DE2533899C3 - Process for the preparation of steryl-β-glucoside esters - Google Patents

Description

HIGH ₂

HO

(III) with a sulfonyl chloride compound of _{the general formula R 2 -SO 2} Cl and the resulting steryl-6-O-sulfonyl- ^ D-glucoside of the general formula (II)

R ₂ SO ₂ OCH ₂

HO

OH

OH

reacts with an alkali salt of palmitic acid, where in the above formulas (I), (II) and (III) Ri the 0-sitosteryl, campesteryl, stigmasteryl or a cholesteryl group or a mixture thereof and R2 is an alkyl, aryl or substituted one Is aryl group.

The invention relates to a process for the preparation of 35 or cholesteryl group or a mixture thereof. of steryl-6-O-palmitoyl-0-D-glucoside of the general The invention provides a method of manufacture

Formula ~ - -

CH ₁ (CHj) ₁₄ COOCH

HO

(D

in the ri the 0-sitosteryl, campesteryl, stigmasteryl of steryl-6-O-palmitoyl-j3-D-glycoside (1) by reaction of, for example, steryl-0-D-glucoside (II), which consists of Lecithin or the 0-D-glucoside of commercially available j3-sitosterol, which has a purity of about 60% and additionally contains campesterine, stigmasterine and the like, is available, with sulfonyl chlorides, after which the obtained steryl-6-O-sulfonyl-j3-D-glucoside (II) with an alkali salt, for example the sodium or potassium salt, which reacts with palmitic acid. This Reactions can be expressed by the following formulas:

HIGH

R ₂ SO ₂ OCH ₂

HO

CH ₃ (CH ₂ ) ₁₄ COOCB

? ^Rl CH ₃ (CH ₂ J ₁₄ COOZ

(III)

(II)

HO

(D

In the above formulas, Z is an alkali metal, Ri is the ß-sitosteryl, campesteryl, stigmasteryl or Cholesteryl group or a mixture thereof and R2 is one Alkyl, aryl or substituted aryl group.

The compounds (I) obtained according to the invention have a strong anti-inflammatory effect extremely low toxicity and are extremely useful drugs. The values for the acute The toxicity and the inhibitory effect of carrageenin edema of the compound (I) are as follows Tables 1 and 2 respectively.

Table 1 Acute toxicity (LD ₅₀ ) in mice

Inlraperitoneal injection Oral administration (male) (female) (male) (female)

> 3000

> 3000

> 3000

> 3000

Table 2 Inhibition effect of carrageenin edema

(Paw edema method in rats)

Dose (mg / kg) inhibition (%)

(Lp.) Lh 2h 3h 4h 5h

-3.7
24.2

13.2 37.6

26.6 41.6

42.8

24.9 28.1

"5

.1 °

When carrying out the process according to the invention, it is advantageous to use steryl-0-D-glucoside (III) in To dissolve pyridine and to let it react with a sulfonyl chloride compound with cooling, whereby Steryl-6-O-sulfonyl - /? - D-glucoside (II) is obtained, which then preferably with sodium or Kaliutnpalmitat in a suitable solvent, such as for example Ν, Ν-dimethylformamide, ethanol or dioxane, is reacted with heating.

The invention is explained in detail below with the aid of examples, which, however, do not imply any restriction of the scope of the invention.

example 1 [Production of (II) from (UI)]

23 g of steryl-ß-D-glucoside (III) were dissolved in 100 ml of pyridine and admixed with 23 g of p-toluenesulfonyl chloride while cooling with ice. The reaction mixture was _allowed to slowly reach room temperature. The reaction mixture was stirred for about three hours, after which the reaction was stopped by adding a small amount of methanol. The solvent was distilled off under reduced pressure and the residue was recrystallized from ethanol. 15 g of steryl-6-Op-ToluoIsul-

45 fonyl-0-D-glucoside (II) with a melting point of 156 bis 157 ° C obtained.

Elemental analysis for 042H ₆₆ O ₈ S · 1/2 H ₂ O: Calculated: C 68.16, H 9.13, S 4.33%; Found: C 68.15, H 9.36, S 4.23%.

According to another embodiment, the steryl - /? - D-glucoside (III) can also be mixed with other sulfonyl chloride compounds in the manner described above implemented. Examples of such sulfonyl chloride compounds are p-chlorobenzenesulfonyl chloride, 23,5,6-tetramethylbenzenesulfonyl chloride, 23,4,5,6-pentamethylbenzenesulfonyl chloride, 2,4,6-trimethylbenzenesulfonyl chloride, 2-methylbenzenesulfonyl chloride, 2-nitrobenzenesulfonyl chloride, benzenesulfonyl chloride and methanesulfonyl chloride.

The reaction according to Example 1 was followed by thin layer chromatography, and the product (II) was isolated from the reaction mixture when it gave the largest spot. The yields obtained were nearly equal to those as determined by colorimetric methods on the basis of sterols developed dyes were obtained. The yield of this example using p-toluenesulfonyl chloride was 50 to 60%, while that by Using the other sulfonyl chlorides listed above, yields obtained at 50 to 65% lay.

Example 2

[Preparation of (1) from (H)]

1 g of the 6-Op-toluenesulfonyl derivative (II) of the compound (III) was dissolved in 20 ml of Ν, Ν-dimethylformamide and then treated with 0.57 g of powdered sodium palmitate, after which the mixture was ^{heated to 120 °} C. for 13 hours while stirring would. The mixture slowly developed its color. After the completion of the reaction, chloroform was added and the insolubles were filtered off. The filtrate was treated with activated charcoal and distilled in vacuo, whereby 840 mg of crude crystals of (I) were obtained. The crystals were recrystallized from ethanol, whereby the pure product with the melting point 120 to 190 ^° C. was obtained. Elemental analysis for C51H90O7:

Calculated: C 75.13, H 11.13%;

found: C 74.89, H 10.90%.

Claims (1)

Claim: Process for the production of steryl-6-O-palmitoyl - /? - D-glucoside the general formula CH ₃ (CH ₂ ^ COOCH (D characterized in that one steryl - /; - D-glucoside of the general formula