JPH0148892B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel isethionate ester represented by the following formula [] or [], for example, a compound having a hydroxyl group, a carboxyl group, a mercabuto group, an amino group, or a compound having a purine, pyrimidine, etc. Effective as an alkylating agent that adds alkyl groups to heterocyclic compounds, as well as proteins and nucleic acids, especially in aqueous media by taking advantage of its water solubility, and effective against mouse sarcoma, mouse adenocarcinoma, mouse leukemia, etc. The present invention provides a novel compound that is useful as an anticancer agent, an antiviral agent, and the like.

In the above formula [], R is a methyl group, n-propyl group or i-propyl group, and R' in the above formula [] is an alkylene group having 2 to 5 carbon atoms, such as an ethylene group, a propylene group, a 1,4 -butylene group, 1,5-amylene group.

Specifically, the compound of formula [] is methyl isethionate, n-propyl isethionate, and i-propyl isethionate.

Specific examples of the compound of formula [] include ethylene glycol isethionate, propylene glycol diisethionate, 1,4-butanediol isethionate, 1,5-pentanediol diisethionate, etc. can give.

The isethionate ester of the present invention is, for example, the following two
It can be manufactured in the same way.

It can be produced by reacting a silver salt of isethionic acid with an alkyl halide in an organic solvent. In this reaction, the theoretical reaction amount of alkyl halide per mole of silver isethionate is:
When the target product is isethionate ester of formula [], it is 1 mole, and when the target product is isethionate ester of formula [], it is 1/2 mole,
In the actual reaction, it is preferable to carry out the reaction using these theoretical amounts, but the amount is not necessarily limited to this, and there may be some excess or deficiency.

The reactivity of alkyl halides decreases in the order of iodide, bromide, and chloride, and in the case of chloride, it is necessary to lengthen the reaction time or raise the reaction temperature.

When producing isethionic acid ester of the above formula [], the alkyl halide may be, for example, alkyl iodide such as methyl iodide or i-propyl iodide, alkyl chloride or methyl bromide such as methyl chloride or i-propyl chloride, or methyl bromide. Monohalogenated alkyl represented by alkyl bromide such as i-propyl compound is used, and when producing isethionate ester of formula [], halogenated alkyl such as 1,2-dichloroethane, 1,
Dichloroalkyl such as 2-dichloropropane, 1,4-dichlorobutane, or 1,2-dibromoethane, 1,2-dibromopropane, 1,4
- Dihalogenated alkyl represented by dibromoalkyl such as dibromobutane is used.

The reaction is generally carried out in an organic solvent such as methanol,
This is carried out using alcohols such as ethanol or acetonitrile, but no catalyst is particularly required. The amount of solvent to be used may be in accordance with a conventional method carried out in the desilver halide reaction between a silver salt of an organic acid and an alkyl halide, and is approximately several tens of times the amount of the alkyl halide.

The reaction temperature may be either room temperature or heating, but heating is preferable from the viewpoint of reaction rate. If the temperature is too high, the yield will decrease, so a temperature of 60°C or lower is suitable.

The required reaction time varies somewhat depending on the type of reaction raw materials and reaction temperature, but is about 24 to 48 hours at room temperature, and about 10 hours at 45 to 60°C, for example.

After the reaction, the precipitated silver halide is removed by suitable means, and the solution is subjected to distillation, for example, to remove the solvent, thereby obtaining the desired product. It is also preferable to use a column filled with silica gel or the like as a separation means.

It may also be produced by reacting isethionyl chloride with the corresponding alcohol in an organic solvent.

The only existing example of this production method is a report on the production of butyl isethionate. However, a drawback of this method is that isethionic acid chloride, for example, is extremely unstable and is only stable at -20°C.

Since the isethionate ester of the present invention has a strong alkylating ability, it is suitably used as an alkylating agent for introducing an alkyl group into various organic compounds. For example, it is suitable for alkylating oxygen atoms in alcohols, phenols, etc., and alkylating nitrogen atoms in various amines, etc.

Furthermore, when administered to humans or animals, it has anticancer, antiviral, and antibacterial effects, and has low toxicity, making it useful as an anticancer, antiviral, and antibacterial agent.

Next, the present invention will be explained in more detail with reference to Examples.

In each example, infrared absorption spectrum analysis was performed using a chloroform solution using a NaCl cell.

Example 1 2.5 g of silver isethionate and 2.3 g of methyl iodide were dissolved in 30 ml of acetonitrile and left at room temperature for 8 hours.

After filtering the precipitated silver iodide and concentrating the liquid, the remaining liquid was distilled under reduced pressure to 80~95℃~2mmHg.
Isethionic acid methyl ester was obtained as a fraction.

What was obtained was a colorless liquid soluble in water, with a yield of 80%.

Regarding this, nuclear magnetic resonance spectroscopy (hereinafter referred to as
NMR analysis), infrared absorption spectrum analysis (hereinafter referred to as IR analysis), and elemental analysis were performed.

NMR analysis (see Figure 1): 3.23ppm (1H, singlet) 3.38ppm (2H, triplet, J=5H ₂ ) 3.94ppm (3H, singlet) 4.06ppm (2H, triplet, J=5H ₂ ) IR analysis (see Figure 2): 980CM ^-1 (S-O-C
Stretching) 1155CM ^-1 (S(=O) ₂ symmetrical stretching) 1355CM ^-1 (S(=O) ₂ asymmetrical stretching) 3550CM ^-1 (O-H stretching) Elemental analysis (C ₃ H ₈ O ₄ S): Estimation Value H5.75%, C25.71% Measured value H6.01%, C25.96% Example 2 Silver isethionate 2.5g, isopropyl iodide 5
g was dissolved in 20 ml of acetonitrile and left at room temperature for 20 hours. After filtering the precipitated silver iodide and distilling off the liquid, the desired product is extracted from the remaining liquid using 50g of silica gel.
The mixture was separated and purified using a column packed with chloroform and eluted with chloroform to obtain isethionic acid isothionate isopropyl ester, which is a colorless liquid soluble in water. The yield was 85%. NMR, IR and elemental analysis were performed on this.

NMR analysis (see Figure 3): 1.44ppm (6H, doublet, J=7H ₂ ) 2.65ppm (1H, singlet) 3.35ppm (2H, triplet, J=5H ₂ ) 4.08ppm (2H, triplet line, J=5H ₂ ) 5.01ppm (1H, septet, J=7H ₂ ) IR analysis (see Figure 4): 910CM ^-1 (S-C-C
Stretching) 1159CM ^-1 (S(=O) ₂ symmetrical stretching) 1332CM ^-1 (S(=O) ₂ asymmetrical stretching) 3550CM ^-1 (O-H stretching) Elemental analysis (C ₅ H ₁₂ O ₄ S): Estimation Value H7.19%, C35.70% Actual value H7.46%, C35.26% Example 3 5.0 g of silver isethionate and 2 g of 1,4-dibromobutane were dissolved in 17 ml of acetonitrile and heated to 19
Warmed for hours.

The precipitated silver bromide was filtered off, and the solution was concentrated.

The desired product was separated and purified from the remaining liquid using a column packed with 75 g of silica gel and eluted with 5% methanol-chloroform to obtain 1,4-butanediol diisethionate, which is a colorless liquid soluble in water. The yield was 70%. about this
NMR, IR and elemental analysis were performed.

NMR analysis (see Figure 5): 1.89ppm (4H, broad singlet) 3.41ppm (4H, triplet, J=6H ₂ ) 4.01ppm (4H, triplet, J=6H ₂ ) 4.07ppm (2H, singlet line) 4.31ppm (4H, broad singlet) IR analysis (see Figure 6): 940CM ^-1 (S-O-C stretching) 1159CM ^-1 (S(=O) ₂ symmetrical stretching) 1357CM ^-1 (S( =O) ₂ asymmetric expansion and contraction) 3552CM ^-1 (O-H expansion and contraction) Elemental analysis (C ₈ H ₁₈ O ₈ S ₂ ): Estimated value H5.92%, C31.37% Measured value H5.73%, C31.12 % Example 4 2.8 g of silver isethionate and 1.8 g of 1,5-diiodopentane were dissolved in 40 ml of acetonitrile and heated at 37°C.
It was heated for 18 hours.

The precipitated silver iodide was filtered off, and the solution was concentrated.

The target product is separated and purified from the remaining liquid using a column packed with 100 g of silica gel and eluted with 5% methanol-chloroform to obtain 1,5, which is a water-soluble liquid.
-Pentanediol diisethionate ester was obtained.

The yield was 75%. Regarding this, NMR, IR
and elemental analysis.

NMR analysis (see Figure 7): 1.70ppm (6H, multiplet) 3.38ppm (4H, triplet, J=6H ₂ ) 3.63ppm (2H, singlet) 4.04ppm (4H, triplet, J=6H ₂ ) 4.30ppm (4H, triple line, J=6H ₂ ) IR analysis (see Figure 8): 943CM ^-1 (S-O-C stretching) 1159CM ^-1 (S(=O) ₂ symmetrical stretching) 1350CM ^-1 (S(=O) ₂ asymmetric expansion and contraction) 3550CM ^-1 (O-H expansion and contraction) Elemental analysis (C ₉ H ₂₀ O ₈ S ₂ ): Estimated value H6.29%, C33.74% Measured value H6.45%, C33.64%

[Brief explanation of drawings]

Fig. 1 is a nuclear magnetic resonance spectrum diagram of isethionic acid methyl ester obtained in Example 1, Fig. 2 is its infrared absorption spectrum diagram, and Fig. 3 is a diagram of Example 2.
Figure 4 is the infrared absorption spectrum of isethionate isopropyl ester obtained in Example 3. Figure 5 is the nuclear magnetic resonance spectrum of 1,4-butanediol diisethionate obtained in Example 3. Resonance spectrum diagram, Figure 6 is its infrared absorption spectrum diagram, Figure 7 is its nuclear magnetic resonance spectrum diagram of 1,5-pentanediol isethionate obtained in Example 4, and Figure 8 is its infrared absorption spectrum diagram. It is a diagram.

Claims (1)

[Claims] 1. Isethionate ester represented by the following general formula [] or []. HOCH ₂ CH ₂ SO ₃ ―R ...[] However, R is a methyl group, n-propyl group, or i-
It is a propyl group. However, R' is an alkylene group having 2 to 5 carbon atoms.