JPS603400B2 - Method for producing 3-deoxy-3-iodo-D-glucose derivative - Google Patents

Description

[Detailed description of the invention]

The present invention is based on the general formula

[0] This invention relates to a method for producing a 3-deoxy-3-yodo-D-glucose derivative represented by the formula (wherein R2 represents a hydrogen atom or an acyl group). The compound of general formula m] which is the object of the present invention is a substance known as an X-ray contrast agent when R2 is a hydrogen atom, and when R2 is an acyl group, it can be easily hydrolyzed to convert into a hydrogen atom. It is a new substance that is useful as an intermediate for the production of an X-ray contrast agent, and is also expected to be useful as an X-ray contrast agent itself. Conventionally, the method for producing 3-deoxy-3-yodo-D-glucose [formula [m]] involves using a glucofuranose derivative [formula [W]] as a starting material and subjecting it to oxidation and reduction steps, as shown in the reaction formula below. Allofuranose derivatives [
A method is known in which after formula [V] is derived, the compound is iodinated and then hydrolyzed. However, in each of the above formulas [W] and [V], R3 and R4 represent a lower alkyl group, and R5 represents a hydrogen atom, an alkylsulfonyl group, or an arylsulfonyl group. ) However, this method is not necessarily an industrially advantageous method because the raw materials used in the oxidation/reduction step are expensive and there are various difficulties in the iodination reaction conditions of the compound of formula [V]. I can't say that. In order to overcome the drawbacks of these conventional methods, the present inventors have found that by reacting the compound represented by the general formula [1] with an alkali metal bromide in an aprotic solvent, the general formula [1] D] was successfully obtained easily. (In the formula, R represents an alkylsulfonyl or arylsulfonyl group, and R2 represents a hydrogen atom or an acyl group.) In the compound of the starting material [1] used in the present invention, R represents an alkylsulfonyl or arylsulfonyl group. Among them, methylsulfonyl, benzenesulfonyl, P-toluenesulfonyl, benzylsulfonyl, etc. are particularly preferred, and methylsulfonyl and P-toluenesulfonyl are particularly preferred. Further, the compound of general formula [1] is described in Journal Chemical Society; 1960 Wang, p. 2236-19. and Carpohydrate Research; Volume 24, 1972 King, 1
54-8 pages. Manufactured according to etc. The alkali metal iodine used as the oxidation reagent is lithium iodide, sodium iodide, and potassium iodide, with sodium iodide being preferred. The appropriate amount of alkali metal powder used in the iodination reaction is 2 to 5 times the molar amount of the compound of general formula [1] as a raw material. Examples of the non-brotic polar solvent used in the present invention include dimethylformamide, dimethylsulfoxide, tetramethylurea, hexamethylphosphorylamide, and the like. The reaction temperature and reaction time can be arbitrarily selected based on the above composition, but 80 to 130°C and 4 to 2 hours are suitable. Also - general formula

After crystallizing the target compound [0], the unreacted raw materials remaining in the mother liquor can be recovered as the target compound of general formula [B] by subsequently treating the mother liquor with an alkali metal bromide. Ru. In addition, the compound in which R2 in the general formula [b] is an acyl group can be converted into 3-deoxy-3-yodo-D-glucose shown by the formula [m] by hydrolyzing with an acid according to a conventional method, if desired. . Next, the present invention will be explained with reference to examples, but the present invention is not limited to the following examples. Example 11,2,4,6-tetra-0-acetyl-3
Synthesis of -deoxy-3-iodo-8-D-glucopyranose 1,2,4,6-tetra-○-acetyl-3-
A mixture of Z containing 2.09 (3.98 hm. 1) of toluene-P-sulfonyl-8-D-glucopyranose, 1.8 mol (12 hmol) of sodium iodide, and 8.0 mol of dimethylformamide was prepared at 130 qo.
Praise the unique lantern. At the end of the reaction, thin layer chromatography was performed [thin layer plate: Silica gel A95715 manufactured by Merck & Co., Ltd.] was used. After confirming with developing solvent; benzene:ethyl acetate (3:1) and isopropyl ether:benzene (4:1)], the reaction solution was concentrated under reduced pressure, extracted with ethyl acetate, and diluted with 1% thiosulfuric acid. After washing with sodium and water, drying with anhydrous sodium sulfate, removing the desiccant and concentrating under reduced pressure, inpropyl alcohol is added to crystallize. After collecting the crystals (1.0 min.), the mother liquor was concentrated under reduced pressure, and the resulting syrup (0.6 min.) was added with sodium iodide (0.5 min.) and dimethylformamide (3.0 min.).
) was added, the reaction was carried out again under the same conditions, and 0.3 crystals were obtained by processing in the same machine. 1.3 hours in total for both (yield 72%) Melting point 118-9o, [a]. =1200 (Cヱ1, chloroform) elemental analysis value C,
Actual value C: 36.71H: 4.17 Calculated value C: 36.71H: 4.17 N, M, R, spectrum 6 5.631 days d J,, 2 8Hz H-15
．． 291st d, d, J2,3 11HZ H-24.
801 days t J3,4 11HZ H-35281 days m J4.5 9HZ H-4 Example 2 1,2,4,6-tetra-10-penzoyl-3-deoxy-3 days Synthesis of iodo-181D-glucopyranose 1 ，
2,4,6-tetra10-penzoyl-3-deoxy-
Synthesis of 3-iodo BD-glucopyranose 1,2,
4,6,1-tetrauo-penzoyl-3-0-(P-toluenesulfonyl)-18-D-glucopyra/ase 2.0
Sodium iodide (2.7 mm. 1), sodium iodide 1.6 mm (10.7 mmol)
, 20% dimethylformamide solution at 130°C.
■Time lights cluster. At the end of the reaction, the reaction was carried out by thin layer chromatography [thin layer plate: same as Example 1]. Developing solvent; benzene:ether (9:1)]
After confirmation, the reaction solution was concentrated under reduced pressure, extracted with chloroform, washed with 1% sodium thiosulfate and water, and dried over anhydrous sodium sulfate. The crystals obtained by treating the chloroform layer were washed with methanol and then recrystallized from chloroform-methanol to obtain the desired product (yield: 53%).
I got it. Melting point 238-90, [a]o; +180 (C
= 1, chloroform) Elemental analysis value Actual value as 27091 C: 57.81H: 3.84 Calculated value C: 57.81H: 3.84 N, M, R, spectrum 6 6.131 days d J, , 2 8HZ H-15.
881 days d, d J2,3 11HZ H-24.60
1 day t J3,4 11HZ H-35.791 day m
J4,5 11HZ H-4 Example 33-deoxy-3-iodo-D-glucose synthesis a 3101 (
P-toluenesulfonyl-D-glucose 2.0 m (8
hm. 1) Add a solution of 2.7 lahmol of sodium iodide and 20 mol of dimethylformamide to 120q0 for 4 hours. At the end of the reaction, the reaction was analyzed by thin layer chromatography [thin layer plate: same as in Example 1, developing solvent: chloroform:methanol (7:3
)], the reaction solution is concentrated under reduced pressure. Dissolve the concentrated residue in water and apply it to Amberlite IR-20 (Niju)
200' and Diaion WA-20 (freebase)
After desalting on 200 ml of water and concentrating under reduced pressure, the product was crystallized from ethanol to obtain 0.78 g of the desired product (yield: 45%). Melting point: 141-2o, [a]o=+51o (C=2, water) The properties of the acetylated compound were the same as those obtained in Example 1. b) 1,2,4,6-tetra-○-acetyl-3-deoxy-3-iodo-8-D-glucopyranose (4.37 mmol) was dissolved in 30 mmol of IN-hydrochloric acid,
Concentrate at 100°C for 30 minutes.

Claims (1)

[Claims] 1 General formula [I] ▲ Numerical formula, chemical formula, table, etc.▼ (However, in the formula, R_1 represents an alkylsulfonyl or arylsulfonyl group, and R_2 represents a hydrogen atom or an acyl group.) 3-deoxy- represented by the general formula [II] (wherein R_2 has the same meaning as above), which is characterized by reacting a glucose derivative obtained by reacting with an alkali metal iodide in an aprotic polar solvent. 3-iodo-D-
Method for producing glucose derivative. ▲Contains mathematical formulas, chemical formulas, tables, etc.▼