DD143765A5 - PROCESS FOR THE PREPARATION OF NEW XYLITE DERIVATIVES - Google Patents

Description

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Process for the preparation of new XTLIT-I) ERIVATM Field of application of the invention:

Pie invention "relates to a process for the preparation of new xylitol derivatives of the general formula

CH ₂ -R ¹

CH-R (I)

R ⁵ -O-CH ι

CH-R ⁴ t

CH ₂ -R ⁵ wherein

R and R represent the same substituents and signify halogen, tosyloxy or mesyloxy, in which case

2 4

R and R are hydroxyl or

R and R and R and R 'together form an oxygen bridge

and · -

K independently of the meaning of R, R, R, R ^ for

Hydrogen, alkanoyl or aralkanoyl aroyl is _e

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Characteristic of the known technical solutions;

It is known that certain sugar-alo-alcoholic compounds containing 4 or 6 carbon atoms possess cytostatic properties (Keoplasma, IJ, I5 / 1970 /). These compounds are dihalogenated.

or dimesyloxy derivatives due to terites and hexites, or diepoxy derivatives thereof. These compounds are characterized by the same property, the hydroxyl groups of which are free, ie not blocked with acetal groups (Drugs Residue / 1 £, 668-70. / 1964 / and Tetrahedron Letters, 20, 716, / 1961 /). ,

Explanation of the Ifesens of the invention;

It has been found that the novel sytostatic compounds of the general formula I can be prepared so that the xylitol of the general formula

CH ₉ -OH '(II)

CH-OH t

HO-CH 1

CH-OH ι

CH ₂ -OH

first optionally in the presence of acid-binding agents with

Acylated acylating agent of the general formula R-R and then the compounds of the general formula

SH ₉ -R ¹ (III)

CH-OH 1

HIGH · · -

CH ₉ -R

-j- 21

those included within the scope of the compounds of general formula I are, if desired, treated with a basic acid-binding agent and thus dianhydro-xylitol of the general formula

CH ₂ -R ¹ '(IV)

CH-OH ι

R-O-CH ι

CH-OH CH ₂ -R ⁵

which is optionally acylated with an acylating agent of the general formula R -X or (R) ₉ 0 and 3-acyl derivatives of the general formula

^ O (V)

CH

R ⁸ -0-CH

CH

-Dianhydro-xylitol of the general formula IV or 3-acyl derivative of the general formula V is acylated with an acylating agent of the general formula R-R to give compounds of the general formula III or

CH ₉ -R ° (Vl)

, CH-OH j

R ⁸ -O-CH ι

CH-OH CH ₂ -R ⁶

The compounds which can be characterized by the general formulas III, IV, V and VI belong to all of the compounds

of the general formula I and form a special group of the same »j

Xylites of the general formula II can be reacted with an acylating agent of the general formula U-R by several methods. If the acylating agent used is a hydrohalic acid, the xylitol can be heated with a concentrated aqueous solution of the hydrohalic acid, if appropriate under pressure.

If, as the acylating agent of the general formula R-R, mesyl or tosyl halides are used, then the binding of the halo-hydrogen acid which arises during the reaction must be carried out by using an acid-binding agent the usual, and often used in organic chemistry acid binding agents there are suitable ₀ Examples of acid-binding agents are tertiary amines * Z ₀ as pyridine, trialkylamines, or alkali Pikolinoj metal and alkaline earth metal carbonates and Wasserstof f ~ carbonates or phosphates, Those acid binders are preferably used which are easily removed from the reaction mixture during the acid-binding of a salt thereof. "

The compounds obtained during the first stage of the general. ; Formula III itself are used as eytostatic agents and can also be converted into other xylitol derivatives according to the invention. "If z» B »the compounds of general formula III are treated with a basic acid binder, dianhydro- xylitol of the general formula is formed IV.

In this reaction, any strong organic or inorganic base may be suitable as the basic acid binder.

"2?

It is possible to use, for example, alkali metal or alkaline earth metal alcoholates or organic nitrogen bases and, as inorganic bases, alkali metal hydroxides, carbonates or hydrogencarbonates. The reaction can also be carried out with anion _or exchangers in hydroxyl

- 5 - 212 7

Form be performed.

Dianhydro-xylitol dor formula IV, which was prepared by the above reaction, can be further reacted by two methods. According to the first process variant, the reaction leading to the compound of the formula IV is reversed by reacting dianhydroxylitol of the formula IV with a preferably not the one used in the first stage.

6? - Reacted acylating agent of the general formula R-R under the reaction conditions given in the first stage. In the case of using hydrogen halide as the acylating agent, the reaction may be carried out under milder reaction conditions by dissolving dianhydro-xilitol of the formula IV in a concentrated aqueous solution of an alkyl salt of hydrohalic acid, followed by stirring a concentrated solution of a strong acid, eg Sulfuric acid or perchloric acid at such a rate to the solution that the pH of the reaction mixture at · * becomes nearly neutral (pH = 6.5-7). The product of the reaction is a compound of the same general formula as the product of the first stage - that is of the formula III - but wherein R 1 is preferably different groups than in the product of the first stage. By the latter reaction, it is also possible to prepare those compounds of the general formula which could not be prepared in good yield after the first reaction stage,

The second method for further reaction of the anhydro-xylitol Formal IV consists of the reaction of the dianhydro-xylitol in the presence of an acid binder with an acylating agent of the general formal

QQ Q

R "» X or (R) pO - wherein R is alkanoyl, aralkanoyl or aroyl and X is halogen. The product of the reaction is a 3-A.cyl-derivative

vat the general formula V - wherein R is as indicated above. As the acid-binding agent of the reaction, it is possible to use any acid binder customary in organic chemistry. The at the first

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Acid binders enumerated in the reaction step are preferred. However, when acetic anhydride is used as the acylating agent, it is possible to bind the resulting acid with an alkali metal acetate. The acid binder has to shift the equilibrium of the reaction in the direction of the acylated product by binding the acid formed during the reaction, so it is critical which acid binder is chosen.

In the tjbar examination of Dir.nhydro-xylitol of the general formula IV in the compounds of general formula III under indicated Um-. Also, the obtained 3-acyl derivatives of the general

Acylating agents of general formula R-R are acylated to give compounds of general formula VI ## STR5 ## The acid binders used here and acylating agents are as indicated above,

The formula sheet illustrates the reactions by which the various types of compounds of general formula I are prepared from xylitol of general formula II. The characteristic reagents are also indicated

1 5

In the definition of R and R, halogen can mean any halogen.

R 1 and R 4 are preferably chlorine, bromine or iodine, particularly preferably bromine.

Under tosyloxy and mesyloxy x'ersteht you various toluenesulfonyloxy groups, especially p-toluenesulfonyloxy groups, or methylsulfonyloxy Gruppa.

Alkanoyl Groups in the meaning of R contain 1-10 carbon atoms, preferably 1-6 carbon atoms and may be straight or branched and optionally substituted by one or more halogen. It

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is particularly preferred when R ^ alkanoyl group contains 1-4 carbon atoms and is acetyl. The alkyl portion of the aralkanoyl groups R contains 1-10 carbon atoms, preferably 1-6 carbon atoms. The carbon chain of the alkyl moiety may be straight or branched, and any carbon atom of the chain may be substituted by an optionally substituted, preferably unsubstituted aryl of 6-10 carbon atoms, preferably phenyl. One of the preferred representatives of the aralkanoyl groups is

3 ·

-Phenylbutyryl group t Aroyl groups instead of R are substituted or unsubstituted. Me aromatic groups may advantageously contain 6-10 carbon atoms and as substituents similar to the Arylteil dor Aralkanoylgruppen carry one or more halogen, nitro, Trifluorniethyl, alkyl, phenyl, amino or sulfonyl. One dar

3 preferred representatives of aroyl groups. R is p-phenylbenzoyl.

6 7

Halogen atoms instead of X, R or R may be chlorine, bromine or led, preferably chlorine.

The pharmacological activity of the compounds of general formula I according to the invention is demonstrated by the example of 3- (p-phenylbenzoyl) -1,2-4,5-dianhydro-xylits and 1,2-4,5-dianhydro-xylits ,

a) NK / Ly ascites tumor in mice

The mice were transplanted with 10 'cell number and on the first day at a dose of 600 mg / kg, 300 rag / kg and 150 mg / kg intraperitoneally. treated with 3- (p-phenylbenzoyl) -1,2-4,5-dianhydro-xylitol. The untreated animals died 17 to 23 days after transplantation. In the treated animals, on the 50th day after transplantation, 70, 60 or 30 % of the animals were still alive (the order follows the order of dosing).

When the animals were intraperitoneally treated at the dose of 700 and 500 mg / kg, respectively, on the 3rd day after the transplantation, on the 40th day after

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the transplant 100 or 60 % of the animals alive.

b) L 1210 leukemia in mice

DBA / 2 strain mice were transplanted intraperitoneally with 10 ⁵ cell number. The animals were treated intraperitoneally with 3- (p-phenylbenzoyl) -1,2-4,5-dianhydro-xylitol at 1, 4 and 7 days after transplantation at a dose of 200 to 400 mg / kg. The untreated animals died between the 9th and 11th days after transplantation. The treated animals only died on the 13th day,

c) S 18O Solid Tumor in Mice

Mice from the CFLP strain were transplanted subcutaneously with tumor. On the 1st, 4th and 10th day after the transplant, the animals were dosed at 400 bw. 500 mg / kg intraperitoneally with 3- (p-phenylbenzoyi) -1,2-4,5-dianhydro-xylitol. The average survival time of untreated animals is 23 days, whereas that of treated animals is 33 days.

d) Yoshida solid sarcoma in rats .

Rats from the CYF strain were subcutaneously treated with the test tumor in a cell count of 7 × 10 -3. The animals were injected intraperitoneally at 3 × 10 5 and 12 days after transplantation at a dose of 200 rag / kg - (p-Phenylbenzoyl) -1,2-4,5-dianhydro-xylit treated. The size of the tumor was 55 % smaller compared to the control. Fifty percent of control animals died on the 20th day after transplant when 80 % of the treated animals were still alive. 20 % of the treated animals were still alive on the 25th day after the control animals were used.

e) NK / Ly ascites Tu mor on mice

The examination was carried out as indicated under a), with the difference that the test compound was 1,2-4,5-dianhydroxylitol, which was administered at a dose of 20 mg / kg. 60 % of the experimental animals were still alive on the 60th day after transplantation »

£) Toxic quotes experiment

The intraperitoneal LD ₁ -Q dose in mice was 1000 mg / kg in the case of 3- (p-phosphorylbenzoyl) -1j 2 -4,5 dianhydroxylitol, in the case of 1,2-4,5-dianhydro-

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xylitol 200 mg / kg LD_ dose of the latter compound is 160 mg / kg.

As can be seen from the data of the animal experiments, the novel compounds of the general formula I according to the invention have valuable cytostatic properties and can thus be used as an active ingredient in cytostatic pharmaceutical preparations. These pharmaceutical preparations contain, in addition to the active ingredients (or other than the active ingredient), excipients, diluents, stabilizers, taste-improving agents and / or formulation auxiliaries. The pharmaceutical preparations e.g. Tablets, but can also be tabletted without inert additives.

In the preparation of the pharmaceutical preparations are advantageously non-toxic; solid, liquid, semi-liquid or pressure-liquefied gaseous additives used. The active ingredients are formulated by using the excipients in the form of tablets, dragees, granules, powders, capsulated powders, ointments, creams, solutions or spray. The solutions include various preparations suitable for injection, infusion, peroral or topical administration. The active compounds of the general formula I can also be formulated in the form of crystal ampoules. If necessary - especially with injection and infusion preparations are still the pH value or the osmosis pressure of the solution to be administered influencing or stabilizing additives. Various buffers and sodium chloride salt are used for this purpose.

The active compounds according to the invention are administered for 1-10 days at a dose of 1-30 mg / kg / day, preferably in several individual dosage units, the dose depending on the disease's disease to be treated and on the individual tolerance of the patient.

The treatment can be carried out with the pharmaceutical preparations containing the active substance according to the invention, but it is possible to use diQ

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also combine with the use of pharmaceutical preparations containing a plurality of different active substances and thus form a modern treatment system,

EXAMPLES

Further details of the invention are illustrated by the following examples without limiting the invention to the examples.

1.0 kg of xylitol is dissolved with 2000 ml of 65% strength concentrated hydrobromic acid unc. the solution is saturated with hydrogen bromide gas at 0 C and in a closed system for 4 hours at 85 C genanten. After cooling, sodium carbonate is added to the reaction mixture with stirring until pH = 6, after which the precipitated amount of crystals is filtered and uracilcrystallized from ethyl acetate. 1390 g of 1,5-dibromo-1,5-dideoxy-

Melting point: 104-106 ⁰ C, yield: 76.5% R _f = 0.85 (62: 62: 30: 23:

20 mixture of benzene: methanol: n-amyl alcohol: water: isopropanol),

Beisgiel_2

1600 ml of Varion AD ion exchange resin in the hydroxylforra (strong basic amino group-containing polystyrene resin manufactured by Nitrokeraia Ipartelepek, Balatonfüzfö, Hungary), 222.4 g of 1,5-dibromo-1,5-dideoxy-xylitol and 1600 ml of distilled water, Stirred for 15 minutes. The ion exchange resin is removed by filtration and washed with distilled water. The aqueous solutions are concentrated under reduced pressure to 1 liter and the residue is added with stirring to a suspension prepared from 20 liters of ethyl acetate and 2 kg of sodium carbonate. From the ethyl acetate phase, the water is removed and the mixture is concentrated to dryness. The crude product is chromatographed on silica gel. 54 g of pure 1,2-4,5-dianhydroxylyl are obtained. Xylitol epoxidge-

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Hold: 98-IOO J6, R _f = 0.05 (95: 5 benzene-ethyl acetate).

Beisgiel_3

2 g of 1,2-4,5-dianhydro-xylitol are dissolved in 2 ml of distilled water and the solution is added dropwise with stirring in 12 ml of concentrated hydrobromic acid. After 10 minutes, add so much sodium carbonate in the solution until the pH reaches 6, the precipitated crude product is filtered and uracilcrystallized from ethyl acetate. This gives 3 »5 g of 1,5-dibromo-1,5-dideoxy-xylitol. Melting point: 104- 106 ⁰ C.

Example 4

2 g of 1,2-4 ·, 5-dianhydro-xylitol are dissolved in 2 ml of distilled water and the solution is added dropwise with cooling in 15 ml of concentrated hydrogen iodide solution. After 10 minutes, the solution is cooled to ⁰ ° C., the precipitated crude product is filtered and crystallized from ethyl acetate. This gives 3 »1 g of 1,5-diiodo-1,5-dideoxy-xylitol. Melting point: 115-118 ⁰ C, R. = 0.865 (solvent as in Example 1),

example ^

2 g of 1,2-4,5-dianhydro-xylitol are dissolved in 2 ml of distilled water and the solution is added dropwise with cooling in 10 ml of concentrated hydrochloric acid solution. After 10 minutes, the solution is concentrated to dryness in vacuo. The residue is dissolved in 50 ml of ethyl acetate and extracted by shaking with saturated, aqueous sodium bicarbonate solution. The ethyl acetate phase is dried and concentrated in vacuo. This gives 1.4 g of colorless 1,5-dichloro-i, 5-dideoxy-xylitol. R "s 0.855 (eluent as indicated in Example 1).

Example 6

12 g of crude 1,2-4,5-dianhydro-xylitol (purity about 75%) were dissolved in 250 ml of anhydrous benzene and 14 ml of anhydrous are added with stirring

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Triäthylamin and with stirring within 3 hours at 45 ⁰ C to 21.6 gp ~ phenylbenzoyl chloride, after which the precipitated product is filtered and washed with benzene. The benzene solutions are concentrated in vacuo. The syrup residue is chromatographed on silica gel with a benzene-ethyl acetate mixture. The 3-p (phenylbenzoyl) -1,2-4,5-dianhydro-xylitol containing fractions are concentrated in vacuo. The residue is recrystallized from ethanol. This gives 12.5 g of pure product. '

Melting point: 86-88 ⁰ C, R _f = 0.344 (solvent as in example 2).

Example_7

1 »16 g of 1,2-4,5-dianhydro-xylitol is dissolved in 25 ml of anhydrous benzene and added dropwise to the solution with stirring 1.4 ml of anhydrous tri-'thylamine at 45 ⁰ C and 1.82 g $ *" The mixture is stirred for 30 minutes and the precipitated product is filtered and washed with benzene, the combined benzene solutions are concentrated in vacuo, the syrup residue is chromatographed on silica gel with benzene-ethyl acetate mixture * '- phenylbutyryl) -1,2-4,5 ~ dianhydro-xylitol-containing fractions are concentrated to dryness to give 1.4 g of colorless oil E _f = s 0.30 (eluent as in Example 2).

Beisgiel_8

1 »16 g of 1,2-4,5-dianhydro-xylitol are dissolved in 25 ml of anhydrous benzene and 1.4 ml of anhydrous benzene are added to the solution. At 45 C is added dropwise to a solution of 0.71 g of anhydrous acetyl chloride in 3 ml of anhydrous benzene in one hour. The solution is stirred for 30 minutes at 45 C and the mixture is worked up further in Example 7. The product is crystallized from ethyl acetate. This gives 0.88 g of S-acetyl-i ^^^ dianhydro-xylitol. ,

Melting point: 36-38 ⁰ C. R _f = 0.25 (eluent as in Example 2).

212 7 8 0

Beisgiel_9,

0.5 g of 3- (p-phenylbenzoyl) -1,2-4,5-dianhydro-xylitol is dissolved in 1 ml of acetone and the solution is cooled to OC. The solution is added dropwise in 5 ml of concentrated hydrogen bromide solution cooled below 0 ° C. After 30 minutes, the mixture is diluted with 10 ml of water and allowed to stand at 0 ^° C. for 8-12 hours. The reaction mixture is filtered and the amount of crystals is washed to neutral and the product recrystallized from benzene. This gives 0.3 g of 3- (p-Ph® ' ^{: 1-} ylbenzoyl) -1,5-dibromo-1,5-dideoxy xylitol.

Melting point: 122-125 ⁰ C. R _f = 0.32 (eluant as described in Example 2).

Beisgiel 10

3 g of 1,2-4,5-dianhydro-xylitol are dissolved in 75 ml of anhydrous benzene. 4.2 ml of anhydrous triethylamine are added dropwise, and at 45 ^° C. a solution of 3 ml of benzoyl chloride in 5 ml of anhydrous benzene is added. The mixture is stirred for 3 ° 45 minutes at ⁰ C. The mixture is worked up according to Example 8, for recrystallization is used a mixture of hexane and ethyl acetate. 3-Banzoyl-1,2-4,5-dihydroxylitol is obtained. ,

Yield: 2.8 g. Melting point: 39-40 ⁰ C, R _f = 0.28 (eluent as in Example 2).

The thin-layer chromatographic experiments were in each case carried out on "DC precast silica gel" plates of size 20 × 20 cm (Merck). The 1.2-4.5-dianhydro derivatives were treated with a 5 follow methanolic nitrobenzyl-pyridine and then induced by heating, and the 1 "5-dihalo-1,5 ~ dideoxy-derivatives have been caused by the fact that the nitrobenzyl Pyridine solution sprayed plates after heating also sprayed with a 50 's methanolisehea Triäthylaminlösung sprayed.

. * - 2127

Kristal ampoule!

Active ingredient of particle size 0.06-0.32 mm was filled under aseptic conditions with a dosing, in Kristallampul1en. They are packed together with a 10 ml iso.tonic broth vial »

Beis £ iel_i2

2500 mg of crystalline active ingredient, 450 g of anhydrous lactose and 1 mg of anhydrous cellulose are kneaded into a homogenizer with a mixture of 80 g of paraffin oil and 350 ml of isopropanol. The mass is granulated and dried. To the dry substance is added 50 g of talc, the mixture is homogenized and pressed into 325 rag tablets. One tablet contains 250 mg active substance.

Example_13.

1000 μg of crystalline active ingredient are homogenized with a previously thoroughly mixed mixture of 50 g of Carbowax 6OOO and 50 g of talcum. The resulting powder mixture is filled with a filling machine at a setting of 110 mg hard gelatin capsules.

Entorosolvens tablets and capsules

The preparations prepared according to Examples 12 or 13 are provided with a known intestinosolventic coating.

CH 1 R-OC H

CH

R ²

CH-OH HO-CH

CH-OH C H-OH

CH _r OH CH-OH

HO-CH I CH-OH

R ⁶ -R ⁷

CH ₂ -OH ti · CHx-R " ¹

CH-OH

HO-CH i CH-OH

I -

r R ⁵

CH _Z R ⁶ -O-CH

CH-OH

CH-OH CH-R ⁶

Vi.

Claims (12)

Invention claim: 1φ Process for the preparation of novel .Xylit derivatives of the general formula I ₂ CH-R I R ^ -O-CH CH-R ⁴ CH ₂ -R ⁵ wherein R and R are the same and are halogen, tosyloxy or mesyloxy, in which case 4 R and R are hydroxyl or OA R K and R and R and R together form an oxygen bridge, 12 4 R independently of the meaning of R, R, R and R for Hydrogen or alkanoyl, aralkanoyl or Am ^ yI is characterized in that one is a xylitol of the general formula CH ₂ -OH (II) CH-OH I
HIGH CH-OH CH ₂ -OH optionally in the presence of acid binders with an acylating agent of the general formula R-R - where R is mesyl or Tosyl stands, in which case R is halogen or halogenated 2, Method according to item 1, characterized in that for the preparation of compounds of general formula III, which fall within the scope of the compounds of general formula I, a xylitol of the general formula II with hydrogen halide reacted. 3 ~ acyl derivative of the general formula V - wherein R is as indicated above - optionally in the presence of an acid binder with an acylating the allgeraeii
above are defined - implemented. Acylating agent of the general formula R ~ R - wherein R and R are as 3 · Procedure according to point 2, marked dadurc that the reaction is carried out in an aqueous concentrated solution of hydrohalic acid with heating, preferably at a temperature of about 85 ⁰ C, 4. Process according to one of the items 1 to 3.ge characterized by treating for the preparation of 1,2-4,5-dianhydroxyl compound of the general formula III, wherein R is as defined in point, with a basic acid binder. 5 · Procedure according to point 4, marked » by treating the compounds of general formula III, wherein R is as defined above, with anion exchangers in hydroxyl form. 6. Process according to one of the items 2 to 5i, characterized in that, for the preparation of compounds, 1,5-dibromo-1,5-dideoxy-xyiitol, 1,5-dodo-1,5-dideoxy-xylitol and 1, 5-DiChIOrO-I ₁ S-dideoxy-xylit, 1,2-4,5-Dianhydfo-xylit of Formal IV with an aqueous hydrogen bromide solution or with aqueous hydrogen iodide solution or aqueous hydrochloric acid solution. 6 7 with acylating agents of the general formula E-R and thus obtains compounds of general formula III. 6 7 Wherein R and R are as defined above, and thus compounds of the general formula CH ₂ -R ⁶ (VI) CH-OH
R ^ö -0 - CH CH-OH
CH ₂ -R ⁶ receives or, if desired, the resulting dianhydroxylitol of the general formula IV, if appropriate in the presence of acid binder, -.17 - 21 2780 7, method according to any one of items 2 to 6, ge 127 8 0 net in that, for the preparation of the 3-aeyl derivatives of the general formula V, 1,2-4,5-dianhydro-'xylit of the formula IV in the presence of an acid binder with an acylating the O O "O general formula R -X or (K) ₂ O - wherein R and X are as defined above - converts, 7
indicates, in which case R is Y / acid - reacts, and desirably the compounds of the general formula CH ₂ -R ¹ (III) QH-OH HO - CH CH-OH Ü wherein R and Ii are defined above with a basic acid binder. 2127 8 0 Tel "treated and, if desired, the resulting dianhydro xylitol of the general formula (IV) CH-OH 'ft'
R -0-CH
ι CH-OH
CH ₂ -R ⁵
in the presence of an acid binder with an acylating agent Q ft Q general formula R -X or (R) 0 - wherein R is alkanoyl, aralkanoyl or aroyl and X is halogen - acylated and, if desired, the resulting 3-acyl derivative of the general formula CH RO-CH
ι CH il wherein R is as indicated above, optionally in the presence of Acid binders with Acylieruugsmitteln the general formula R -R 8. Procedure according to item 7 »characterized in that the reaction is carried out using trialkylamines; preferably tri (lower) alkylamines as acid binder. 9. Process according to item 7 or 8, characterized in that 3 ~ (p-phenylbenzoyl) -1,2-4,5-dianhydro-xylitol, 3 - (^ -phenylbutyryl) -1,2- is used to prepare 4 _s 5-dianhydro-xylitol or 3-acetyl-1.2-4.5-dianhydro-xylitol, 1,2-4,5-0ianhydro-xylitol of the formula IV in ^G egenwart of an acid binder with p-Phenylbenzoylchlbrid, 5- Phenylbutyryl chloride or acetyl chloride is reacted. 10. A process according to any one of items 2 to 9, characterized in that, for the preparation of the compounds of general formula VI - wherein R and R are as defined above - 11. The method according to item 10, characterized by the fact that the preparation of 3 "" (p-phenylbenzoyl) ~ 1,5-dibromo "* 1,5-dideoxy oxy-xylitol. the resulting 3- (p-phenylbenzoy!) ~ 1,2, 4,5-dianhydro-xylit reacted with hydrogen bromide solution. 12. Method according to item 7 or 8, characterized in that 3-tetoyl-1,2,5,5-dianhydroxylitol, a 1,2-4,5-dianhydroxylated xylit of formula IV in the presence of an acid binder with benzyl chloride. For this 1 page formulas