IE41442B1 - Synthetic aliphatic hydrocarbon esters of phospholipid acids structural analogues thereof and a process for their manufacture and their use - Google Patents

Abstract

Synthetic alkyl esters of phosphatidic acids which correspond to naturally occurring phospholipids and can be used instead of them, where the phosphatidic acids have the accompanying formulae III and IV, in which the symbols R1, R2 and R3 have the meanings given in Patent Claim 1, and their structural analogues listed in Patent Claim 1 under a) to f) are prepared by A) reacting a primary alcohol of formula I R3-OH (I> with phosphorus oxychloride in the presence of an inert organic solvent; and B) reacting the resulting phosphorylating agent of the formula II with a suitable polyhydroxy compound in which one hydroxyl group is in free form and the remaining ones are protected. Elimination of the group R1-CO- or R2-CO- gives the corresponding lyso compounds from the compounds of the formulae III and IV. The products of the process can be employed instead of naturally occurring phospholipids and are particularly suitable as emulsifiers for the preparation of detergents and cleaning materials and as additives to foodstuffs and cosmetics.

Description

The present invention relates to synthetic aliphatic hydrocarbon esters of phospholipid acid, the structural analogues thereof, the physiologically tolerable salts thereof and to a process for their manufacture.

The present invention provides a compound of the general formula II W- P -0-R. (XV) I OH 'i wherein represents a saturated or unsaturated, straight or branched aliphatic hydrocarbon chain of up to 25 carbon atoms which may be substituted by one or more substituents selected from cycloalkyl and aromatic groups, and W is the residue of a polyhydroxy compound having at least 3 adjacent carbon atoms, the hydroxy groups of which may be protected, W being linked to the phosphorus atom via an oxygen atom.

The hydroxy groups of the radical W are preferably protected by groups which may be the same or different selected from ester, ether and ketal groups.

The present invention further provides a salt of a compound of the general formula (XV), preferably a physiologically tolerable salt, especially the sodium salt. - 3 41443 The present invention also provides a process for the preparation of a compound of the general formula (XV) or a salt thereof, which comprises A) reacting a primary alcohol of the general 5 formula r3oh I wherein R3 is defined as above, with phosphorus oxychloride in the presence of an inert organic solvent, and B) reacting the resulting phosphorylation agent of the general formula Cl \ PO-OR, II / 3 Cl wherein Rj is defined as above, with a polyhydroxy compound W-H, wherein W represents the residue of a polyhydroxy compound having at least 3 adjacent carbon atoms, which compound has one free hydroxy group, the further hydroxy groups being protected, to give, after hydrolysis, a compound of the invention.

In the above general formula (XV) R3 may stand for a saturated or unsaturated straight-chain or branched aliphatic hydrocarbon group having from 1 to 25 carbon atoms, advantageously in order of increasing preference 1 to 23, 1 to 21, 1 to 18 or 1 to 16; there should especially be mentioned in order of increasing preference the following ranges: 3 to 25, 3 to 23, 3 to 21, 3 to 18, 3 to 16, 3 to 14, 3 to 12, 3 to 10, 4 to 25, 4 to 21, 4 to 18, 4 to 16, 4 to 12, 6 to 25, 6 to 18 or 6 to 14 carbon atoms.

The group represented by may contain one or more double bonds and/or triple bonds and may be substituted by one or more cycloalkyl groups having for example 4 to 8, preferably 5 to 7) carbon atoms, or by 1 or more aromatic groups, for example phenyl and naphthyl groups and substituted phenyl groups.

Reaction (A) is carried out in the presence of an inert organic solvent, for example, a halogenated hydrocarbon, for example chloroform or carbon tetra10 chloride. The reaction is carried out in the absence of a base. The molar ratio of alcohol to phosphorus oxychloride is generally 1:2, but it may of course be varied within certain limits . For example, 1 mol of alcohol may be reacted with 1.7 to 2.3 mols of phosphorus oxychloride. The reaction is generally carried out under anhydrous conditions, and the reaction temperature is generally room temperature but temperatures of -10° to +80°C, for example from 20°C to 40°C, may be applied. The reaction time depends on the temperature chosen and may range from half an hour to 15 hours, generally from 10 to 12 hours, when carried out at room temperature.

When the reaction, which can be followed by thinlayer chromatography, is complete any excess phosphor25 us oxychloride and/or excess hydrochloric acid may be eliminated in a vacuum under hydrogen, for example, at 30 to 35°C. The alkyl alkenyl or alkynyl phosphoric acid dichloride remains as a residue. This alkyl, ; alkenyl or alkynyl phosphoric acid dichloride may be used directly for the subsequent phosphorylation reaction without further purification. A distillation is not necessary, and compared with known phosphorylation methods, this is a substantial advantage since many alkyl, alkenyl and alkynyl phosphoric acid di35 chlorides tend to decompose in an explosive manner.

The phosphorylation agent of the general formula II is very reactive and reacts with a large number of polyhydroxy compounds containing a free hydroxy group. The reaction is preferably carried out with exclusion of moisture in an inert organic solvent, for example a chlorinated hydrocarbon, for example chloroform or carbon tetrachloride. Other organic solvents, for example toluene or xylene or benzene may also be used; absolute solvents are however preferred.

The reaction of the phosphorylation agent with the polyhydroxy compound may be carried out within a wide range of temperatures for example from -10°C to +50°C, but preferably at room temperature. The reaction time used depends on the reaction temperature chosen, it ranges generally from half an hour to 5 or 6 hours. The phosphorylation reaction is preferably carried out in the presence of a base, for example, triethylamine.

The phosphorylation agent obtained according to this invention allows a number of aliphatic hydrocarbon esters of phospholipid acids to be obtained. Any polyhydroxy compound may be used which contains a free hydroxy group, other hydroxy groups of which being protected, for example by esterification, etherification, acetal or ketal formation. In general, the polyhydroxy compound used is a glyceride or a correspondingly higher homologue. It is thus possible according to the invention to phosphorylate not only erythritol, penitol and hexitol derivatives, but also cyclic polyhydroxy compounds, for example cyclic saccharic alcohols. Generally, monosaccaride derivatives and oligo-saccharide derivatives may be used according to the process of the invention. 41443 The process of the present invention may be carried out using racemic mixtures of pure optical isomers. A large variety of different aliphatic esters of phospholipid acids fall within general formula (XV). 1. Aliphatic hydrocarbon esters of phospholipid acids H.C-O-CO—R. 2| 1 H C-O-CO-RI 2 H„C- 0—PO-O-R, 2 I 3 OH (XII) H„C —0—CO—R 2, 1 H C- 0 — P0-0— R, I 1 I OH h2c—0— CO— r2 (IV) In the formulae III and IV, is defined as above, R* and R2 each stands for a saturated or unsaturated, straight-chain or branched aliphatic hydrocarbon group having 5 to 25, for example 5 to 21 or 5 to 18, and preferably 5 to l6, carbon atoms, which may be substituted by 1 or more, i.e. 2, 3, 4 or more substituents selected from, for example halogen atoms, fluorine, chlorine, bromine or iodine atoms, cycloalkyl groups and aromatic groups,for example there may be one or more halogen atoms or a cycloalkyl or aromatic substituent. If an aliphatic hydrocarbon is substituted by a cycloalkyl group,this may contain 4 to 8, preferably 5, 6 or 7j carbon atoms. If an aliphatic hydrocarbon group is substituted by an aromatic ring, this may, for example, be a phenyl ring or a naphthal - Ί 41442 ring which may also be further substituted.

Starting substances are racemic or optically active 1, 2- or 1,3-diglycerides having saturated, unsaturated, branched or halogenated fatty acids or fatty acids which contain a cycloalkane or aromatic ring. 2. Lyso analogues of compounds of Group 1 Starting compounds are l-acyl-2-benzyl glycerols or l-benzyl-2~acyl glycerols respectively. The phosphorylation reaction provides the lyso analogue by catalytic debenzylatipn. Unsaturated compounds are prepared with the help of protective groups which may be eliminated by a mild acid hydrolysis.

The starting compounds may also be obtained by biochemical methods from the compounds of Group X by enzymatic splitting with the phospholipases and A2 3. Analogues with saccharic alcohols H„C — 0 — CO—R , I (H C—0—CO— R) x H C'-O — PO — 0 -R, 2 I 3 OH (V) In the above formula V, R^ is defined as above, and R has the same meaning as R^ and R2, and X stands for an integer of from 1 to 5, i.e. 1,2,3, 4 or 5· Starting substances are acylated saccharic alcohols which contain a free hydroxy group.

Ether analogue^ of the compounds of Groups 1 to 3 and ether/ester analogues of the groups of compounds 1 and 3, for example.

II„C—0—R. 2 , 1 H C— 0 —R„ H„C—0—P0 —0 —R. 2 , 3 OH H„C—0—R z| 1 H C—0—P.O—0-R* H,C 2 x OH 0—R_ (VI) (VII) In the formulae VI and VII, R^, Rg and R^ are defined as above.

Starting substances are 1,2- and 1,3-di(alkyl-, alkenyl- and alkynyl)-glycerol ethers or acylglycerol aliphatic hydrocarbon ethers. The aliphatic hydrocarbon radical may be saturated, unsaturated, branched or halogenated and may also contain a cycloalkane group or an aromatic group. . 0-Mono- and di-[alkyl-, alkenyl- and alkynyl]15 methylidene glycerol phosphoric acid aliphatic hydrocarbon esters. H9C-0 . R, zC\ H C —θ' XRg V-°x Λ 1 < νχ *2 H2C-0 P0-0-R3 H2C-O-PO-O-R3 (VIII) 1 OH OH (Vila) - 9 41442 H2R2 /\ HC-0 H H.C-0 R. 2I \ / 1 H C-0 C\ H-C - 0 - PO - 0 - R2 ι 3 H.C-O'PO-O-R. 2 I 3 OH OH (IX) (IXa) In the above formulae VIII and IX, R^, R2 and R^ are defined as above Starting substances are the 1,2- and 1,3-05 mono-or di-(alkyl-, alkenyl- and alkynyl-) methylidene glycerols which may be obtained from glycerol or the 2-benzyl ether thereof by reaction with a ketone or aldehyde. The ketones or aldehydes may be saturated, unsaturated, branched or halogenated and may also contain a cycloalkane or an aromatic ring. 6. Other 0-methylidene glycerol phosphoric acid, aliphatic hydrocarbon esters h2c Η C 1 h2c h2c η2ο PO-O-R. \ 3 (XI) -10In the above formulae, Rg is defined as above, and y stands for an integer of from 5 to 32, advantageously in order of increasing preference 5 to 28, to 24, 5 to 18, 5 to 16, 5 to 14, 5 to 12, 5 to 10 or 5 to 8.

Starting substances are 0-1,2- and 1,3-cycloalkylidefie- glycerols which may be obtained from glycerol or 2-benzylglycerol by reaction with the corresponding cycloalkanone. 7· Aliphatic hydrocarbon esters of desoxylysophospholipids H.C - 0 -CO — R, 2I 1 (CH„)m (XII) I 2 H.C - 0 -PO - 0 - R. , 3 OH H3C3I (CH2)m‘ H £ - 0 - CO - R (XIII) I 1 H.C - 0 - PO - 0 - R, 2 I 3 OH H3C ; (2)ρ H C - 0 - CO - Rx (χιν) (CH2)q H.C - 0 - PO - 0 - R, 4 i 3 OH 41443 In the above formulae, R^ and Rg are defined as above, and m stands for an integer of from 1 to 14, preferably from 1 to 13, m' stands for zero or for an integer of from 1 to 14, preferably 0 or from 1 to 13, and p + q = m'.

As starting substances, the monoacylalkane diols are preferred. The aliphatic diols may be saturated, unsaturated, branched or halogenated and may also contain a cycloalkane or an aromatic ring. 8. Ether analogues of compounds of Group 7.

Methods for the preparation of the said starting substances are known (A.J. Slotboom and P.P.N. Bonsen Chem.Phys,Liquids (1970), pages 301 to 398).

The compounds of the invention formulae XV and III to VI have valuable pharmacological properties and they are potent surfactants which,owing to their structural analogy with the phospholipids present in the cell membranes, are able to influence the surface activity of these membranes. Their negative charge at physiological pH-values is, moreover, capable of influencing the charge of biological membranes. Owing to these properties, these substances can be expected to modify the activity of pharmaceutically active substances increasing their absorability and their distribution in the organism to which they are administered. The compounds are therefore useful as additives in pharmaceutical preparations.

The compounds of formulae III to VIII are further more, readily dispersible in water and give emuls41443 ions which are stable over a wide pH range. It is surprising that these emulsions are still stable at a pH of as low as 1.0 whilst, for example, emulsions comprising lecithin precipitate in flakes at a pH of only 2.0. Dispersions of the said compounds are therefore capable of passing unchanged through the stomach (pH 1.5) and of improving, for example, the absorbability of fats.

The compounds of formulae III to VIII are potent surfactants and have a lytic activity on natural membranes, for example, erythrocytes. They may, therefore, be used in many ways to disintegrate such membranes or, when applied in sublytic dosages, to modify the properties of these membranes, which again may influence the activity of pharmaceutical compositions.

The invention accordingly provides pharmaceutical preparations which comprise a compound of the general formula ® W - P - OR, (XV) I J OH wherein R represents a saturated or unsaturated, straight or branched aliphatic hydrocarbon chain of up to 25 carbon atoms which may be substituted byi one or more substituents selected from cycloalkyl and aromatic groups, and W is the residue of a polyhydroxy compound, the hydroxy groups of which may be protected, W being linked to the phosphorus atom via an oxygen atom, or a physiologically tolerable salt thereof, in admixture or conjunction with a pharmac41442 eutically suitable carrier. The compound of the general formula XV or the salt thereof may be the sole active ingredient or one or more other pharmacologically active substances may also be present.

Compounds of the general formula XV in which W is a residue of a polyhydroxy compound having less than 3 adjacent carbon atoms may be prepared by a process analogous to the process of the invention.

The compounds of the general formula (XV) gen10 erally have very good emulsifying properties. As they have a structure similar to that of natural products, they are physiologically acceptable in food-stuffs and may therefore be used for a variety of applications. When added to margarine, they bring about a better linkage to water, thus preventing it from splashing in the frying pan, and imparting to it butter-like properties when used for frying. They may be used in sweets for emulsifying syrup with fat and also for preventing the fat from becoming rancid.

When used in cosmetic preparations and for making soaps, a small amount of a compound of the general formulae (XV) improves the suppleness and absorption of, for example, ointments, creams, tooth pastes, and soaps.

Accordingly the other aspects of the invention are cosmetic preparations and soaps, detergent preparations and food stuffs, especially margarine, each of which comprises a compound of the general formula, (yy) or a physiologically tolerable salt thereof.

There may especially be mentioned pharmaceutical preparations, cosmetic preparations and soaps and foodstuffs containing a compound of the formula III to XIV shown above or containing a compound of formula XII wherein m is 0.

The following Example 2 illustrates the invention. Example 1 illustrates the preparation of a starting material.

Example 1 General preparation of (alkyl, alkenyl- and alkynyl-)-phosphoric acid dichlorides: 80 g (0,6 mol) of POCl^ (freshly distilled, boiling point 10$ to 107°C) in 100 ml of absolute chloroform (distilled for 90 minutes with circulation over were placed in a three-neck flask equipped with cooler, dropping funnel and nitrogen inlet tube. While stirring by means of a magnetically operated stirrer nitrogen was slowly fed in, and 0.3 mol of the desired alcohol in 50 ml of absolute chloroform was added dropwise. The mixture was stirred for 12 hours at room temperature, and the resulting hydrogen chloride, excess POCl^ and chloroform were eliminated at 30°C in a rotary evaporator. To eliminate any trace of FOCI3, 50 ml of toluene were added and likewise drained off.

The remaining oily substance, i.e. the alkyl, alkenyl or alkynyl phosphoric acid dichloride, can be reacted further without purification. Distillation was performed on some of low boiling alkyl phosphoric acid dichlorides and the following boiling points were observed: boiling point at 10 mm Hg CH3-O-PO-C12 44 to 47°C c2h5-o-po-ci2 54 to 56°C C3H7-O-PO-C12 66 to 68°C c4h9-o-po-ci2 85 to 87°C The reaction ] provided a yield of 9θ to 100% and can be followed by thin-layer chromatography.

Example 2 General preparation of aliphatic hydrocarbon esters of phospholipid acid and of structural analogues thereof: The phosporylation agent prepared in Example 1 (0.3 mol) was dissolved in 100 ml of absolute chloro15 form (distilled for 9θ minutes with circulation over P20j), and the solution was cooled to 0 to 5 in an ice bath. While stirring by means of a magnetically operated stirrer, 60 g (0.6 mol) of absolute triethylamine (dried over lithium aluminium hydride and freshly distilled) were added dropwise to 50 ml of absolute chloroform. The ice bath was then replaced by a water bath of 20°C. While stirring steadily, a solution of the other starting substance (0.15 mol) in 150 mol of absolute chloroform was added dropwise to the phosporylation mixture. Checking by means of thin-layer chromatography ensured that the reaction was almost complete after the dropwise addition.

After another 6 hours at 40°C the reaction mixture was freed in a rotary evaporator at 35°C from solvent, and the residue was taken up in 450 ml of tetrahydrofuran. Whilst stirring; 1M sodium acetate solution of pH 8.4 was added to the suspension or solution of the reaction mixture in tetrahydrofuran until the water phase remained neutral (pH about 7)· For this purpose, about 450 ml of IM sodium acetate solution had to be added. The hydrolysed reaction product was extracted as the sodium salt by means of 45θ ml of diisopropyl ether. The water phase was again extracted by means of 200 ml of diisopropyl ether. The combined diisopropyl ether extracts were mixed while stirring with 10 g of sodium carbonate to eliminate water and to ensure complete conversion of the reaction product into the sodium salt.

For the preparation of a derivative having less than a total of 14 carbon atoms, the reaction solution was acidified with HC1 (pH about 2) prior to the extraction with diisopropyl ether. Derivatives having a shorter chain were better extracted as the free acid and could be crystallised by carefully adding sodium methylate in methanol.

The diisopropyl ether phase was filtered and the filtrate was evaporated in vacuo. The residue was recrystallised from an ethyl methyl ketone/ acetone mixture. Generally the resulting reaction product was analytically pure. Otherwise a complete purification of the products was achieved by chromatography on silica gel. The yield of analytically . pure product varied between 70 and 90% (calculated on the starting products used).

The following compounds were prepared: (The term sn mentioned hereinafter indicates that the compound can occur in .several different stereoisomeric forms).

Compound of Group 1: sn-12,-dimyristoyglycerol-3-phosphoric acid methyl ester, as sodium salt, <'32H62Na°8P (628.8) calculated: C 61.12% H 9.94% P 4.93% The data found complied with the calculated values Compound of Group 2: sn-l-myristoylglycerol-3-phosphoric acid methyl ester, as sodium salt, C^H^NaO^P (418.5). calculated: C 51.67% H 8.67% P 7-40% The data found complied with the calculated 15 values.

Compound of Group 3: 1,2,3,4,5-pentapalmitoyl-D-mannitol-6-phosphoric acid butyl ester, as sodium salt, CygH^^NaO^Pf 1532.3) calculated: C 70.55% H 11.32% P 2.02% The data found complied with the calculated values. 41443 Compound of Group 5: 1,2-0- Oiheptadecylmethylidene—glycerol—3—phosphoric acid octyl ester, as sodium salt, NaO6P(795.21) calculated: C 69.4«$ H 11.66$ F 3.90$ The data found complied with the calculated values.

Compound of Group 7: 01eoylhexane-l,6-diol-phosphoric acid isopropyl 10 ester, as sodium salt, C2yH32NaOgP(520.6 8) calculated: C 61.57$ H 9.52 P 5-88% The data found complied with the calculated values.

Compound of Group 8: Propane-1,3-diol-hexadecyl ether phosphoric acid hexyl ester, as sodium salt, C26H52NaO5F(486·7) calculated: C 61.70$ H 10.77$ P 6.37$ The data found complied with the calculated values.

Claims (30)

1. A compound of the general formula XV W - I - 0 - R, (XV) I 3 OH wherein Rg represents -a saturated or unsaturated 5 straight or branched aliphatic hydrocarbon chain of up to 25 carbon atoms which may be substituted by one or more substituents selected from cycloalkyl and aro matic groups, and W is the residue of a polyhydroxy compound having at least 3 adjacent carbon atoms the 10 hydroxy groups of which may be protected, W being linked to the phosphorus atom via an oxygen atom.

2. A compound as claimed in claim 1 wherein the hydroxy groups are protected by groups which may be the same or different selected from ester, ether and 15 ketal groups.

3. A compound as claimed in claim X, wherein W represents H 2 C - 0 - CO - R t I HC - 0 I H 2 C - 0 - CO - R H„C - 0 - CO - R. 2, 1 H C - 0 - CO - R, OR I 2 h 2 c - o wherein R^ and R 2 , which may be the same or different 20 each stands for a saturated or unsaturated, straight or branched aliphatic hydrocarbon chain of 5 to 25 carbon atoms which may be substituted by one or more substituents selected from halogen atoms, cycloalkyl and aromatic groups, the ether analogues thereof, . wherein W represents H„C -0-R, H2C - 0 - R, 2| 1 I 1 HC-O-R, OR HC-OI 2 I h 2 c - 0 - H 2 C - 0 - R 2 5 the mixed ether/ester analogues thereof, and the lyso analogues of any of the aforementioned compounds and analogues.

4. A compound as claimed in claim 1, wherein W represents h 2 c - 0 - CO - r 2 (H C - 0 - CO - R)x I h 2 c - 0 wherein R has the same meaning as R^ or R 2 as defined in claim 3 and x is an integer from 1 to 5, the ether analogues thereof and the ether/ester analogues thereof.

5. A compound as claimed in claim 1, wherein W represents H 9 C z l H C 0^ ^R 2 h 2 c - 0 H_C - 0 R 1 X H C - 0 \ H H i'\\ V - οΛ r 2 / E i OR H C - 0 \ 1 X x H 2 C - o z \ Rj and R 2 being as defined in claim 3.

6. A compound as claimed in claim 1, wherein W represents h 2 c - 0 x HC-O / I h 2 c - 0 C^_JCH 2 )y OR H, C — 0 2 I \ H C - 0' C (CH 2 )y h 2 c LoX'· wherein y is an integer of from 5 to 32.

7. A compound as claimed in claim 1, wherein W represents II, C - 0 - CO - R 2 I (CH,)m I 2 h 2 c - 0 (CH,)m' I 2 H C - 0 - CO - R, I 1 h 2 c - 0 10 41443 OR (CH,)p I 2 HC - 0 - CO - R I (CH )q I 2 h 2 c - 0 wherein R^ has the meaning given in claim 3, m is an integer of from 1 to 14, m' is zero or an integer of 5 from 1 to 14 and p + q = m', and ether analogues thereof.

8. A salt of a compound as claimed in any one of claims 1 to 7·

9. A physiologically tolerable salt of a compound 10 as claimed in any one of claims 1 to 7·

10. l,2-Dimyristoylglycerol-3-phosphoric acid methyl ester.

11. 1,2-Myristoylglycerol-3-phosphoric acid methyl ester. 15

12. l,2,3,4,5-pentapalmitoyl-D-mannitol-6-phosphoric acid butyl ester.

13. 1,2-0-Diheptadecylmethylidene-glycerol-phosphoric acid octylester.

14. 01eoylhexane-l,6-diol-phosphoric acid isopropyl 20 ester.

15. - Propane-1,3-dlol-hexadecyl ether phosphoric acid - 23 41442 hexyl ester.

16. A sodium salt of a compound as claimed in any one of claims 10 to 15.

17. A process for the manufacture of a compound as 5 claimed in claim 1 or a salt thereof, which comprises (A) reacting a primary alcohol of the general formula R 3 0H in which R^ is defined as in claim 1, with phosphorus 10 oxychloride in the presence of an inert organic solvent, and (B) reacting the resulting phosphorylation agent of the general formula Cl \ PO-OR, / Cl j5 in which R^ is defined as above, with a polyhydroxy compound W-H wherein W represents the residue of a polyhydroxy compound having at least 3 adjacent carbon atoms, which compound has one free hydroxy group the further hydroxy groups being protected, to give, after 2q hydrolysis, a compound as claimed in claim 1.

18. A process as claimed in claim 17, wherein the reaction (B) is carried out in the presence of an inert organic solvent. - 24

19. A process as claimed In claim 18, wherein the reaction (B) is carried out in the presence of an organic base and with the exclusion of moisture.

20. A process as claimed in claim 17, carried out 5 substantially as described in Example 2.

21. A compound of formula (XV) as claimed in any one of claims 1 to 16, whenever prepared by a process as claimed in claim 17.

22. A pharmaceutical preparation which comprises a 10 compound of the general formula II w -p - o - R (xv) I 3 on wherein Rg represents a saturated or unsaturated, straight or branched aliphatic hydrocarbon chain of up to 25 carbon atoms which may be substituted by 15 one or more substituents selected from cycloalkyl and aromatic groups, and W is the residue of a polyhydroxy compound, the hydroxy groups of which may be protected, W being linked to the phosphorus atom via an oxygen atom, or a physiologically tolerable salt thereof, in 20 admixture or conjunction with a pharmaceutically suitable carrier.

23. A pharmaceutical preparation which comprises a compound as claimed in any one of claims 1 to 7 and 9 to 16 in admixture or conjunction with a pharmaceutic25 ally suitable carrier. 25 41442

24. A pharmaceutical preparation as claimed in claim 22 or claim 23, which also comprises one or more other pharmacologically active substance(s),

25. A cosmetic preparation or a soap which comprises 5 cosmetic material or a soap and a compound of the general formula (XV) as specified in claim 22.

26. A cosmetic preparation or a soap which comprises cosmetic material or a soap and a compound as claimed in any one of claims 1 to 7 and 9 to 16. 10

27. - A detergent preparation which comprises a detergent and a compound as claimed i.n any one of claims 1 (.0 7 and 9 to 16.

28. A foodstuff composition which comprises a foodstuff and a compound of the general formula (XV) as 15 specified in claim 22.

29. A foodstuff composition which comprises a foodstuff and a compound as claimed in any one of claims 1 to 7 and 9 to 16.

30. A foodstuff composition as claimed in claim 28 20 or claim 29, which is margarine.