KR930005995B1 - Preparation of sterol derivative - Google Patents

Abstract

Quaternary ammonium substd. sterol derivs. of formula (I) are new. In (I), R1, R2 and R3 each = C1-18 alkyl or olefin; Q= inorganic strong acid anion such as Cl, Br or I; t = atomic value of Q; Rst = bone structure of sterol; n = 1-50. Pref. the Rst is a phytosterol such as sitosterol, campesterol or stigmasterol, cholesterol or lanosterol. Also claimed is the prepn. of (I) which comprises reacting sterol or ethoxy sterol with quat. ammonium epoxide salt of formula (II).

Description

Quaternary ammonium substituted sterol derivatives and preparation method thereof

The present invention relates to novel quaternary ammonium substituted sterol derivatives of general formula (I) and sterols or quaternary ammonium epoxide salts of ethoxylated sterols with general formula (II) It relates to a method for preparing a compound of formula (I) by reacting a quaternary ammonium amine salt.

Wherein Q is an anion of the strong inorganic acid Cl, Br or I, R ₁ , R ₂ , R ₃ is an alkyl group or olefin having 18 or less carbon atoms, the same or different, t is the valence of Q, n is 1 An integer up to 50 is shown, and Rst represents a sterol skeleton.

Sterols play a major role in the organization of lipids. [See Albert L. Lehninger. "Principles of Biochemistry" Worth Publishers, Inc., p. 304 (1982)]

In recent years, two major components of cholesterol and its precursor, desosterol (cholester-5,24-diene-3β-ol), have been found in the sterol fraction of internal lipids in wool. have. See: Dougles J. Gale, Raymond I. Logen, and Donald E. Rivett, Textile Research Journal, p. 539-542, (Sept 1987)]

Sterol is a natural substance present in vivo, and it has various biologically important functions. When it is used in cosmetics, it is excellent for skin and hair, and also has good effect on elasticity of skin and hair. Some of these are already commercialized, and they are either used as sterols themselves or by converting the sterol hydroxyls into ethoxylated structures to increase water solubility (eg, Generol 122, Generol 122E-25, Generol 122E). -16, Generol 122E-5; all manufactured by Henkel.

It is well known that cationic surfactants exhibit strong adhesion to negatively charged substrates under normal conditions, such as the surface of human hair or skin. [Surfactants in Cosmetics], Vol. 16, Marcel Dekker, 1985, p. 285-287]

There have been many examples of the use of quaternary ammonium compounds in hair products such as conditioning shampoos, and the literature has demonstrated their effectiveness. (Reference: XIth IFSCC Congress, Barcelona, 1986, Vol. I, p 335-369; Edward J. Murphy, Soap / Cosmetics / Chemical Specialities, p 38-40, Feb. 1980; Anthony M Schwartz and James W. Perry " Surface Active Agents "Interscience Publishers, Inc., New York, 151-200, 1949]

Most commercialized quaternary ammonium salts are based on the properties found in positively charged quaternary nitrogen atoms, which allow quaternized cations to be adsorbed on negatively charged surfaces such as skin or hair. .

Adsorption or adhesion of the quaternary ammonium salts increases with decreasing solubility in water, and increases with higher molecular weight of cationic hydrophobe (see K. Ohbu, T. Tamura, N. Mizushima). and M. Fukuda, Colloid & Polymer Si., 264, p. 798-802 (1986)].

The novel quaternary ammonium substituted sterol derivatives of the present invention are cationic surfactants incorporating quaternary ammonium groups in the sterols or sterolized ethoxylated compounds and have strong adhesion to polypeptide substrates such as skin or hair.

While conventional quaternary ammonium salts are mostly alkyl quaternary ammonium salts or dialkyl quaternary ammonium salts, the compounds of the present invention are introduced by introducing quaternary ammonium groups into sterols and sterol derivatives known to have excellent skin safety as natural substances. Skin safety is superior to quaternary ammonium salts or dialkyl quaternary ammonium salts.

Recently, quaternary ammonium derivatives of cholesterol have been prepared and used in the synthesis of polymerizable and nonpolymerizable liquid crystals. [Reference: S.K. Abid and D.C. Sherrington, Ploymer Communications, 1987, Vol 2, January p. 16-19; Iwhan Che and Kwang-Choon Chung, Macromolecules, 1984, 17, p 2935-2937].

However, unlike the compounds of the present invention, the quaternary ammonium derivatives of the above cholesterol are quaternary ammonium groups linked by ester bonds, which is clearly different from the method of combining the compounds of the present invention.

Sterols used in the preparation of the quaternary ammonium substituted sterol derivatives of the present invention include cholesterol and lanosterol found in animal cell membranes and several other sterols found in plant cell membranes.

Cholesterol, found in animal cell membranes, is found in the plasma membranes of eukaryotic cells such as red blood cells, liver and cytoplasmic neurons, but not in prokaryotes, but structurally has alcoholic hydroxyls on C-3. It is characteristic that there is.

Cholesterol, along with inlipid, forms the cell membrane and is involved in the formation of the myelin sheath of nerve tissue. [Reference: J. Invent Dermatol, 88, 709-713 (1987)] Lanosterol is also contained in the non-glycine part of wool fat and its structural formula (III) is as follows.

Phytosterols found in plant cell membranes include Stigmasterol, Sitosterol and Campesterol, and their structures are as follows. The so-called phytosterols are present everywhere in higher plants, most of which are sterols.

The main difference between the three sterols is found in the side branches attached to the C-17 carbons of the sterol skeleton.

Cholesterol molecules have an -OH group on C-3, which becomes a polar head group.

The molecule is a non-polar structure that is relatively fixed elsewhere.

Since the four rings are rigid, the presence of cholesterol reduces the fluidity of the membrane.

Hydroxy groups make up the polar moiety and the remainder of the molecule is hydrophobic.

The manufacturing method of the compound of general formula (I) which is the objective of this invention is as follows.

A) reacting a phytosterol selected from the compounds of formula (III) or formulas (IV) to (VI) with the quaternary ammonium epoxide of formula (II) or the above formulas (IV), (V) and (VI) Class 4 ammonium in compounds ethoxylated by n hydroxyl groups of the compound (an integer from n: 1-50) (product examples: Generol 122 E-5, Generol 122 E-16, Generol 122 E-25, etc., from Henkel) Epoxides are reacted in the presence of sodium hydroxide to form ether bonds and, if necessary, unreacted material is removed by gel chromatography to prepare compounds of formula (I).

B) The quaternary ammonium epoxide of general formula (II) used as the reactant of the present invention can be prepared by the following reaction.

The quaternary ammonium-substituted sterol derivatives of the present invention can be used in shampoos, hair rinses, hair treatments, creams, lotions, compacts, foundations and the like, and especially in hair cosmetics such as shampoos, hair rinses and hair treatments. It is extremely effective to indicate. Hereinafter, preparation examples of the present invention will be described.

[Example 1]

Preparation Method: After mixing the raw materials 1-6 and 10, and heated to 70 ℃ and stirred into the raw material 7-9 and cooled after stirring.

[Example 2]

Preparation Method: Raw materials 2-6 were mixed, heated to 65 ° C., stirred, raw materials 1-7 and 10 were added, and emulsified and cooled to 30 ° C.

[Example 3]

Preparation Method: Raw Material 1-9 was added at room temperature, stirred, and filtered.

The preparation of the quaternary ammonium-substituted sterol derivatives of the present invention is described in the Examples below.

Example 1

6 g of phytosterol (trade name: Generol 122, Henkel) obtained from soybean oil was added to 35 ml of isopropyl alcohol, and 17.5 g of 2,3-epoxypropyldimethyl dodecylammonium chloride solution (68% aqueous solution) was slowly added thereto. After raising to 40 ℃ slowly add about 0.6ml of 45% sodium hydroxide and proceed the reaction for 12 hours at 59 ℃. After the reaction is completed, 0.03 mol of hydrochloric acid is slowly added to adjust the pH of the solution to 7.0. Concentration as a vacuum rotary evaporator, after addition of isopropyl alcohol in excess, leaving a precipitate. The precipitate is filtered to filter and evaporated again with a rotary evaporator. After dissolving in the minimum amount of methanol that can be dissolved, the resultant is purified by gel chromatography using Sephadex LH-20 column as methanol as an eluent. The main fractions containing the purified product were collected and then evaporated to dryness by rotary evaporator to yield about 6.9 g of product.

Example 2

Add 6 g of phytosterol (trade name: Generol 122, Henkel) obtained from soybean oil to 40 ml of isopropyl alcohol and stir 22.4 g of 2,3-epoxypropyl dimethyl oleyl ammonium chloride solution (67% aqueous solution) slowly After the temperature was raised to 45 ° C., 0.8 ml of 45% caustic soda solution was slowly added, followed by reaction at 55 ° C. for 15 hours. After the reaction is completed, the pH of the solution is adjusted to 6.8 with acetic acid. Concentrate on a vacuum rotary evaporator, add excess isopropyl alcohol and leave for 12 hours to form a precipitate. Filter, filter out the precipitate and dry in vacuo.

Purified in the same manner as in Example 1 below to obtain about 7.1 g of a solid product.

Example 3

10 g of PEG-25 phytosterol (trade name: Generol 122 ES 25, Henkel Co., Ltd.) was dissolved in 80 ml of warmed water at 40 ° C in a reaction vessel with a fertilizer reed and a magnetie stirrer. 2,3-epoxy propyltrimethylammonium chloride and 0.1 ml of 20% NaOH were added, and the reaction proceeded with stirring at 55 ° C. for 5 hours. After the reaction is completed, acetic acid is added to adjust the pH of the reaction solution to 6.8-7.0.

The reaction mixture was concentrated under reduced pressure, and then 1 liter of isopropyl alcohol was added and left to stand to form a precipitate.

The precipitate was filtered off and the filtrate was dried in vacuo to give a pale yellow solid mixture.

For purification, water was chromatographed with Sephadex G-15 column as eluent, and the fractions containing the product were collected and vacuum evaporated to yield about 9.2 g of product.

Example 4

15.8 g (0.026 mol) of polyethoxylated cholesterol (EO = 5) was added to 20-30 ml of isopropyl alcohol, 0.2 ml of 10% NaOH was injected with stirring, and the temperature was raised to 30 ° C. to give 2,3-epoxypropyltrimethyl. 8.44 g (0.039 mol) of ammonium chloride (70% aqueous solution) are slowly added dropwise.

After completion of the raw material input, the mixture is kept at 50-55 ° C. for 5 hours, then neutralized with 0.156 ml of acetic acid and then maintained for another 30 minutes, after which excess isopropyl alcohol starts to precipitate. The filtrate was removed and the resulting product was dried in a 40-50 ° C. vacuum dryer for about 8 hours to yield about 17.6 g of product.

Example 5

25.08 g (0.026 mol) of polyethoxylated cholesterol (EO = 20) was added to 20-30 ml of isopropyl alcohol, 0.2 ml of 10% NaOH was injected with stirring, and the temperature was raised to 30 ° C. to give 2,3-epoxypropyltrimethyl. 8.44 g (0.039 mol) of ammonium chloride (70% aqueous solution) are slowly added dropwise.

After completion of the raw material input, the mixture is kept at 50-55 ° C. for 5 hours, then neutralized with 0.156 ml of acetic acid and then maintained for another 30 minutes, after which an excessive amount of isopropyl alcohol starts to precipitate. The filtrate was removed and the resulting product was dried in a vacuum dryer at 40-50 ° C. for about 8 hours to yield about 32.55 g of product.

Claims (5)

Quaternary ammonium substituted sterol derivatives of formula (I)

Wherein R ₁ , R ₂ and R ₃ are the same or different alkyl or olefin groups having 18 or less carbon atoms, Q is an anion of a strong inorganic acid, Cl, Br or I, t is the valence of Q, and Rst is It is a sterol skeleton structure, n shows the integer of 1-50. The quaternary ammonium-substituted sterol derivative according to claim 1, wherein the sterol skeleton represented by Rst is phytosterol such as Sitosterol, Campesterol, Stigmasterol or cholesterol or lanosterol. A process for preparing a quaternary ammonium substituted sterol derivative of formula (I) characterized by reacting a sterol or an ethoxylated sterol with a quaternary ammonium epoxide salt of formula (II).

Wherein R ₁ , R ₂ and R ₃ are the same or different alkyl or olefin groups having 18 or less carbon atoms, Q is an anion of a strong inorganic acid, Cl, Br or I, t is the valence of Q, and Rst is It is a sterol skeleton structure, n shows the integer of 1-50. The method according to claim 3, wherein the sterol is phytosterol or cholesterol or lanosterol, such as Sitosterol, Campesterol, Stigmasterol or the like. 4. The method according to claim 3, wherein the ethoxylated sterol is phytosterol or cholesterol or lanosterol, such as cytosterol, camphorsterol or stigmasterol to which 1 mol to 50 mol of ethoxy group is added.