2,
2.6.6-Titraalkylbiroline or pyrrolidine compounds are known as light stabilizers for various organic materials including synthetic polymers such as polyolefins, polyurequins, and styrenic resins.

For example, in Japanese Patent Publication No. 46-426'18, 2゜2.
6,6-tetramethyl-4-piperidyl alkyl ether is described, and 2,2
, 6,6-tetramethyl-4-aminopiperidines are described, and US Pat. No. 4,064,102 describes 2,2
．． 6,6-tetramethyl-4-piperidinecarboxylic acid ester is described, and 2,2,5,5-tetramethylpyrorinse is described as pyrrolidinecarboxylic acid ester in US Pat. No. 4,111,901.

However, when the compounds described in these publications are used as light stabilizers for organic materials, their effects are rapidly lost during compounding or use, and as a result, they do not stabilize the tatable materials for a long period of time. I couldn't.

In view of the current situation, the present inventors conducted intensive research and found that a new sugar derivative having a specific hindered amine group is extremely excellent as a light stabilizer for organic materials.

The present invention was made based on the above findings, and provides a sugar derivative having a hindered amine group, represented by the following general formula (1).

[In the formula, ■ is from sugar or sugar alcohol.
Residues other than the hydroxyl group are not shown. A represents -0-11 -NH- or -0C-. X represents a hydrogen atom or oxyl (-0.). R1 and R2 represent a hydrogen atom or jointly represent a direct bond. m indicates 0 or 1.

n represents 1 to 10. ] The sugar derivative of the present invention represented by the above general formula (I) is useful as a light stabilizer for organic materials or an intermediate thereof, or as an active ingredient for pharmaceuticals or agricultural chemicals, or as an intermediate thereof. .

The sugar derivative of the present invention will be explained in detail below.

In the sugar derivative of the present invention represented by the general formula (1), the sugar or sugar alcohol residue represented by (■) includes arabinose, ribose, xylose, fladi
Residues of sugars such as galactose, glucose, mannose, sorbose, glucoheptose, lactose, maltose, sucrose, trehalose, melezuitose, raffinose, stathiose, dextrin, cyclodextrin, glycogen, and treinod, erythritol, aravit, ribinot, xylit , sorbit, manninto, ijituto, talisoto, zurcit,
Examples include residues of sugar alcohols such as Alit.

The sugar derivative of the present invention represented by the general formula (1) can be easily produced by a method commonly used for etherification, amination, or esterification of sugars.

The present invention will be explained in more detail below by giving Examples showing the production of the sugar derivative of the present invention represented by the general formula (1), but the present invention is not limited by these Examples. .

Example 1 2.2,6.6-tetramethyl-4-hy 1-1゛! 3.14 g of xypiperidine was dissolved in 1" dimethylformamide, and to this was added 0.9 g of 66% hydrogenated 1-1" mineral spirit/8 solution in small portions under cooling with water, and the mixture was heated at room temperature for 1 hour. To this, 1-di-1-C1--1-deoxy-2,3, which had been synthesized in advance by reacting penquacetyl glucose and aluminum chloride according to a conventional method, was added.
, 6.96 g of 4,6-te1-laacetylglucose were added little by little under ice-cooling. After stirring this at room temperature for 5 hours, the solvent was distilled off, the solution was dissolved in water, and extracted with chloroform. The chloroform layers were combined, dried, and then the solvent was removed to obtain a pale brown liquid. From the liquid, the target compound was fractionated as a tetraacetyl compound using a silica gel column using toluene/ethyl acetate as a developing solvent. After dissolving this in anhydrous methanol, it was hydrolyzed with a 28% sodium methoxide-methanol solution.

After that, after removing the solvent, extract with chloroform and remove the solvent f&n.
-Washing with hexane gave a slightly yellow powder product (target compound).

Melting point: 74-76°C Elemental analysis: CHN Measured value (%) 56.89 9.18 4.35 Calculated value (%) 56.41 9.15 4.39 Structural formula: Example 2 2.2.6. 6-Tetramethyl-4--H(1:+2.2,6.6-Te1-ramethyl-4-hydroxypiperidine=■-oxyl instead of 3,44
A product in the form of orange crystals was obtained in the same manner as in Example 1 except that g was used. Thereafter, the product was recrystallized from toluene/n-hexane.

Melting point: 67.5-68.5℃ Uv: λ243 8-2410 Elemental analysis: C, HN Measured value (%) 53.06 9.01 4.18 Calculated value (%) 53.88 8.44 4.19 Structural formula: An orange powder product was obtained in the same manner as in Example 2, except that 5.60 g of 1-chloro-1-deoxy-2,3°4-triacetyl ribose was used as the saccharide.

Melting point: 69.0-70.0°C Uv: λ241 ε-2180 Elemental analysis: HN Measured value (%) 53.99 9.00. 1.66 Calculated value (%) 55.25 '8.61 4.60 Structural formula: 1-chlorohebutaacetylmaltose 1 t
The product was obtained as a rWi tan powder.

Melting point: 81.0-81.5°C Elemental analysis: C H N Measured value (%) 53.44 9.01 2.47 Calculated value (%) 52.38 8.16, 2.91 Structural formula: As a saccharide 1-chloroheptaacetylmaltose 1 2
．． A product of orange crystals was obtained in the same manner as in Example 2 except that 44 g was used.

Melting point: 66, o~68.0°C Uv: λ245 8-1985 Elemental analysis: HN Measured value (%) 49.79 8.11 2.79 Calculated value (
%) 50.50 7.71 2.82 Structural formula: Example 6 1.8 g of anhydrous glucose was suspended in dry dimethylpolamide, and under water cooling, 2,2,6.6--teI-ramethyl-
After adding 1.9 g of 4-aminopiperidine little by little,
It was heated to 40-50°C to completely dissolve glucose. After stirring at 80°C for 2.5 hours, the solvent was distilled off under reduced pressure to obtain a colorless syrup. Acetone was added to precipitate crystals, which were then filtered, washed with acetone, and dried to obtain a white powder product.

Melting point: 4o, s ~ 44.5°C IR: 1670 cm' (absorption based on NH) Elemental analysis: HN Measured value (%) 54.95 9.08 B, 85 Calculated value (
%) 56.5B 9.50 8.80 Structural formula: %Formula% Except for using 2.1 g of 4-amino-2,2,Ei, 6-tetramethylbiveridin-1-oxyl in place of veridine. An orange powder product was obtained in the same manner as in Example 6.

Melting point: 3B to 44°C UV: λ243 ε-2320 Elemental analysis: HN Measured value (%) 53.64 9.12 8.08 Calculated value (%) 54.04 8.77 8.40 Structural formula: Ribose as sugar A white powder product was obtained in the same manner as in Example [j except that .

Melting point: 50-53°C Elemental analysis: HN Measured value (%) 57.98 10.37 9.33 Calculated value (%) 58.31 9.79 9. '71 structural formula: ffM An orange powder product was obtained in the same manner as in Example 7 except that ribose was used as the cheek.

Melting point: 47-51°C UV: λ23t ε= 2410 Elemental cumulative element CHN Measured value (%) 55.76 9.38 9.17 Calculated value (%) 55.43 8.97 9.23 Structural formula: Example 10 A white powder product was obtained in the same manner as in Example 6 except that maltose was used as the saccharide.

Melting point: 79-81°C Elemental analysis: HN Measured value (%) 53.00 8.91 5.80 Calculated value (%) 52.49 B, 39 5.83 Structural formula: Except for using maltose as #i group An orange powder product was obtained in the same manner as in Example 7.

Melting point: 73-78°C Uv: λ2to1 ε-1980 Elemental analysis: HN Measured value (%) 49.81 8.06 5.84 Calculated value (%) 50.90 '7.93 5. ．． 65 Structural formula: %Formula% Methylpiperidine-4-carboxylic acid methyl ester2.
4 g and 80 mg of lithium amide were dissolved in dimethylformamide and heated at 90°C under a reduced pressure of l Q Qmm fig.
The mixture was stirred for 15 hours. Benzene was added, and the precipitated crystals were filtered, washed with water, and dried to obtain the product Ir, 7.

Melting point = 62-65°C IR: 1720 cm-1, 3430 cm-1 Elemental analysis: C) I N Measured value (%) 56.05' 8.19 3.93 Calculated value (%) 56.78 8.58 4. 14 Example 13 1.86 g of diisopropylidene-D-glucose and pyridine], 14 g of benzene 20+n! dissolved in
1-oxyl-2,2,6,6--ketramenal-4-
2.58 g of piperidine carboxylic acid chloride I' was added dropwise. After the dropwise addition, the mixture was stirred at 60°C for 15 hours, the precipitated salt was filtered off, and the solvent was distilled off. After adding ether to the residue and dissolving it,
a 20 ml of hydrochloric acid was added, and the mixture was stirred at room temperature for 2 hours. The aqueous layer was taken, neutralized with heavy sodium chloride water, and then dried. After extraction with ethyl acetate, treatment with ether gave the product as a tan powder.

Melting point: 93-97°C Uv: λ245 8=2130 Elemental analysis: HN Measured value (%) 52.75 7.71. 3.78 Calculated value (%) 53.04 7.73 3.81 Example 14 Diisopropylidene-D-glucose 2. Og, 2.2
．． 2.2 g of 5.5-tetramethylpyrrolidine-3-carboxylic acid methyl ester and 0.08 g of lithium amide
The mixture was heated and stirred in xylene while removing generated methanol. After washing with water, the solvent was distilled off, and 10 ml of dioxane and 10 ml of concentrated hydrochloric acid were added to the residue, followed by stirring at room temperature for 2 hours. The aqueous layer was separated, neutralized with sodium hydrogen aqueous solution, condensate was distilled off, and then extracted with chloroborum to obtain a slightly yellow solid product.

Melting point: 115-118℃ IR: 1720cm (,3420cm-1 Elemental analysis: CI(N Measured value (%) 53.378. o44. o.

Calculated value (%) 54.05 7.80 4.20 Example 15 2,2I5.5-tetramethylpyrrolidine- instead of 2.2,6.6-tetramethylbiveridine-4-carboxylic acid methyl ester 3-monocarboxylic acid methyl ester 2
．． The procedure was repeated in the same manner as in Example 12, except that 2 g was used, and the slightly yellow solid product was jSi.

Melting point = 71-74°C IR: 1720 cin-', 3-430 cm-' Elemental analysis: HN Measured value (%) 54.81 7.94 4.08 Calculated value (%) 55.53 8.33 4.31 Example 16 1-Oxyl-2,2,5,5-tetramethylbiroline-3-carboxylic acid chloride 2 instead of 1-oxyl-2,2,6,6-tetramethyl-ri-piperidinecarboxylic acid chloride A yellowish brown powder product was obtained in the same manner as in Example 13, except that .4 g was used.

Melting point: 105-107°C IR: 1045cm-', 1720cm-Gourd 34
20cm-1UV' 7i246 s -1900 Elemental analysis: C'HN Measured value (%) 51.44 6.92 3.85 Calculated value (%) 51.72 6.90 4.02 Example 17 Sucrose 0.9' Take 3 g of pyridine, 0.56 ml of pyridine and 20 ml of dimethylbormamide, and add dimethyl of 1-oxyl-2,2,5,5-tetramer viroline-3-carboxylic acid chloride I', 21; A formamide solution was added dropwise, and the mixture was stirred at room temperature for 5 hours. The solvent was distilled off under reduced pressure, and the residue was washed with benzene and then extracted with ethyl acetate. The ethyl acetate was distilled off to remove the yellow-brown semisolid product.

U■: λ243 6=2560 Elemental analysis: C! -IN Measured value (%) 52. ．． 39 6.79 3.711 Calculated value (%) 53.41 6.82 4.15 Example 1
8 Take 1.82 g of sorbitol, 3.3.2 g of pyridine and 40 ml of dimethylformamide, and add 1-
A dimethylformamide solution of 7.87 g of oxyl-2,2,6,6-titramethylpiperidine-4-carboxylic acid chloride was added dropwise and stirred at room temperature for 5 hours. A tan solid product was obtained.

Softening point 2 60~75℃ U~': λ246 8-2360 Elemental analysis: C1,N Measured value (%), 58.61 B, 49 5.56 Calculated value (%) 59.34 8.52 5.77 Example 17 Take 0.68 g of sucrose, 1.52 g of pyridine and 20 ml of dimethylforma, and add 1-
Oxyl-2,2,5,5-tetran(-ruvirorin-
A solution of 3.89 g of 3-carboxylic acid chloride in dimethylformamide was added dropwise, and the mixture was stirred at room temperature for 1 hour.

Thereafter, the same treatment as in Example 17 was carried out to obtain a yellowish brown solid product.

Melting point = 8B~95℃ U■: λ243 ε=3140 Elemental analysis: CHN Measured value (%) 59.45 7n 6.311 Calculated value (
%) 60.36 7.07 6.71 Next, the t! of the present invention! The effect of the i derivative will be specifically explained using an experimental example.

Experimental Example 1 This experimental example shows the effect of the sugar derivative of the present invention as a light stabilizer for organic use.

100 parts by weight of polypropylene, stearyl-β-3,5
-G-tert-butyl-4-human-1koxyphenylprobione-1-0.2 parts by weight and sample compound (see Table 1) 0
．． Using 3 parts by weight, a sheet having a thickness Q of 3 mm was produced by press working. A light resistance test was conducted using this sheet using a high-pressure mercury lamp. The results are shown in Table 1 below.

Table 11 Experimental Example ■ In order to examine the action of the sugar derivative of the present invention as a biologically relevant substance, the sensitizing effect of thymine upon radiation irradiation was measured.

In a Pyrex test tube, 5 ml of physiological saline containing 1 mmol of thymine and 0.5 meq. rad/h
) was irradiated with gamma rays. After irradiation, the solution was analyzed by high performance liquid chromatography (LC-3A) to confirm the product. The results are shown in Table 2 below.

In addition, in the table, ■ indicates the amount of decrease in thymine (mmol), and ■ indicates the amount of decrease in thymine (mmol).
．． 6-Sihitro 5.6-Sihi IS The production M (mmol) of Roxithymine is shown, and ■ indicates the production amount of 5-Hi10-oxymethyluracil.

Table 2 Conventionally, in cancer radiotherapy, it was thought that the DNA itself was cleaved by irradiating cells, but in recent years, hydroxylation of thymine in DNA has led to changes in its three-dimensional structure. It is estimated that it will collapse and cease to function.

It has been confirmed that thymine is not easily hydroxylated even when irradiated with radiation in an anoxic state, and cancer cells receive almost no oxygen supply from the blood, so they are in an anoxic state, and radiation exposure in actual cancers is difficult. The above assumption is also supported by the fact that cancer cells are not destroyed in treatment unless a sensitizer is administered.

As shown in Table 2, the sugar derivative of the present invention significantly promotes hydroxylation of thymine, and is expected to be applied to the treatment of cancer.

Patent applicant ADEKA ARGUS CHEMICAL CO., LTD. Continuation of page 1 ■ Inventor Ryoji Kimura @ Inventor Hi 1) Etsuo Yoshisha [5-2-13 Shirahata, Waichi Adeca Argus Chemical Co., Ltd., Waichi 5-2-13 Shirahata ADEKA ARGUS CHEMICAL CO., LTD.

Claims (1)

[Scope of Claims] A sugar derivative having a hindered amine group, represented by the following general formula (I). [In the formula, ■ is n + 111 in the order of sugars or sugar alcohols.
The residues of No. 11 with the hydroxy group removed are shown. Aba10-1
1 -NH- or -OC-. X does not represent a hydrogen atom or oxyl (-〇.). R1 and R2 represent a hydrogen atom or jointly represent a direct bond. Bars indicate O or 1. n represents 1 to 10. ]