DE19617939A1 - Chiral amphiphilic compounds used as e.g. surfactants, emulsifiers or aqueous hydrogenation reaction auxiliary aids - Google Patents

Abstract

Chiral micelle-forming compounds of formula (I) and their hydrogenated derivatives of formula (II) are new: R<1> = R<2> = COalkyl, COaryl or H; or R<1> = COalkyl, COaryl or H; and R<2> = alpha -D-glucopyranosyl (maltose), beta -D-glucopyranosyl (lactose), or beta -D-glucopyranosyl (cellobiose); m = at least 8 ; and n = at least 4.

Description

The invention relates to new chiral amphiphiles and a process for their preparation as well the use of these micelle formers.

It has been known for decades that the linkage of natural oils and fats with Carbohydrates are used to prepare surfactants (Ames, G. R., Chem. Rev. 1960, 60, 541). Due to the amphiphilic properties, the easy biodegradability, the unbe Limited availability and toxicological safety gain non-ionic Carbohydrate-based surfactants are becoming increasingly important today. They are considered Emulsifiers in the food and cosmetic industries and also as specialty surfactants, Wetting agents, solubilizers or membrane-active species used for biological systems. Known carbohydrate surfactants are, for example, sorbitan fatty acid esters (Tween) (Biermann, M., Lange, F., Piorr, R., Ploog, U., Rutzen, H., Schindler, J., Schmid, R. in Synthesis of Surfactants. In .: Falbe (ed.): Surfactants in Consumer Products-Theory, Technology and Application, Springer-Verlag, Heidelberg 1987, pp. 23-132), which are easily caused by esterifications Sorbitol can be obtained. Through additional ethoxylation reactions Water solubility of this type of compound increased. However, there are several reactions steps to the target product are necessary, and connections can be different Degrees of ethoxylation occur side by side.

It is also known that sucrose mono fatty acid esters, their regioselective preparation however, creates difficulties and thus necessitates difficult separation processes, are surface-active substances with interesting properties. You will be special applications used (Desai, N.B., Lowicki, N., Parfuem. Kosmet. 1983, 64, 463). In addition, fatty acylglucamines and fatty acylglucamides play in due to the difficulties in their manufacture has only a limited role.

Due to the high availability and low price of glucose, the alkyl glucosides come across (Raths, H.-Ch., Endres, H., Hensen, H., Tesmann, H., Lecture 3rd World Surfactant Congress, London 1992) and alkyl polyglucosides (Hughes, F.A., Lew, B.W., J Am. Oil Chem. Soc. 1970, 47, 162) of particular interest. It is known that these are ethoxylated Fatty alcohols are thicker and very good with other detergent ingredients correlate. They are mild on the skin and have good ecotoxicological data (Schulz, P. T., BACS Symposium 33, 1991).  

It is also known that fatty alcohol polyglycol ethers are behind the soaps and alkylbenzene Take 3rd place in sulfate consumption.

A combination of fatty alcohol polyglycerol ethers and carbohydrates, as in the example of Described sorbitans can lead to optimal surfactant properties.

The object of the invention is to create new surfactant structures from carbohydrate building blocks and To provide fatty alcohol polyglycol ethers, a synthetic process to be developed, which, in contrast to sorbitans, the target compounds in a simple chemo- and regioselective methods, characterized by a few synthetic steps, and avoids the disadvantages mentioned above.

This task is solved according to the requirements.

The new compounds have the general formula I:

in the
R1 = R2 = CO alkyl, CO aryl or H.
or
R¹ = COAlkyl, COAryl or H and
R² = α-D-glucopyranosyl (maltose), β-D-galactopyranosyl (lactose) or β-D-glucopyranosyl (cellobiose) and
n is an integer 4 and
m is an integer 8
represent.

These new compounds can also be in hydrogenated form (see Example 9); she then have the general formula II

with the meanings given above.

According to the invention, these new amphiphiles are started in a few steps from commercially available starting materials, obtained according to Scheme 1.

Scheme 1

The first reaction step (Lewis acid catalyzed allyl rearrangement reaction) is carried out at Temperatures between -10 ° C and 50 ° C, preferably carried out at 25 ° C. For All Lewis acids familiar to the person skilled in the art can be used, preferably tin tetrachloride. Aprotic polar solvents serve as reaction medium, acetonitrile is used with advantage, with short reaction times processing is particularly easy. Furthermore, the solvent be recovered.  

The so obtained according to the invention and by hydrophilic and hydrophobic groups excellent compounds allow stoichiometric and catalytic reactions in Water as a favored reaction medium. Since their chirality is in the hydrophilic part, what chiral recognition is possible, they are both chemically and physiologically of great importance.

The following chiral forms of the new micelle formers are produced:

where R₃ = O (CH₂CH₂O) _n C _m H _{2m + 1} with n 4 and m 8.

Due to the optical transparency of the micelle in solution, they are also suitable for suitable for photochemical reactions. So it is known that amphiphiles are stereoselective Accelerate reactions in water (I. Grassert, E. Paetzold, G. Oehme, Tefrahedron 1993, 49, 6605). It is also known that hydrogen bonds cause micelle formation favor (P. Venkatesan, Y. Cheng, D. Kahne, J Am. Chem. Soc. 1994, 116, 6955) and that aggregates of this kind can transfer chirality to the substrate (I. Grassert, V. Vill, G. Oehme, J. Mol. Catal. A in press).  

The amphiphilic compounds prepared according to the invention also form micelles in water, which like organic reactions that tolerate the solvent water Extensor syntheses, Michael additions, hydrogenations, hydroformylations and others, allow.

In their presence, hydrogenation reactions to pure water are extremely accelerated and achieved enantiomeric excesses in the hydrogenation of dehydroamino acid derivatives, which are comparable to or exceed those in methanol as a solvent. So is for example, a direct comparison of Example 10 with Examples 11 to 17 significant activation increase of 90 min. up to 5 min. Half-life (t / 2) and a Enantioselectivity increase from 78% ee up to 97% ee with the addition of amphiphiles ascertain. The process of hydrogenation is carried out at temperatures between 0 ° C and 50 ° C, preferably at 25 ° C and a hydrogen pressure between 0.01 MPa to 10 MPa, preferably carried out at 0.1 MPa. The catalyst / amphiphile ratio is preferably 1/20, which is above the critical micelle concentration. This process also has the particular advantage of easy separability from the catalyst the catalyst product mixture with it, for example, due to the Catalyst concentration in the amphiphilic range by separating z. B. by Can make membranes particularly efficient, but also by simple extraction processes is realized.

The compounds shown are biodegradable surfactants that are used particularly in the cosmetic industry and in the medical field can.

The invention is illustrated by the following examples, but without restricting it.

example 1 General rule

To a solution of 9.1 mmol acetyl-protected 1,2-dideoxy sugar and 9 mmol polyoxy Ethylene ether in 50 ml of acetonitrile, 0.5 ml of tin tetrachloride are added dropwise with stirring. The The reaction is monitored by means of thin layer chromatography (toluene / ethyl acetate = 4/1). After 30 min. the reaction is over. For working up with 5 g of potassium carbonate neutralized, the solid constituents are filtered off and the solvent is stripped off. The The product is purified by column chromatography (chloroform / methanol = 9/1). The Mobile solvent is drawn off and the product is dried under an oil pump vacuum.  

4,6-di-O-acetyl-1- (O-dodecyldecaoxyethylene) -2,3-dideoxy-hex-2-eno-p-yranoside (1a)

With tri-O-acetyl-D-glucal and decaoxyethylene dodecyl ether. Yield; 10.5 g (68%), yellow syrup, [α] = + 38.2 ° (CHCl₃, c = 0.96), IR (capillary) cm ^-1 :
1745 (C = O).
C₄₂H₇₈O₁₆ (839.07 g / mol), calc .: C, 60.12; H, 9.37. Found: C, 60.37; H, 9.52.
1 H-NMR (CDCl₃): δ = 5.84 ppm (m, 2H, H-2,3), 5.30 (m, 1H, H-4), 5.05 (s, 1H, H-1), 4.24 (dd, 1H , H-6a, J _{6a, 6b} = 12.2, J _{6a, 5} = 5.2), 4.14 (dd, 1H, H-6b, J _6b.5 = 2.4), 4.08 (m, 1H, H-5), 3.70 - 3.40 (m, 10 CH₂CH₂O, αCH₂), 2.07 (s, 3H, H-acetyl), 2.05 (s, 3H, H-acetyl), 1.60 (m, 2H, βCH₂), 1.20 (m, 18H, CH₂) , 0.85 (t, 3H, CH₃, J _{CH2, CH3} = 7.0).
13 C-NMR (CH₃Cl): δ = 70.60 (C = O), 170.12 (C = O), 129.11 (C-2), 127.80 (C-3), 94.61 (C-1), 66.95 (C-4) , 65.35 (C-5), 70.46-61.62 (C-6, OCH₂), 31.80-22.56 (CH₂), 20.84 (acetyl-CH₃), 20.66 (acetyl-CH₃), 13.99 (CH₃) ppm.

Example 2 4,6-di-O-acetyl-1- (O-cetyleicosaoxyethylene) -2,3-dideoxy-hex-2-eno-p-yranoside (2a)

With tri-O-acetyl-D-glucal and eicosaoxyethylene cetyl ether. Yield: 15.2 g (62%), yellow syrup, [α] = + 23.4 ° (CHCl₃, c = 1.15), IR (capillary) cm ^-1 :
1743 (C = O).
C₆₆H₁₂₆O₂₆ (1335.71 g / mol), calc .: C, 59.34; H, 9.51. Found: C, 58.96; H, 9.49. 1 H-NMR (CD₃OD): δ = 5.84 ppm (m, 2H, H-2,3), 5.25 (m, 1H, H-4), 5.05 (s, 1H, H-1), 4.20 (dd, 1H , H-6a, J _{6a, 6b} = 12.2, J _{6a, 5} = 5.2), 4.14 (dd, 1H, H-6b, J _{6b, 5} = 2.4), 4.08 (m, 1H, H-5), 3.70 -3.40 (m, 20 CH₂CH₂O, αCH₂), 2.07 (s, 3H, H-acetyl), 2.05 (s, 3H, H-acetyl), 1.60 (m, 2H, βCH₂), 1.20 (m, 18H, CH₂) , 0.85 (t, 3H, CH₃, J _{CH2, CH3} = 7.0).
13 C-NMR (CH₃Cl): δ = 170.60 (C = O), 170.12 (C = O), 129.02 (C-2), 127.69 (C-3), 94.51 (C-1), 67.71 (C-4) , 63.33 (C-5), 70.46-61.62 (C-6, OCH₂), 31.80-22.56 (CH₂), 20.84 (acetyl-CH₃), 20.66 (acetyl-CH₃), 13.99 (CH₃) ppm.

Example 3 4,6-di-O-acetyl-1- (O-dodecyltricosaoxyethylene) -2,3-dideoxy-hex-2-en-o-pyranoside (3a)

With tri-O-acetyl-D-glucal and tricosaoxyethylene dodecyl ether. Yield: 13.6 g (52%), yellow syrup, [α] = + 14.1 ° (CHCl₃, c = 0.923), IR (capillary) cm ^-1 :
1744 (C = O).
C₆₃H₁₃₀O₂₉ (1411.76 g / mol), calc .: C, 57.85; H, 9.28. Found: C, 58.86; H, 9.39. 1 H-NMR (CDCl₃): δ = 5.84 ppm (m, 2H, H-2,3), 5.30 (m, 1H, H-4), 5.05 (s, 1H, H-1), 4.24 (dd, 1H , H- 6a, J _{6a, 6b} = 12.2, J _{6a, 5} = 5.2), 4.14 (dd, 1H, H-6b, J _{6b, 5} = 2.4), 4.08 (m, 1H, H-5), 3.70 -3.40 (m, 23 CH₂CH₂O, αCH₂), 2.07 (s, 3H, H-acetyl), 2.05 (s, 3H, H-acetyl), 1.60 (m, 2H, βCH₂), 1.20 (m, 18H, CH₂) , 0.85 (t, 3H, CH₃, J _{CH2, CH3} = 7.0).

Example 4 6-O-acetyl-4-O- (2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl) -1- (O-dodecyltricosaoxy ethylene) -2,3-dideoxy-α-D-erythro-hex-2-eno-pyranoside (4a)

With hexa-O-acetyl-D-maltal and tricosaoxyethylene dodecyl ether. Yield: 4.8 g (32%), yellow syrup, [α] = + 48.6 ° (CHCl₃, c = 0.92), IR (capillary) cm ^-1 :
1750 (C = O).
C₈₀H₁₄₆O₃₇ (1700.02 g / mol), calc .: C, 56.52; H, 8.65. Found: C, 55.85; H, June 8th 1 H-NMR (CDCl₃)
1 H-NMR (CDCl₃): δ = 5.95 (m, 1H, H2), 5.90 (m, 1H, H-3), 5.45 (m, 2H, H-1, H-3 '), 5.21 (d, 1H , H-1 ′), 5.00 (t∼dd, 1H, H-4 ′), 4.78 (dd, 1H, H-2 ′), 4.25-4.80 (m, 7H, H-6, 6 ′, 5, 4, 5 ′), 3.8-3.4 (m, 94H, H-CH₂), 2.01, 1.98, 1.94, 1.90 (s, 15H, H-acetyl); 1.60 (m, 2H, H-CH₂), 1.4-1.3 (18 H, H-CH₂), 0.8 (t, 3H, H.CH₃).

Example 5 General working instructions

A solution of 1.5 mmol of the compounds shown in Example 1-4 in 50 ml of methanol is mixed with NaOCH₃ until a basic reaction. The reaction becomes thin followed by chromatography (chloroform / methanol = 9/1). After an hour the reaction is over completed. It is neutralized with an acidic ion exchanger (Amberlite IRC-50). From ions Exchanger is filtered off, the solvent is evaporated off and the product is oil-pumped vacuum dried.

4,6-di-hydroxyl-1- (O-dodecyldecaoxyethylene) -2,3-dideoxy-hex-2-eno-p-yranoside (1b)

With 1a.
Yield: 1.7 g (98%), yellow syrup, [α] = + 12.6 ° (CHCl₃, c = 0.96), IR (capillary) cm ^-1 :
(C = O) band has disappeared.
C₃₈H₇₄O₁₄ (755.00 g / mol), calc .: C, 60.45; H, 9.88. Found: C, 59.49; H, 9.99. 1 H-NMR (CDCl₃):
δ = 5.94 ppm (m, 1H, H-2), 5.75 (m, 1H, H-3), 5.00 (m, 1H, H-1), 4.4-3.4 (m, 46H, H-CH₂, H- 6a, 6b, 5, 4, αCH₂), 1.60 (m, 2H, βCH₂), 1.20 (m, 18H, CH₂), 0.85 (t, 3H, CH₃, J _{CH2, CH3} = 7.0).

Example 6 4,6-di-hydroxyl-1- (O-cetyleicosaoxyethylene) -2,3-dideoxy-hex-2-eno-p-yranoside (2b)

With 2a yield: 1.7 g (94%), yellow syrup, [α] = + 10.9 ° (CHCl₃, c = 1.2), IR (capillary) cm ^-1 :
(C = O) band has disappeared.
C₆₂H₁₂₂O₂₄ (1251.63 g / mol), calc .: C, 59.49; H, 9.82. Found: C, 59.95; H, 9.76.
1 H-NMR (CDCl₃): δ = 5.94 ppm (m, 1H, H-2), 5.70 (m, 1H, H-3), 4.95 (m, 1H, H-1), 4.4-3.4 (m, 46H , H-OCH₂, H-6a, 6b, 5, 4, αCH₂), 1.55 (m, 2H, βCH₂), 1.3-1.2 (m, 26H, CH₂), 0.85 (t, 3H, CH₃, J _{CH2, CH3} = 7.0).
13 C-NMR (CH₃Cl): δ = 133.98 (C-2), 126.14 (C-3), 92.89 (C-1), 67.96 (C-4, C-5), 70.46-61.62 (C-6, OCH₂ ), 31.80-22.56 (CH₂), 13.99 (CH₃) ppm.

Example 7 4,6-di-hydroxyl-1- (O-dodecyltricosaoxyethylene) -2,3-dideoxy-hex-2-en-o-pyranoside (3b)

With 3a yield: 1.3 g (88%), yellow syrup, [α] = + 7.6 ° (CHCl₃, c = 0.985), IR (capillary) cm ^-1 :
(C = O) band has disappeared.
C₆₄H₁₂₆O₂₇ (1327.69 g / mol), calc .: C, 57.89; H, 9.56. Found: C, 58.96; H, 9.48. 1 H-NMR (CD₃OD₃): δ = 5.94 ppm (m, 1H, H-2), 5.75 (m, 1H, H-3), 5.00 (m, 1H, H-1), 4.4-3.4 (m, 98H , H-OCH₂, H-6a, 6b, 5, 4, αCH₂), 1.55 (m, 2H, βCH₂), 1.4-1.1 (m, 18H, CH₂), 0.85 (t, 3H, CH₃, J _{CH2, CH3} = 7.0).
13 C-NMR (CH₃Cl): δ = 134.86 (C-2), 127.11 (C-3), 95.73 (C-1), 67.96 (C-4, C-5), 70.46-61.62 (C-6, OCH₂ ), 31.80-22.56 (CH₂), 13.99 (CH₃) ppm.

Example 8 6-hydroxyl-4-O- (2,3,4,6-tetra-hydroxyl-α-D-glucopyranosyl) -1- (O-dodecyltricosaoxy ethylene) -2,3-dideoxy-α-D-erythro-hex-2-eno-pyranoside (4b)

With 4a.
Yield: 1.25 g (56%), yellow syrup, [α] = + 16.1 ° (CHCl₃, c = 0.9), IR (capillary) cm ^-1 :
(C = O) band has disappeared.
C₇₀H₁₃₆O₃₂ (1489.83 g / mol), calc .: C, 56.40; H, 9:20. Found: C, 56.46; H, 8.83.
1 H-NMR (CDCl₃): δ = 5.95 (m, 1H, H2), 5.90 (m, 1H, H-3), 5.45 (m, 2H, H-1, H-3 '), 5.21 (d, 1H , H-1 ′), 5.00 (t∼dd, 1H, H-4 ′), 4.78 (dd, 1H, H-2 ′), 4.25-4.80 (m, 7H, H-6, 6 ′, 5, 4, 5 ′), 3.8-3.4 (m, 94H, H-CH₂), 1.60 (m, 2H, H-CH₂), 1.4-1.3 (18 H, H-CH₂), 0.8 (t, 3H, H- CH₃) ppm.

Example 9

To hydrogenate the double bond, 1.2 mmol of 1a are dissolved in 25 ml of ethanol, 10% Pd / C are added and the mixture is hydrogenated under normal pressure until the starting material has reacted completely. The catalyst is filtered off over silica gel 60 and the solvent is removed on a rotary evaporator. Yield: 930 mg (93%), yellow syrup, [α] = +9.7 (c = 0.99) C₄₂H₈₀O₁₆ (841.09 g / mol), calc .: C , 59.97; H, 9.58. Found: C, 59.18; H, 9.46
1 H-NMR: 6 = 5.17 ppm (m, 1H, H-1), 5.04 (m, 1H, H-4), 4.60 (dd, 1H, H-6a), 4.39 (dd, 1H, H-6b) , 4.33-3.72 (m, 43H, H-OCH₂, 5), 2.39 (s, 3H, H-acetyl), 2.36 (s, 3H, H-acetyl), 2.32- 1.80 (m, 4H, H-2eq, 2ax, 3eq, 3ax), 1.4-1.3 (m, 20H, H-CH₂), 1.20 (t, 3H, H-CH₃), J _5.6a = 5.0, J _5.6b = 2.4, J _{CH2, CH3} = 6.5, J _{6a, 6b} = 12.0 Hz. 13 C-NMR = 170.57 (C = O), 169.73 (C = O), 96.33 (C1), 77.54-61.65 (OCH₂), 67.77, 68.05 (C4, C5) , 31.83-22.59 (CH₂, C2, C3), 20.97, 20.71 (CH₃, CH₃), 14.02 (CH₃).

Examples 10-17 Hydrogenation process

General procedure: The hydrogenation of 1.0 mmol methyl α-acetaminocinnamate is carried out at 25 ° C and 0.1 MPa hydrogen pressure in 15 ml solvent with the addition of 0.01 mmol [Rh (COD) ₂] BF₄ performed. To form the catalyst, the BPPM, the Rhodium complex and the additional amphiphile in an oxygen-free hydrogenation vessel 15 minutes. touched. The hydrogenation is then started. The following examples specified values for t / 2 give the time for the inclusion of half of the theoretical Amount of hydrogen. After the reaction has ended, the mixture is extracted into chloroform and the enantiomeric excess was determined by GC.

The following examples are summarized in a table and were carried out analogously:

Claims (8)

1. Chiral micelle formers of the general formula I in the
R¹ = R² = COAlkyl, COAryl or H or
R¹ = COAlkyl, COAryl or H and
R² = α-D-glucopyranosyl (maltose), β-D-galactopyranosyl (lactose) or β-D-glucopyranosyl (cellobiose) and
n is an integer 4 and
m is an integer 8
represent
and their hydrogenated form of the general formula II with the meanings given above. 2. Process for the preparation of the new chiral micelle formers of the general formula I according to claim 1, characterized in that an acetyl-protected 1,2- Dideoxy sugar with a polyoxyethylene ether in an aprotic polar Solvent in the presence of a Lewis acid at a temperature between -10 and + 50 ° C is implemented. 3. The method according to claim 2, characterized in that as an aprotic polar Acetonitrile solvent is used. 4. The method according to claim 2 and 3, characterized in that as Lewis acid Tin tetrachloride is used. 5. The method according to claim 2 to 4, characterized in that at a temperature of 25 ° C is implemented. 6. Process for the preparation of the hydrogenated form of the general formula II from the chiral prepared according to claim 1 according to a method of claims 2 to 5 Micellogen of the general formula I, characterized in that the chiral Micellogen of the general formula I in a solvent after adding a catalyst is hydrogenated under normal pressure until conversion is complete. 7. The method according to claim 6, characterized in that ethanol as the solvent and Pd / C can be used as a catalyst. 8. Use of the produced by a method according to any one of claims 2 to 7 new micelle formers of general formula I or their hydrogenated form of general formula II according to claim 1 for asymmetric hydrogenations in water as Reaction medium.