Amino acid derivatives suitable as surfactants

Abstract

The present invention relates to the use of amino acid derivatives as surfactants in a surfactant-containing aqueous formulation, characterised in that i) the aqueous formulation as surfactant comprises at least one amino acid derivative of formula (I) wherein R1 is selected from hydrocarbon groups having 4 to 26 carbon atoms, in which optionally at least one carbon atom is replaced by an oxygen or sulfur atom, the R2 and R3 are each independently selected from hydrogen and hydrocarbon groups having 1 to 26 carbon atoms, in which optionally at least one carbon atom atom is replaced by an oxygen or sulfur atom, R5 is selected from divalent hydrocarbon groups having 1 to 6 carbon atoms, in which optionally at least one carbon atom is replaced by an oxygen or nitrogen atom and which are optionally substituted with -OH or -COOH, R4 and R6 are selected from hydrogen and hydrocarbon groups having 1 to 8 carbon atoms, in which optionally at least one carbon atom is replaced by an oxygen or nitrogen atom and which are optionally substituted with -OH or -COOH, wherein R4 and R5 or R4 and R6 are optionally interconnected and together with the nitrogen atom or the carbon atom to which they are bound form a 5- or 6-membered heterocyclic ring, R7 is selected from -OH and an amino group of an α-amino acid or a di- or oligopeptide thereof, in order to form, together with the carbonyl group to which it is bound, the free amino acid or a di-, tri- or higher oligopeptide, or is a sodium or potassium salt thereof, and n = 1, 2 or 3; and ii) the at least one surfactant of formula (I) simultaneously serves as a thickening or gelling agent, wherein the viscosity of the aqueous formulation is adjusted by controlling the pH value and / or the temperature thereof.

Description

[0001] Amino acid derivatives suitable as surfactants

[0002] The present invention relates to amino acid derivatives suitable as surfactants based on phenyl etherified with a fatty alcohol and a process for their production starting from suitable starting materials from renewable raw materials.

[0003] STATE OF THE ART

[0004] The synthesis of diverse chemical compounds from starting materials that are relatively easy and inexpensive to obtain from renewable resources has increased significantly, particularly in the last two decades, against the backdrop of climate change. Research groups worldwide are increasingly focusing their work on developing manufacturing processes based on such starting materials, especially when this approach can yield products that are essential components of everyday goods. These include surfactants, which are indispensable in many cleaning agents and cosmetics, as well as in pharmaceuticals, biochemistry, and the food industry. Various carboxylates and sulfonates, as well as quaternary ammonium salts, polyhydric alcohols, and polyethylene oxide residues, are used as hydrophilic groups in these processes.Amine N-oxides as hydrophilic components of surfactants, however, are hardly represented in the state of the art.

[0005] The working group of the inventors of the present application has also been working for several years on the production of surfactants from starting materials derived from renewable resources, initially focusing on the use of lignin degradation products obtainable by depolymerization. Depending on whether a reductive or an oxidative reaction strategy is chosen, the resulting degradation products are largely phenol and benzaldehyde derivatives, which often each have one or more alkyl and / or alkoxy substituents on the aromatic ring, such as guaiacol and syringol or vanillin and syringaldehyde. For example, in WO 2023 / 046766 A1, the inventors disclose the production of disulfonates suitable as surfactants, for instance, starting from vanillin according to the following reaction scheme:

[0006]

[0007] in which R 1 each represents a residue of a fatty alcohol, X represents a counterion to the sulfonate groups, and the dashed line represents an optional ring closure to form a five- or six-membered ring.

[0008] At the same time, however, the inventors also researched the production of amine N-oxides suitable as surfactants and disclosed their invention in this regard, among other things, in WO 2023 / 046768 A1, whereas previously only a single aromatic amine N-oxide was known as a surfactant in the prior art, namely p-dodecyloxybenzyldimethylamine N-oxide (abbreviated: "pDoAO"):

[0009]

[0010] "pDoAO"

[0011] which can be found in the following three articles: Goracci et al., ChemBioChem 6(1), 197-203 (2005), Cesareti et al., Phys. Chem. Chem. Phys. 17(26), 17214-17220 (2015), and Gabriele et al., Langmuir 34(38), 11510-11517 (2018). A synthesis method for this results from a combination of these disclosures, starting from

[0012]

[0013] In WO 2023 / 046768 A1, however, the inventors disclose an improved and simplified manufacturing process for similar surfactants based on phenol derivatives, which comprises only three reaction steps and enables overall yields of over 90%, using 4-ethylphenol, 4-ethylguaiacol and 4-ethylpyrocatechol as starting materials:

[0014]

[0015] The compounds were in all cases first subjected to an aminoalkylation according to Mannich in the presence of formaldehyde in a polar solvent, whereby one or two hydrogen atoms in the ortho position to a phenolic OH group were each replaced by a dialkylaminomethyl group RR'N-CH2-(n), after which free phenolic OH groups were each etherified according to Williamson with a fatty alcohol residue and finally any amino groups were converted to N-oxides, i.e. the above groups to those of the formula RR'N + (O')-CH2- were oxidized. In some cases, dimers were also produced, in which one of the above groups per molecule was linked to one from another molecule via R and / or R'. As general examples of the end products, only the following two structures are mentioned here:

[0016]

[0017] where R" represents a residue of a fatty alcohol.

[0018] Amino acids substituted with fatty alcohol residues have long been known as surfactants. However, according to the inventors' knowledge, amino acids derived from products of renewable raw materials, and therefore exhibiting corresponding structures, have never before been described in the literature.

[0019] The aim of the invention was therefore to provide suitable amino acid derivatives as surfactants and to produce them from the above starting materials.

[0020] REVELATION OF THE INVENTION

[0021] The present invention achieves this objective in a first aspect by providing the use of amino acid derivatives as surfactants in a surfactant-containing aqueous formulation, characterized in that

[0022] i) the aqueous formulation as surfactant comprises at least one amino acid derivative of the following formula (I):

[0023]

[0024] in which R 1 selected from linear, branched or cyclic hydrocarbon residues with 4 to 26 carbon atoms, in which at least one carbon atom may be replaced by an oxygen or sulfur atom,

[0025] the R 2 and the R 3 each independently selected from hydrogen and linear, branched or cyclic hydrocarbon residues with 1 to 26 carbon atoms, in which at least one carbon atom may be replaced by an oxygen or sulfur atom,

[0026] R 5 selected from divalent hydrocarbon residues with 1 to 6 carbon atoms, in which optionally at least one carbon atom is replaced by an oxygen or nitrogen atom and which optionally are substituted with -OH or -COOH, R 4 and R 6selected from hydrogen and hydrocarbon residues with 1 to 8 carbon atoms, in which optionally at least one carbon atom is replaced by an oxygen or nitrogen atom and which optionally are substituted with -OH or -COOH, wherein R 4 and R 5 or R 4 and R 6 possibly connected to each other and together with the nitrogen atom or the carbon atom to which they are bonded, form a 5- or 6-membered heterocyclic ring,

[0027] R 7 is selected from -OH and an amino residue of an α-amino acid or a di- or oligopeptide thereof, together with the carbonyl group to which it is bonded, to form the free amino acid or a di-, tri- or higher oligopeptide, or stands for a sodium or potassium salt thereof, and

[0028] n = 1, 2 or 3; and (ii) at least one surfactant of formula (I) simultaneously serves as a thickening or gelling agent, wherein the viscosity of the aqueous formulation is adjusted by controlling its pH and / or temperature.

[0029] The inventors surprisingly discovered not only that amino acid derivatives structurally similar to the amine N-oxides cited above are suitable for use as surfactants in aqueous solutions, but also that the above compounds of formula (I) act as thickening or gelling agents, which is not the case for commercially available surfactants, as can be seen from the subsequent comparison between examples according to the invention and comparative examples.

[0030] This means that these compounds are not only amphiphilic substances that reduce the surface tension of liquids and thus act as dispersants or solubilizers, but they also bind a sufficient amount of water and thereby increase the viscosity of an aqueous solution – even to the point of gel formation, sometimes even at an almost neutral physiological pH of a solution with 1 wt%.

[0031] Furthermore, it was found that the viscosity of an aqueous formulation containing a compound of formula (I) can be controlled within relatively narrow limits by adjusting the pH and / or temperature, i.e., it can

[0032] a) by reducing the pH, preferably to a value < 3; or

[0033] b1) reduced by increasing the pH, preferably to a value > 10; and / or

[0034] b2) by increasing the temperature, preferably to a temperature > 45 °C.

[0035] Preferred embodiments of the above use are those in which

[0036] R 1 stands for Ce-C22 alkyl; and / or

[0037] the R 2 each are independently selected from hydrogen, Ci-C22 alkyl and Ci-C22 alkoxy; and / or the R 3 Each is independently selected from hydrogen, methyl, and methoxy. This means that the -NR grouping 4 R 5 -COO- further distant remains R 1 and R 2 preferably also long-chain fatty alcohol residues, which increase the hydrophobicity of the phenyl substituent - especially in embodiments where the residues R 4 to R 7 additional hydrophilic groups, such as NH, OH or COOH or a Na + or K + Salt of it, include. The nearby remains R 3They should, however, be quite short-chain or consist of a single hydrogen atom.

[0038] This further means that in particularly preferred embodiments

[0039] a) a1) R 1 for Cs-C alkyl, more preferably Cw-Cis alkyl, in particular C12-C18 alkyl, and / or a2) the R 2 each are independently selected from hydrogen, Ci-C4-alkyl and Ci-C4-alkoxy and / or a3) the R 3 each are hydrogen; or b) b1) R 1 For Cs-C alkyl, or even more preferably Cw-cis alkyl, in particular C12-C18 alkyl, stands a residue R. 2 for -OR 1 stands, the other remainder R 2 Hydrogen or methoxy is and the R 3 each are hydrogen or b2) R 1 for Cs-cis-alkyl, more preferably Cw-cis-alkyl, in particular Ci2-cis-alkyl, stands the R 2 each are hydrogen or methoxy and the R 3 Each is hydrogen.

[0040] In this way, the above-mentioned degradation products guaiacol and syringol or vanillin and syringaldehyde, as well as 4-ethylphenol, 4-ethylguaiacol and 4-ethylcatechol, which are obtained from lignin by depolymerization, can be used as starting materials for the preparation of the compounds of formula (I).

[0041] Regarding the substituents of the amino acid group -NR 4 R 5 -COO- is concerned, in preferred embodiments these are selected such that

[0042] a) R 5 selected from divalent hydrocarbon residues with 1 to 5 carbon atoms, in which at least one carbon atom may be replaced by an oxygen or nitrogen atom, and R 4 and R 6 each independently selected from methyl, hydroxymethyl, carboxymethyl, 1- or 2-hydroxyethyl and 1- or 2-carboxyethyl or R 4 stands for hydrogen; or

[0043] b) R 4 and R 5 or R4 and R 6 are interconnected alkylene groups which, together with the nitrogen atom or the carbon atom to which they are bonded, form a 5- or 6-membered heterocyclic ring, which may optionally be substituted with -OH or -COOH; or

[0044] c) R 6 comprising a 5- or 6-membered aromatic ring, which may optionally be a benzene or imidazole ring.

[0045] In this way, the hydrophilicity of this end of the amphiphilic molecules is at least not significantly reduced or even increased, and amino acids comprising an alicyclic or heterocyclic ring are also suitable as reactants.

[0046] In particularly preferred embodiments, R 4 , R 5 and R 6 selected so that the grouping R 7 OC-CH2R 5 R 6 -NR 4- in formula (I) for the amino residue, optionally further substituted with -OH or -COOH, of an amino acid selected from glycine, alanine, serine, aspartic acid, proline, pipecolic acid, phenylalanine and histidine, if R 7 for OH, or of a di- or oligopeptide thereof with the α-amino acid or its di- or oligopeptide, as in R 7 defined, stands.

[0047] In other embodiments, R 7 a remainder of the formula -(NR 4 -CHR 5 R 6 -CO) P -OH, wherein R 4 , R 5 and R 6 as defined above and p represents an integer from 0 to 10, where preferably either

[0048] p = 0 such that R 7for OH, and the amino acid derivative of formula (I) is a derivative of an amino acid selected from glycine, alanine, serine, aspartic acid, proline, pipecolic acid, phenylalanine and histidine, optionally further substituted with -OH or -COOH; or

[0049] p = 1 to 10 is the R 4 and the R 5 in formula (I) are each identical and the amino acid derivative of formula (I) comprises a di- or oligopeptide of an amino acid optionally further substituted with -OH or -COOH and selected from glycine, alanine, serine, aspartic acid, proline, pipecolic acid, phenylalanine and histidine, so that short-chain peptides as an alternative to these individual amino acids are also within the scope of protection of the invention.

[0050] In a second aspect, the present invention provides an amino acid derivative of formula (I) for which the same definitions and also the same preferences for the R groups apply. 1 to R 7, n and p are as defined above. In particularly preferred embodiments, the amino acid derivative according to the second aspect is selected from the following compounds:

[0051] N-(4-Dodecyloxy-3-methoxybenzyl)proline (1)

[0052]

[0053] N-(4-Dodecyloxy-3-methoxybenzyl)-4-hydroxyproline (2)

[0054]

[0055] N-(3-(4-Dodecyloxy-3-methoxyphenyl)propyl)proline (4)

[0056]

[0057] N-(4-Dodecyloxybenzyl)proline (7)

[0058]

[0059] N-(4-Dodecyloxybenzyl)-4-hydroxyproline (8)

[0060]

[0061] N-(4-Dodecyloxybenzyl)pipecolic acid (9)

[0062]

[0063] 2,2'-((4-Dodecyloxy-3-methoxybenzyl)azandiyl)diacetic acid (14)

[0064]

[0065] 2,2'-((4-Dodecyloxy-3-methoxybenzyl)azandiyl)diessigsäure-Dinatriumsalz (15)

[0066]

[0067] N-(4-Octyloxy-3-methoxybenzyl)prolin (16)

[0068]

[0069] N-(4-Dodecyloxy-3-methoxyphenethyl)-4-hydroxyprolin (18)

[0070]

[0071] N-(4-Dodecyloxy-3-methoxyphenethyl)piperidin-4-carbonsäure (19)

[0072]

[0073] N-(3-(4-Decyloxy-3-methoxyphenyl)propyl)prolin (21 )

[0074]

[0075] N-(3-(4-Dodecyloxyphenyl)propyl)prolin (22)

[0076]

[0077] N-(4-Dodecyloxy-3-methoxybenzyl)glycin-Natriumsalz (23)

[0078] coo Na +

[0079]

[0080] N-(4-Dodecyloxy-3-methoxybenzyl)alanin-Natriumsalz (24)

[0081]

[0082] N-(4-Dodecyloxy-3-methoxybenzyl)phenylalanin-Natriumsalz (25)

[0083]

[0084] N-(4-Dodecyloxy-3-methoxybenzyl)tyrosin-Natriumsalz (26)

[0085]

[0086] N-(4-Dodecyloxy-3-methoxybenzyl)serin-Natriumsalz (27)

[0087]

[0088] N-(4-Dodecyloxy-3-methoxybenzyl)histidin-Natriumsalz (28)

[0089]

[0090] N-(4-Dodecyloxy-3-methoxybenzyl)-ß-alanin-Natriumsalz (29)

[0091]

[0092] N-(4-Octadecyloxy-3-methoxybenzyl)tyrosin-Natriumsalz (30)

[0093]

[0094] N-(4-Dodecyloxy-3-methoxybenzyl)glycylglycin-Natriumsalz (31 )

[0095]

[0096] And in a third aspect, the present invention also provides a method for producing the above amino acid derivatives according to the second aspect, comprising the following steps:

[0097] 1) the reaction of the free phenolic OH group(s) of a 4-hydroxyalkylphenol derivative of formula (II) below or, in the case of derivatives with n = 1, of a 4-hydroxybenzaldehyde derivative of formula (III) below:

[0098]

[0099] in which the R 3 each independently selected from hydrogen and linear, branched or cyclic hydrocarbon residues with 1 to 26 carbon atoms, in which optionally at least one carbon atom is replaced by an oxygen or sulfur atom, and the R 8 each independently from -OH and the options for R 3 are selected

[0100] with a combination of the formula R 1 -Y, wherein R 1selected from linear, branched or cyclic hydrocarbon residues with 4 to 26 carbon atoms, in which optionally at least one carbon atom is replaced by an oxygen or sulfur atom, and Y represents a leaving group selected from halides and sulfonates, by means of an etherification reaction according to Williamson in the presence of a base in an organic solvent, wherein the compound of formula R 1 -Y is used in an amount of less than 1 equivalent per equivalent of phenolic OH groups of the derivative of formula (II) or (III), giving a corresponding ether of formula (IV) or (V):

[0101]

[0102] in which the R 2 each independently from -OR 1 and the options for R 3 are selected and where in formula (IV) n = 1, 2 or 3; and

[0103] 2a) the direct reaction of the ether of formula (IV) with an amino acid or a di- or oligopeptide thereof or

[0104] 2b) the reduction of the ether of formula (V) to the ether of formula (IV) with n = 1 and its subsequent reaction with an amino acid or a di- or oligopeptide thereof or

[0105] 2c) the direct reaction of the ether of formula (V) with an amino acid or a di- or oligopeptide thereof under a hydrogen atmosphere, each in the presence of a Shvo catalyst, to obtain the corresponding amino acid derivative of formula (I):

[0106]

[0107] in which R 5 selected from divalent hydrocarbon residues with 1 to 6 carbon atoms, in which optionally at least one carbon atom is replaced by an oxygen or nitrogen atom and which optionally are substituted with -OH or -COOH, R 4 and R 6selected from hydrogen and hydrocarbon residues with 1 to 8 carbon atoms, in which optionally at least one carbon atom is replaced by an oxygen or nitrogen atom and which optionally are substituted with -OH or -COOH, wherein R 4 and R 5 or R 4 and R 6 may be linked together and, together with the nitrogen atom or the carbon atom to which they are bonded, form a 5- or 6-membered heterocyclic ring, R 7 from -OH and an amino residue of an α-amino acid or a di- or oligopeptide thereof is selected to form, together with the carbonyl group to which it is bound, the free amino acid or a di-, tri- or higher oligopeptide, and n = 1, 2 or 3.

[0108] In this way, according to the present invention, amino acid derivatives suitable as surfactants and thickening or gelling agents can be synthesized from conventional products of lignin degradation in only two or three (if step 2b) reaction steps.

[0109] This involves significantly fewer synthesis steps than those for the preparation of the amine N-oxide "pDoAO" cited at the beginning, in which a phenolic alcohol group obtained after initial Williamson etherification and reduction must first be converted into the bromide before it can react with an amine (which in this case would correspond to an amino acid). Furthermore, the reaction sequence is, so to speak, "reversed" compared to that used by the inventors for the preparation of amine N-oxides: At that time, starting from 4-ethylphenol, 4-ethylguaiacol, and 4-ethylcatechol, an aminoalkylation according to Mannich was first carried out in the presence of formaldehyde before free phenolic OH groups were etherified. The prior art cited in the introduction therefore cannot suggest the process according to the invention. The exact reaction conditions are not specifically restricted and can depend on the reactants chosen in each individual case, i.e.,of the respective 4-hydroxyalkylphenol or 4-hydroxybenzaldehyde derivative in step 1) and the amino acid or peptide in step 2) are optimized by routine experiments.

[0110] In preferred embodiments of the invention, in step 1)

[0111] Potassium carbonate (K2CO3) is used as a base.

[0112] used as an organic solvent acetonitrile CH3CN and / or

[0113] as a combination of the formula R 1 -Y a bromide or chloride is used;

[0114] where in step 1) even more preferred

[0115] Pre-dried powdered K2CO3 is used as a base,

[0116] is used as an organic solvent, anhydrous CH3CN, and / or as a compound of formula R 1 -Y a bromide is used;

[0117] where in step 1) in particular

[0118] the organic solvent is refluxed and / or

[0119] the connection of the formula R 1 -Y is used in an amount of 0.96 to 0.99 equivalents per equivalent of phenolic OH groups of the derivative of formula (II) or (III).

[0120] In this way, the majority of the compounds of formula (I) according to the invention can be produced in a relatively short time and in high yields.

[0121] For similar reasons, if in step 2) the ether of formula (V) obtained in step 1) from an aldehyde starting material is first reduced to the ether of formula (IV) with n = 1 according to step 2b), which is then reacted with the amino acid or a diode or oligopeptide thereof, the reduction is preferably carried out in the presence of a palladium catalyst under a hydrogen atmosphere.

[0122] Furthermore, the reaction of the ethers of formula (IV) or (V) with the amino acid or a di- or oligopeptide thereof in step 2) is preferably carried out in a protic solvent under reflux, even more preferably under a hydrogen atmosphere, wherein trifluoroethanol is particularly preferably used as the protic solvent. BRIEF DESCRIPTION OF THE DRAWINGS

[0123] The single figure, Fig. 1, shows two photographs of gels produced using surfactants according to the invention, which also act as gelling agents.

[0124] EXAMPLES

[0125] The present invention will be described in more detail below with reference to exemplary embodiments, which are cited solely for the purpose of illustrating the invention and are not to be understood as limiting the scope of protection. Due to the relatively high similarity of the structures and chemical properties of the compounds of formula (I), as well as the starting materials that can be used in the manufacturing process according to the invention and the almost analogous reaction procedure, there will be no doubt among those skilled in the art that the process according to the invention can be carried out with all reactants defined in the accompanying claims and will in any case yield a corresponding amphiphilic amino acid derivative of formula (I) suitable as a surfactant, with one or more amino acid groups in the hydrophilic end.

[0126] Furthermore, relevant experts assume that the vast majority of the amino acid derivatives included in formula (I) will most likely act not only as surfactants but also as thickening or gelling agents in aqueous solutions. The latter, of course, depends on the concentration and thus on the water solubility of the substances, which in turn can be pH-dependent.

[0127] The preparation of the amino acid derivatives used in the embodiments of the present invention according to the process of the invention is described below, with the preparation of the etherified intermediates of formula (IV) or (V) in step 1) being described as synthesis examples, followed by the reactions with the corresponding amino acid in one of steps 2a) to 2d). All intermediates and end products of the syntheses were analyzed and characterized in various ways as follows.

[0128] Materials and processes

[0129] materials

[0130] All starting materials, solvents, the Shvo catalyst, (p-cymene)ruthenium dichloride dimer, [RuCl2(p-cymene)]2, and the ligand bis[(2-diphenylphosphino)phenyl] ether, DPEPhos, were obtained from commercial sources and used without further purification.

[0131] Flash chromatography

[0132] Chromatographic purification was performed on a Biotage® Select instrument with a UV detector using 25 g spheroidal silica gel columns. The following elution pattern was used for the proline-based products: 100% EtOAc (4 column volumes, SV), 100% EtOAc on 100% MeOH (2 SV), 100% MeOH (14 SV); for the remaining products, the following: 100% EtOAc (4 SV), 100% EtOAc on 50:50 EtOAc:MeOH (2 SV), 50:50 EtOAc:MeOH (4 SV), 50:50 EtOAc:MeOH on 100% MeOH (2 SV), 100% MeOH (8 SV).

[0133] NMR spectroscopy

[0134] 1 H-NMR (300 and 500 MHz) and 13 C-NMR spectra (75 and 126 MHz) were recorded using a 300 MHz Bruker NMR spectrometer in CDCI3, CD3OD or D2O as solvent.

[0135] Mass spectrometry

[0136] This included the use of an Agilent Technologies 6230 TOF LC-MS Model G6230B, equipped with an Agilent G1960-80040 vacuum pump (Varian MS 40+) and a G1958-65268 Agilent Dual Jet Stream ESI source.

[0137] Elementary analysis

[0138] This was carried out at TU Graz on the organic elemental analyzer vario MACRO cube. Surface tension

[0139] For this purpose, the compounds were dissolved in ultrapure water at different pH values ​​to obtain a solution with 1 wt%, which was then stored for 12 h at 25 °C, after which the surface tension was determined with a Krüss Force Tensiometer K100 C using a platinum rod PL03.

[0140] viscosity

[0141] For this purpose, 1 wt% of the compounds was dissolved in deionized water, after which the dynamic viscosity was determined by generating a flow curve using the Physica UDS 200 rheometer pair with an MK22 conical probe at 25 °C, a gap of 50 mm, a cone radius of 25 mm, and a cone angle of 1°. For solutions exhibiting non-Newtonian behavior, qo was determined according to the Vinogradov and Malkin method at shear rates from 0.01 to 1000.

[0142] General synthesis procedures

[0143] General Procedure 1): Etherification of phenolic OH groups according to Williamson. The reaction was carried out in a round-bottom flask equipped with a magnetic stir bar, heating bath, thermocouple for temperature control, and reflux condenser. The pre-dried round-bottom flask was charged under an argon atmosphere (to prevent oxidation) with oven-dried K₂CO₃ (2 equiv.), the respective phenol derivative of formula (II) or (III) (1 equiv.), a corresponding 1-bromoalkane (0.96–0.99 equiv. for (II), 0.85 equiv. for (III)), and MeCN as solvent, and the reaction mixture was refluxed. After 48 h of reaction time, it was cooled to room temperature. After removing and washing the stir bar, the mixture was transferred to a rotary evaporator, and the MeCN was removed under vacuum. The crude mixture was dissolved in Et2O / petroleum ether (1:1), washed with water and then with 0.5 M NaOH solution.After drying the organic phase over anhydrous Na₂SO₄, the solvent was removed under vacuum to obtain the pure alkylated product of formula (I), which was then dried under high vacuum. General Procedure 2a): Reaction of alcohols of formula (IV) with amino acids. An oven-dried, evacuated Schlenk flask with a magnetic stir bar was charged with the respective amino acid (1 equiv.), the corresponding etherified alcohol of formula (IV) (2 equiv.), Shvo catalyst, and 2,2,2-trifluoroethanol as solvent. The flask was then sealed, and the mixture was heated to 120 °C in a preheated oil bath for 24 h. Afterward, it was cooled to room temperature and then purified by flash chromatography with ethyl acetate and methanol as eluents to obtain the respective pure amino acid derivative of formula (I), which was dried under high vacuum.

[0144] General Procedure 2b): Reaction of aldehydes of formula (V) with amino acids. First, NaOH was dissolved in MeOH, after which the corresponding amino acid (1 equiv.) was added and stirred until completely dissolved. Then, the corresponding etherified aldehyde of formula (V) (1 equiv.) was added, and the reaction mixture was refluxed for 8 h, after which the solvent was removed using a rotary evaporator. The residue was dissolved in 2,2,2-trifluoroethanol and transferred to a glass insert containing a Shvo catalyst and a magnetic stir bar. The reactions were carried out in an autoclave equipped with a heating block, thermocouple for temperature control, and pressure gauge for pressure control. The autoclave was sealed, purged three times with hydrogen, and then pressurized with hydrogen at a pressure of 10–40 bar, and the reaction mixture was heated to 120 °C for 24 h.The mixture was then cooled to room temperature, transferred to a round-bottom flask and subsequently purified by flash chromatography with EtOAc and MeOH to obtain the respective pure amino acid derivative of formula (I), which was dried under high vacuum.

[0145] General Procedure 2c): Reaction of aldehydes of formula (V) with amino acids. The reactions were carried out in a glass insert of an autoclave equipped with a magnetic stir bar, heating block, thermocouple for temperature control, and pressure gauge for pressure control. The pre-dried glass insert was charged with the respective amino acid, the corresponding etherified aldehyde of formula (V), Shvo catalyst, and 2,2,2-trifluoroethanol as solvent. The autoclave was sealed, purged three times with hydrogen, and then pressurized with hydrogen at 10 bar. The reaction mixture was heated to 120 °C for 24 h. Afterward, the mixture was cooled to room temperature, transferred to a round-bottom flask, and then purified by flash chromatography with EtOAc and MeOH to obtain the respective pure amino acid derivative of formula (I), which was dried under high vacuum.

[0146]

[0147] the formulas (IV) and

[0148]

[0149] Synthesis example 1: Preparation of 4-octyloxy-3-methoxybenzaldehyde (S1)

[0150]

[0151] (SD

[0152] The synthesis was carried out according to general procedure 1 from vanillin (3 g, 19.73 mmol) and 1-bromooctane (3.24 g, 16.77 mmol) in the presence of K₂CO₃ (4.6 g, 33.54 mmol). Yield: 82% (3.63 g) of a white amorphous solid.

[0153] 1 H-NMR (300 MHz, CDCb) ÖH 0.81 -0.93 (m, 3H), 1 .23-1 .39 (m, 8H), 1 .40-1 .56 (m, 2H), 1 .88 (p, J = 6.7 Hz, 2H), 3.92 (s, 3H), 4.09 (t, J = 6.9 Hz, 2H), 6.96 (d, J = 8.1 Hz, 1H), 7.37-7.47 (m, 2H), 9.84 (s, 1H).

[0154] 13 C-NMR (75 MHz, CDCb) öc 14.22, 22.77, 26.01, 29.02, 29.31, 29.43, 31.91, 56.16, 69.31, 109.32, 111.45, 126.97, 129.96, 149.95, 154.32, 191.08.

[0155] HRMS (ESI+, m / z): calc. for [M+H] +265,1804, gef.: 265,1802.

[0156] Elemental analysis for CieH24O3, calc. (%): C 72.69, H 9.15; get: C 72.78, H 8.97.

[0157]

[0158] The synthesis was carried out according to general procedure 1 from vanillin (5 g, 32.88 mmol) and 1-bromododecane (6.974 g, 27.95 mmol) in the presence of K₂CO₃ (7.7 g, 55.9 mmol). Yield: 76% (6.79 g) of a white powder.

[0159] 1 H-NMR (300 MHz, CDCh) ÖH 0.81-0.92 (m, 3H), 1.19-1.39 (m, 16H), 1.40-1.52 (m, 2H), 1.79-1.95 (m, 2H), 3.92 (s, 3H), 4.09 (t, J = 6.9 Hz, 2H), 6.96 (d, J = 8.1 Hz, 1H), 7.37-7.48 (m, 2H), 9.84 (s, 1H).

[0160] 13 C-NMR (75 MHz, CDCh) öc 14.25, 22.82, 26.00, 29.02, 29.47, 29.57, 29.65, 29.67, 29.70, 29.75, 29.77, 56.15, 69.30, 109.27, 111.42, 127.00, 129.33, 149.93, 154.31, 191.09.

[0161] HRMS (ESI+, m / z): calc. for [M+H] + 321,2424, gef. 321,2439.

[0162] Elemental analysis for C20H32O3, calc. (%): C 74.96, H 10.07; found: C 74.50, H 9.53.

[0163] Synthesis example 3: Preparation of 4-octadecyloxy-3-methoxybenzaldehyde (S3)

[0164]

[0165] The synthesis was carried out according to general procedure 1 from vanillin (0.64 g, 4.2 mmol) and 1-bromooctadecane (1.17 g, 3.5 mmol) in the presence of K₂CO₃ (0.97 g, 7.0 mmol). Yield: 98% (1.38 g) of a white powder.

[0166] 1 H-NMR (600 MHz, CDCh) ÖH 0.87 (t, J = 6.9 Hz, 3H), 1.21-1.38 (m, 30H), 1.46 (p, J = 7.6, 7.1 Hz, 2H), 1.87 (p, J = 7.0 Hz, 2H), 3.92 (s, 3H), 4.09 (t, J = 6.8 Hz, 2H), 6.95 (d, J = 8.1 Hz, 1H), 7.37-7.48 (m, 2H), 9.83 (s, 1H).

[0167] 13 C-NMR (151 MHz, CDCh) öc . 14.20, 22.80, 26.00, 29.00, 29.50, 29.60, 29.70, 29.7-29.9 (m), 32.10, 56.10, 69.30, 109.30, 111.50, 127.00, 130.00, 149.90, 154.30, 191.00.

[0168] HRMS (ESI+, m / z): calc. for [M+H]+ 405,3363, gef. 405,3367.

[0169] Elemental analysis for C26H44Ch, cal. (%): C 77.18, H 10.96; found: C 76.92, H 10.94.

[0170] Synthesis example 4: Preparation of 2-(4-decyloxy-3-methoxyphenyl)ethanol (S4)

[0171]

[0172] The synthesis was carried out according to general procedure 1 from homovanillyl alcohol (0.373 g, 2.22 mmol) and 1-bromodecane (0.466 g, 2.11 mmol) in the presence of K₂CO₃ (0.61 g, 4.43 mmol). Yield: 80% (0.52 g) of a white powder. 1 H-NMR (500 MHz, CDCb) ÖH 0.88 (t, J = 7.0 Hz, 3H), 1.20-1.37 (m, 12H), 1.39-1.49 (m, 2H), 1.78-1.90 (m, 2H), 2.80 (t, J = 6.5 Hz, 2H), 3.83 (t, J = 6.5 Hz, 2H), 3.86 (s, 3H), 3.98 (t, J = 6.9 Hz, 2H), 6.73-6.77 (m, 2H, Ar-H), 6.78-6.85 (m, 1H).

[0173] 13C-NMR (125.8 MHz, CDCb) öc 14.24, 22.81, 26.10, 29.35, 29.45, 29.54, 29.68, 29.70, 32.00, 38.89, 56.13, 63.87, 69.31, 112.86, 113.36, 121.11, 131.02, 147.44, 149.62.

[0174] HRMS (ESI+, m / z): calc. for [M+H] + 309,2424, gef. 309,2403.

[0175] Elemental analysis for CigH32O3, cal. (%): C 73.98, H 10.46; found: C 73.90, H 10.15.

[0176] Synthesis example 5: Preparation of 2-(4-dodecyloxy-3-methoxyphenyl)ethanol (S5)

[0177]

[0178] The synthesis was carried out according to general procedure 1 from homovanillyl alcohol (1.0 g, 5.95 mmol) and 1-bromododecane (1.41 g, 5.65 mmol) in the presence of K₂CO₃ (1.56 g, 11.3 mmol). Yield: 76% (1.44 g) of a white powder.

[0179] 1H-NMR (500 MHz, CDCb) ÖH 0,88 (t, J = 6,9 Hz, 3H), 1 ,22-1 ,38 (m, 16H), 1 ,39-1 ,47 (m, 2H), 1 ,78-1 ,90 (m, 2H), 2,81 (t, J = 6,5 Hz, 2H), 3,83 (t, J = 6,5 Hz, 2H), 3,86 (s, 3H), 3,98 (t, J = 6,9 Hz, 2H), 6,73-6,77 (m, 2H), 6,79-6,85 (m, 1H).

[0180] 13 C-NMR (125,8 MHz, CDCb) öc 14,25, 22,82, 26,11 , 29,35, 29,48, 29,55, 29,71 , 29,74, 29,77, 29,80, 32,05, 38,89, 56,13, 63,88, 69,31 , 112,86, 113,36, 121 ,11 , 131 ,02, 147,44, 149,63.

[0181] HRMS (ESI+, m / z): ber. für [M+H] + 337,2737, gef. 337,2722.

[0182] Elementaranalyse für C2iH36O3, ber. (%): C 74,95, H 10,78; gef.: C 74,34, H 10,48.

[0183] Synthesebeispiel 6: Herstellung von 2-(4-Octadecyloxy-3-methoxyphenyl)ethanol (S6)

[0184]

[0185] The synthesis was carried out according to general procedure 1 from homovanillyl alcohol (4.93 g, 29.31 mmol) and 1-bromooctadecane (9.28 g, 27.85 mmol) in the presence of K₂CO₃ (7.70 g, 55.69 mmol). Yield: 60% (7.08 g) of a white powder. 1 H-NMR (300 MHz, CDCb) ÖH 0.83-0.93 (m, 3H), 1.22-1.28 (m, 28H), 1.39-1.50 (m, 2H), 1.83 (p, J = 7.0 Hz, 2H), 2.81 (t, J = 6.5 Hz, 2H), 3.79-3.85 (m, 2H), 3.86 (s, 3H), 3.98 (t, J = 6.9 Hz, 2H), 6.70-6.77 (m, 2H), 6.79-6.85 (m, 1H).

[0186] 13 C-NMR (75.48 MHz, CDCb) öc 14.33, 22.83, 26.10, 29.35, 29.50, 29.55, 29.71, 29.74, 29.80, 29.84, 32.06, 38.88, 56.27, 63.88, 69.27, 112.78, 113.27, 121.09, 130.98, 147.40, 149.58.

[0187] HRMS (ESI+, m / z): calc. for [M+H] + 421,3676, gef. 421,3699.

[0188] Elemental analysis for C27H4sO3, cal. (%): C 77.09, H 11.50; found: C 76.05, H 11.13.

[0189]

[0190] The synthesis was carried out according to general procedure 1 from 4-(3-hydroxypropyl)-2-methoxyphenol (2.82 g, 15.48 mmol) and 1-bromodecane (3.25 g, 14.71 mmol) in the presence of K₂CO₃ (4.07 g, 29.42 mmol). Yield: 71% (3.36 g) of a white powder.

[0191] 1 H-NMR (500 MHz, CDCb) ÖH 0.88 (t, J = 6.9 Hz, 3H), 1.26-1.29 (m, 12H), 1.37-1.49 (m, 2H), 1.76-1.92 (m, 4H), 2.62-2.68 (m, 2H), 3.68 (t, J = 6.4 Hz, 2H), 3.85 (s, 3H), 3.98 (t, J = 6.9 Hz, 2H), 6.67-6.75 (m, 2H), 6.80 (d, J = 7.9 Hz, 1H).

[0192] 13 C-NMR (125.8 MHz, CDCb) öc 14.24, 22.81, 26.11, 29.38, 29.45, 29.55, 29.69, 29.71, 31.83, 32.03, 34.53, 56.11, 62.46, 69.33, 112.39, 113.28, 120.37, 134.55, 146.93, 149.47.

[0193] Elemental analysis for C20H34O3, cal. (%): C 74.49, H 10.63; found: C 73.65, H 10.30.

[0194]

[0195] The synthesis was carried out according to general procedure 1 from 4-(3-hydroxypropyl)-2-methoxyphenol (2.0 g, 10.98 mmol) and 1-bromododecane (2.46 g, 9.88 mmol) in the presence of K₂CO₃ (2.73 g, 19.76 mmol). Yield: 87% (3.01 g) of a white powder. 1 H-NMR (500 MHz, CDCh) ÖH 0.88 (t, J = 6.9 Hz, 3H), 1.24-1.28 (m, 16H), 1.39-1.47 (m, 2H), 1.77-1.87 (m, 4H), 2.62-2.68 (m, 2H), 3.68 (t, J = 6.4 Hz, 2H), 3.85 (s, 3H), 3.98 (t, J = 6.9 Hz, 2H), 6.68-6.75 (m, 2H), 6.80 (d, J = 7.9 Hz, 1H).

[0196] 13 C-NMR (125.8 MHz, CDCb) öc 14.26, 22.83, 26.12, 29.39, 29.49, 29.57, 29.72, 29.74, 29.78, 29.80, 31.84, 32.06, 34.54, 56.12, 62.48, 69.34, 112.40, 113.28, 120.38, 134.55, 146.94, 149.48.

[0197] HRMS (ESI+, m / z): calc. for [M+H] + 351,2894, gef. 351,2871 .

[0198] Elementary analysis for C 22 H3sO3, calc. (%): C 75.38, H 10.93; found: C 74.44, H 10.61.

[0199]

[0200] The synthesis was carried out according to general procedure 1 from 4-(3-hydroxypropyl)phenol (2.5 g, 16.43 mmol) and 1-bromododecane (3.89 g, 15.61 mmol) in the presence of K₂CO₃ (4.31 g, 31.22 mmol). Yield: 86% (4.31 g) of a white powder. 1 H-NMR (500 MHz, CDCh) ÖH 0.89 (t, J = 6.9 Hz, 3H), 1.25-1.29 (m, 16H), 1.40-1.49 (m, 2H), 1.72-1.81 (m, 2H), 1.82-1.91 (m, 2H), 2.61 -2.68 (m, 2H), 3.67 (t, J = 6.4 Hz, 2H), 3.93 (t, J = 6.6 Hz, 2H), 6.82 (d, J = 8.6 Hz, 2H), 7.10 (d, J = 8.6 Hz, 2H).

[0201] 13 C-NMR (125.8 MHz, CDCh) öc 14.26, 22.83, 26.21, 29.48, 29.49, 29.56, 29.73, 29.75, 29.78, 29.81, 31.29, 32.06, 34.59, 62.44, 68.17, 114.59, 129.39, 133.74, 157.52.

[0202] HRMS (ESI+, m / z): calc. for [M+H] + 321,2788, gef. 321,2769.

[0203] Elemental analysis for C2iH36O2, calc. (%): C 78.70, H 11.32; found: C 78.67, H 11.13.

[0204] Synthesis example 10: Preparation of 4-dodecyloxybenzaldehyde (S10)

[0205]

[0206] The synthesis was carried out according to general procedure 1 from 4-hydroxybenzaldehyde (20.02 g, 163.8 mmol) and 1-bromododecane (30.83 g, 139.4 mmol) in the presence of K₂CO₃ (45.34 g, 327.6 mmol). Yield: 85% (34.42 g) of an ivory-colored solid. 1 H-NMR (300 MHz, CDCb) ÖH 0.88 (t, J = 6.9 Hz, 3H), 1 .22-1 .48, (m, 18H), 1 .76-1 .85 (p, J = 6.7, 6.7, 8.0 , 6.6, 2H), 4.03 (t, J = 6.5 Hz, 2H), 6.99 (dd, J = 8.7 Hz, 2H), 7.83 (dd, J = 8.4 Hz, 2H), 9.87 (s, 1H).

[0207] 13 C-NMR (75 MHz, CDCb) öc 14.13, 22.70, 25.96, 29.06, 29.35, 29.56, 29.59, 29.64, 29.66, 31.92, 68.44, 114.75, 129.72, 132.00, 164.28, 190.85.

[0208] Examples 1 to 31 - Preparation of the amino acid derivatives of formula (I)

[0209] Example 1: Preparation of N-(4-dodecyloxy-3-methoxybenzyl)proline (1)

[0210]

[0211] The synthesis was carried out according to general procedure 2c from (S2) (2.0 g, 6.24 mmol) and L-proline (0.575 g, 5.0 mmol) in the presence of the Shvo catalyst (54 mg, 0.05 mmol, 1 mol%). Yield: 62% (1.31 g) of a white powder.

[0212] 1 H-NMR (500 MHz, MeOD) ÖH 0.90 (t, J = 6.9 Hz, 3H), 1.23-1.39 (m, 16H), 1.47 (p, J = 7.2 Hz, 2H), 1.78 (p, J = 6.7 Hz, 2H), 1.87-1.98 (m, 1H), 2.03-2.16 (m, 2H), 2.38-2.49 (m, 1H), 3.14-3.23 (m, 1H), 3.49-3.57 (m, 1H), 3.85-3.88 (m, 4H), 3.99 (t, J = 6.5 Hz, 2H), 4.19 (d, J = 12.8 Hz, 1H), 4.36 (d, J = 12.8 Hz, 1H), 6.95 (d, J = 8.2 Hz, 1H), 7.02 (dd, J = 8.1 , 2.1 Hz, 1H), 7.14 (d, J = 2.0 Hz, 1H).

[0213] 13 C-NMR (125.8 MHz, MeOD) öc 14.45, 23.74, 23.95, 27.15, 29.92, 30.28, 30.48, 30.50, 30.73, 30.76, 30.78, 33.08, 55.12, 56.58, 59.32, 69.58, 70.06, 114.18, 115.13, 124.38, 124.56, 151,11, 151,22, 173.28.

[0214] HRMS (ESI+, m / z): calc. for [M+H] + 420,3108, gef. 420,3167.

[0215] Elemental analysis for C24H41NO4.H2O, cal. (%): C 68.61 , H 9.90, N 3.20; found: C 68.19, H 9.99, N 3.16.

[0216]

[0217] The synthesis was carried out according to general procedure 2c from (S2) (2.0 g, 6.24 mmol) and trans-4-hydroxy-L-proline (0.676 g, 5.0 mmol) in the presence of the Shvo catalyst (54 mg, 0.05 mmol, 1 mol%). Yield: 68% (1.47 g) of a white powder.

[0218] 1 H-NMR (500 MHz, MeOD) ÖH 0.90 (t, J = 6.9 Hz, 3H), 1.23-1.41 (m, 16H), 1.42-1.52 (m, 2H), 1.73-1.83 (m, 2H), 2.02-2.22 (m, 1H), 2.34-2.65 (m, 1H), 3.16-3.30 (m, 1H), 3.62 (dd, J = 12.5, 4.5 Hz, 1H), 3.87 (s, 3H), 3.90-4.02 (m, 2H), 4.11 -4.38 (m, 2H), 4.42-4.55 (m, 2Ho), 6.93-6.98 (m, 1H), 6.99-7.05 (m, 1H), 7.12-7.16 (m, 1H).

[0219] 13C-NMR (125.8 MHz, MeOD) öc 14.44, 23.74, 27.15, 30.28, 30.48, 30.50, 30.73, 30.76, 30.79, 33.08, 39.85, 56.58, 61.70, 69.08, 70.05, 70.72, 114.16, 115.07, 124.32, 124.63, 151.13, 151.27, 173.05. HRMS (ESI+, m / z): calc. for [M+H] + 436,3057, gef. 436,3083.

[0220] Elemental analysis for C25H41NO5.H2O, cal. (%): C 66.19, H 9.55, N 3.09; found: C 66.24, H 9.56, N 3.65.

[0221] Example 3: Preparation of N-(4-dodecyloxy-3-methoxyphenethyl)proline (3)

[0222]

[0223] The synthesis was carried out according to general procedure 2a from (S5) (0.662 g, 1.97 mmol) and L-proline (0.113 g, 0.99 mmol) in the presence of the Shvo catalyst (54 mg, 0.05 mmol, 5 mol%). Yield: 65% (0.501 g) of a white powder.

[0224] 1H-NMR (500 MHz, MeOD) ÖH 0,90 (t, J = 6,9 Hz, 3H), 1 ,24-1 ,39 (m, 16H), 1 ,41-1 ,51 (m, 2H), 1 ,71-1 ,80 (m, 2H), 1 ,88-2,00 (m, 1H), 2,04-2,20 (m, 2H), 2,37-2,48 (m, 1H), 2,89-3,04 (m, 2H), 3,09-3,18 (m, 1H), 3,27-3,37 (m, 1 H), 3,41 -3,52 (m, 1 H), 3,71 -3,79 (m, 1 H), 3,83 (s, 3H), 3,87-3,92 (m, 1 H), 3,95 (t, J = 6,5 Hz, 2H), 6,80 (dd, J = 8,1 , 2,0 Hz, 1 H), 6,84-6,92 (m, 2H).

[0225] 13 C-NMR (125,8 MHz, MeOD) öc 14,45, 23,74, 24,44, 27,14, 30,25, 30,39, 30,48, 30,51 , 30,72, 30,76, 30,78, 32,76, 33,08, 56,03, 56,56, 57,71 , 70,32, 70,84, 114,00, 115,06, 122,18, 130,48, 149,17, 151 ,21 , 173,55.

[0226] HRMS (ESI+, m / z): ber. für [M+H] + 434,3265, gef. 434,3329.

[0227] Elementaranalyse für C 26 H43NO4.0,5H2O, ber. (%): C 70,55, H 10,02, N 3,16; gef.: C 70,68, H 10,04, N 3,20.Beispiel 4: N-(3-(4-Dodecyloxy-3-methoxyphenyl)propyl)prolin (4)

[0228]

[0229] The synthesis was carried out according to general procedure 2a from (S8) (1.2 g, 3.42 mmol) and L-proline (0.198 g, 1.72 mmol) in the presence of the Shvo catalyst (47 mg, 0.043 mmol, 5 mol%). Yield: 87% (0.372 g) of a white powder.

[0230] 1 H-NMR (500 MHz, MeOD) ÖH 0.90 (t, J = 6.8 Hz, 3H), 1.23-1.38 (m, 16H), 1.41-1.51 (m, 2H), 1.71-1.80 (m, 2H), 1.86-2.16 (m, 5H), 2.34-2.46 (m, 1H), 2.64 (t, J = 7.5 Hz, 2H), 3.00-3.14 (m, 2H), 3.17-3.27 (m, 1H), 3.68-3.76 (m, 1H), 3.77-3.85 (m, 4H), 3.94 (t, J = 6.5 Hz, 2H), 6.73 (dd, J = 8.2, 2.1 Hz, 1H), 6.81- 6.87 (m, 2H).

[0231] 13 C-NMR (125.8 MHz, MeOD) öc 14.45, 23.74, 24.43, 27.15, 28.89, 30.34, 30.43, 30.48, 30.53, 30.73, 30.77, 30.79, 33.08, 33.16, 56.13, 56.22, 56.57, 70.44, 70.72, 113.84, 115.11, 121.74, 134.63, 148.56, 151.07, 173.58.

[0232] HRMS (ESI+, m / z): calc. for [M+H] + 448,3421 , gef. 448,3484.

[0233] Elemental analysis for C27H45NO4.H2O, cal. (%): C 69.64, H 10.17, N 3.01 ; found: C 69.56, H 9.93, N 2.94.

[0234] Example 7: N-(4-Dodecyloxybenzyl)proline (7)

[0235]

[0236] The synthesis was carried out according to general procedure 2c from (S10) (0.25 g, 0.86 mmol) and L-proline (0.079 g, 0.69 mmol) in the presence of the Shvo catalyst (7.5 mg, 0.0069 mmol, 2 mol%). Yield: 61% (0.16 g) of a white powder.

[0237] 1 H-NMR (300 MHz, MeOD) ÖH 1.01 (t, J = 6.4 Hz, 3H), 1.33-1.52 (m, 16H), 1.52-1.66 (m, 2H), 1.80-1.94 (m, 2H), 1.96-2.09 (m, 1H), 2.13-2.24 (m, 2H), 2.43-2.64 (m, 1H), 3.22-3.36 (m, 1H), 3.56-3.69 (m, 1H), 3.91-4.03 (m, 1H), 4.08 (t, J = 6.4 Hz, 2H), 4.30 (d, J = 12.7Hz, 1H), 4.49 (d, J = 12.6 Hz, 1H), 7.06 (d, J = 8.0 Hz, 2H), 7.53 (d, J = 8.2 Hz, 2H).

[0238] 13C-NMR (75 MHz, MeOD) ec 14.46, 23.75, 23.88, 27.16, 29.87, 30.32, 30.49, 30.52, 30.72, 30.73, 30.77, 30.79, 33.08, 54.93, 58.87, 69.08, 69.52, 116.00, 123.69, 133.11, 161.71, 173.15. Example 8: N-(4-Dodecyloxybenzyl)-4-hydroxyproline (8)

[0239]

[0240] The synthesis was carried out according to general procedure 2c from (S10) (0.504 g, 1.72 mmol) and trans-4-hydroxy-L-proline (0.201 g, 1.55 mmol) in the presence of the Shvo catalyst (16.9 mg, 0.0155 mmol, 2 mol%). Yield: 75% (0.47 g) of a white powder.

[0241] 1 H-NMR (300 MHz, MeOD) ÖH 0.85-0.95 (m, 3H), 1.21-1.41 (m, 16H), 1.41-1.52 (m, 2H), 1.69-1.83 (m, 2H), 2.02-2.22 (m, 1H), 2.34-2.47 (m, 1H), 3.10-3.24 (m, 2H), 3.57 (dd, J = 12.4, 4.6 Hz, 1H), 3.98 (t, J = 6.4 Hz, 2H), 4.04-4.27 (m, 2H), 4.39-4.54 (m, 1H), 6.91-6.99 (m, 2H), 7.37-7.45 (m, 2H).

[0242]

[0243] The synthesis was carried out according to general procedure 2c from (S10) (0.25 g, 0.86 mmol) and 2-piperidinecarboxylic acid (0.106 g, 0.82 mmol) in the presence of the Shvo catalyst (9 mg, 0.0082 mmol, 2 mol%). Yield: 73% (0.24 g) of a white powder.

[0244] 1 H-NMR (300 MHz, MeOD) ÖH 0.83-0.95 (m, 3H), 1.22-1.40 (m, 16H), 1.41-1.54 (m, 3H), 1.68-1.91 (m, 6H), 2.18-2.32 (m, 1H), 2.81-2.96 (m, 1H), 3.34-3.47 (m, 2H), 3.96-4.10 (m, 3H), 4.49 (d, J = 12.7 Hz, 1H), 6.93-7.02 (m, 2H), 7.39-7.47 (m, 2H).

[0245] Example 11: N-(4-Dodecyloxy-3-methoxybenzyl)piperidine-4-carboxylic acid (11)

[0246]

[0247] The synthesis was carried out according to general procedure 2c from (S2) (2.0 g, 6.24 mmol) and piperidine-4-carboxylic acid (0.645 g, 5.0 mmol) in the presence of the Shvo catalyst (54 mg, 0.05 mmol, 1 mol%). Yield: 59% (1.29 g) of a white powder.

[0248] 1H-NMR (500 MHz, MeOD) OH 0.90 (t, J = 6.9 Hz, 3H), 1 .24-1 .39 (m, 16H), 1 .43-1 .52 (m, 2H), 1 .72-1 .83 (m, 2H), 1 .99-2.09 (m, 2H), 2.29-2.39 (m, 1H), 2.86 (t, J = 11 .2 Hz, 2H), 3.27-3.34 (m, 2H), 3.86 (s, 3H), 4.00 (t, J = 6.5 Hz, 4.08 Hz), 2H), 6.93-7.01 (m, 2H), 7.09 (d, J = 1 .7 Hz, 1 H).

[0249] 13 C-NMR (125.8 MHz, MeOD) occ 14.45, 23.74, 27.14, 27.90, 30.30, 30.48, 30.50, 30.52, 30.73, 30.77, 30.79, 30.28, 3.28, 3.59 56.60, 61 .70, 70.12, 114.21 , 115.71 , 123.92, 125.12, 151 .09, 151 .16, 180.94.

[0250] HRMS (ESI+, m / z): give. for [M+H] + 434.3265, gif. 434.3304.

[0251] Elemental analysis for C25H4iNO5.0.25H2O, ber. (%): C 71 .28, H 10.01 , N 3.20; Fig.: C 71.13, H 10.07, N 3.10.

[0252] Examples 14 and 15: 2,2'-((4-Dodecyloxy-3-methoxybenzyl)azandiyl)diacetic acid (14) and its disodium salt (15)

[0253]

[0254] The synthesis of (15) was carried out according to general procedure 2c from (S2) (1.94 g, 6.05 mmol) and iminodiacetic acid (0.805 g, 6.05 mmol) in the presence of the Shvo catalyst (39.2 mg, 0.064 mmol, 1 mol%) and, in this case, also of DPEPhos (69 mg, 0.128 mmol, 2 mol%) under a hydrogen pressure of 20 bar. A precipitate formed during the reaction, which was filtered off after completion and purified not by flash chromatography, but by washing with MeOH (100 ml) and toluene (100 ml) and subsequent drying under high vacuum. Yield: 59% (1.72 g) of a white powder.

[0255] 1 H-NMR (300 MHz, D2O) ÖH 0.71-0.82 (m, 3H), 1.04-1.35 (m, 18H), 1.54-1.72 (m, 2H), 3.06-3.17 (m, 4H), 3.54-3.61 (m, 2H), 3.72-3.78 (m, 5H), 6.63-6.79 (m, 2H), 6.93-6.99 (m, 1H).

[0256] 13 C-NMR: Due to the poor solubility of the product except in water, no meaningful results could be obtained. 13C-NMR spectrum recorded. HRMS (ESI-, m / z): cal. for [MH]' 436.2704, found 436.2729; cal. for [2M-H]' 873.5481, found 873.5486. Elemental analysis for C24H37NO6Na20.5H2O, cal. (%): C 58.76, H 7.81, N 2.86; found: C 58.47, H 7.70, N 2.92.

[0257] Dissolving the disodium salt (15) in water and adding 0.1 M HCl to pH 2 yielded the free dicarboxylic acid (14). After evaporating the water, this was redissolved in alcohol to remove the NaCl, after which the solvent was evaporated and the pure compound (14) was obtained.

[0258] Example 16: N-(4-Octyloxy-3-methoxybenzyl)proline (16)

[0259]

[0260] The synthesis was carried out according to general procedure 2c from (S1) (2.0 g, 7.57 mmol) and L-proline (0.696 g, 6.05 mmol) in the presence of the Shvo catalyst (33 mg, 0.0303 mmol, 1 mol%). Yield: 78% (1.71 g) of a white powder.

[0261] 1H-NMR (500 MHz, MeOD) OH 0.87-0.94 (m, 3H), 1 .24-1 .42 (m, 8H), 1 .42-1 .52 (m, 2H), 1 .78 (p, J = 6.6 Hz, 2H), 2.03-2.17 (m, 2H), 2.38-2.49 (m, 1H), 3.15-3.25 (m, 1H), 3.50-3.58 (m, 1H), 3.85-3.88 (m, 4H), 3.99 (t, J = 6.5), Hz, J = 2.2, d 12.8 Hz, 1H), 4.36 (d, J = 12.8 Hz, 1H), 6.95 (d, J = 8.2 Hz, 1H), 7.02 (dd, J = 8.2, 2.1 Hz, 1H), 7.14 (d, J = 2.1 Hz, 1H).

[0262] 13 C-NMR (125.8 MHz, MeOD) values ​​of 14.44, 23.71 , 23.96, 27.15, 29.92, 30.28, 30.40, 30.47, 33.00, 55.15, 56.58, 59.33, 7.6.7 70.06, 114.18, 115.13, 124.29, 124.57, 151 .13, 151 .25, 173.19.

[0263] HRMS (ESI+, m / z): give. for [M+H] + 364.2482, gif. 364.2555.

[0264] Elemental Analysis for C2IH 33 NO4.0,2H2O, good. (%): C 68.71 , H 9.17, N 3.82; See: C 68.70, H 9.44, N 3.76.

[0265] Example 17: N-(4-Decyloxy-3-methoxyphenethyl)proline (17)

[0266]

[0267] The synthesis was carried out according to general procedure 2a from (S4) (2.0 g, 6.48 mmol) and L-proline (0.373 g, 3.24 mmol) in the presence of the Shvo catalyst (88 mg, 0.0811 mmol, 5 mol%). Yield: 80% (1.05 g) of a white powder.

[0268] 1 H-NMR (500 MHz, MeOD) ÖH 0.90 (t, J = 6.9 Hz, 3H), 1.23-1.41 (m, 12H), 1.41-1.51 (m, 2H), 1.71-1.80 (m, 2H), 1.88-2.00 (m, 1H), 2.04-2.21 (m, 2H), 2.37-2.49 (m, 1H), 2.90-3.05 (m, 2H), 3.10-3.19 (m, 1H), 3.28-3.37 (m, 1H), 3.43-3.53 (m, 1H), 3.72-3.81 (m, 1H), 3.83 (s, 3H), 3.88-3.98 (m, 3H), 6.79 (dd, J = 8.1 , 2.0 Hz, 1H), 6.84-6.91 (m, 2H).

[0269] 13 C-NMR (125.8 MHz, MeOD) öc 14.45, 23.73, 24.46, 27.14, 30.24, 30.39, 30.45, 30.51, 30.69, 30.73, 32.70, 33.07, 56.07, 56.56, 57.72, 70.30, 70.83, 114.00, 115.05, 122.18, 130.39, 149.19, 151,21, 173.42.

[0270] HRMS (ESI+, m / z): calc. for [M+H] + 406,2952, gef. 406,2997.

[0271] Elementary analysis for C 24 H39NO4.0.5H2O, calc. (%): C 68.53, H 9.72, N 3.38; found: C 69.23, H 9.79, N 3.27.

[0272] Example 18: N-(4-Dodecyloxy-3-methoxyphenethyl)-4-hydroxyproline (18)

[0273]

[0274] The synthesis was carried out according to general procedure 2a from (S5) (1.0 g, 2.97 mmol) and trans-4-hydroxy-L-proline (0.195 g, 1.49 mmol) in the presence of the Shvo catalyst (40 mg, 0.037 mmol, 5 mol%). Yield: 74% (0.495 g) of a white powder.

[0275] 1 H-NMR (500 MHz, MeOD) ÖH 0.90 (t, J = 6.9 Hz, 3H), 1.23-1.40 (m, 16H), 1.41-1.51 (m, 2H), 1.71-1.80 (m, 2H), 2.10-2.20 (m, 1H), 2.40-2.49 (m, 1H), 2.91-3.05 (m, 2H), 3.16-3.23 (m, 1H), 3.37-3.46 (m, 1H), 3.54-3.63 (m, 1H), 3.78-3.85 (m, 4H), 3.94 (t, J = 6.5 Hz, 2H), 4.16-4.23 (m, 1H), 4.47-4.53 (m, 1H), 6.79 (dd, J = 8.2, 2.0 Hz, 1H), 6.83-6.92 (m, 2H).

[0276] 13C-NMR (125.8 MHz, MeOD) öc 14.45, 23.74, 27.15, 30.40, 30.48, 30.52, 30.73, 30.76, 30.78, 32.71, 33.08, 39.95, 56.56, 60.06, 62.72, 70.30, 70.43, 70.81, 114.01, 115.04, 122.20, 130.29, 149.19, 151.20, 173.20.

[0277] HRMS (ESI+, m / z): calc. for [M+H] + 450.3214, gef. 450.3243.

[0278] Elementary analysis for C 26 H₃NO₅₀₅H₂O, calc. (%): C 68.09, H 9.67, N 3.05; found: C 68.25, H 9.47, N 3.04. Example 19: N-(4-Dodecyloxy-3-methoxyphenethyl)piperidine-4-carboxylic acid (19)

[0279]

[0280] The synthesis was carried out according to general procedure 2a from (S5) (2.0 g, 5.94 mmol) and piperidine-4-carboxylic acid (0.384 g, 2.97 mmol) in the presence of the Shvo catalyst (81 mg, 0.074 mmol, 5 mol%). Yield: 72% (0.958 g) of a white powder.

[0281] 1H-NMR (500 MHz, MeOD) OH 0.90 (t, J = 6.8 Hz, 3H), 1 .24-1 .41 (m, 16H), 1 .42-1 .50 (m, 2H), 1 .76 (p, J = 6.7 Hz, 2H), 2H), 2.03–2.14 (m, 2H), 2.33–2.43 (m, 1H), 2.93–3.04 (m, 4H), 3.18–3.28 (m, 2H), 3.45–3.51 (m, 2H), 3.84 (s, 3.3H), (s, 3.6, t = 6,6 2H), 6.80 (dd, J = 8.2, 2.1 Hz, 1H), 6.86-6.92 (m, 2H).

[0282] 13 C-NMR (125.8 MHz, MeOD) values ​​of 14.44, 23.74, 27.14, 27.99, 30.39, 30.47, 30.50, 30.72, 30.76, 30.77, 31 ,26, 3.49, 3.49 56.60, 59.34, 70.36, 114.08, 115.13, 122.20, 130.82, 149.17, 151 .24, 180.82. HRMS (ESI+, m / z): give. for [M+H] + 448.3421 , gif. 448.3465.

[0283] Elemental analysis for C 27 H45NO4.0.5H2O, good. (%): C 71 .01 , H 10.15, N 3.07; gif.: C 71.03, H 10.38, N 3.77.

[0284] Example 20: N-(4-Octadecyloxy-3-methoxyphenethyl)proline (20)

[0285]

[0286] The synthesis was carried out according to general procedure 2a from (S6) (2.5 g, 5.94 mmol) and L-proline (0.342 g, 2.97 mmol) in the presence of the Shvo catalyst (81 mg, 0.074 mmol, 5 mol%). Yield: 89% (1.37 g) of a white powder.

[0287] 1 H-NMR (300 MHz, MeOD) ÖH 0.90 (t, J = 6.5 Hz, 1 H), 1.20-1.40 (m, 28H), 1.43-1.49 (m, 2H), 1.69-1.84 (m, 2H), 1.89-2.01 (m, 1H), 2.05-2.19 (m, 2H), 2.33-2.52 (m, 1H), 2.90-3.03 (m, 2H), 3.06-3.18 (m, 2H), 3.40-3.56 (m, 1H), 3.67-3.78 (m, 1H), 3.84 (s, 3H), 3.87-4.01 (m, 3H), 6.74-6.83 (m, 1H), 6.84-6.94 (m, 2H). 13 C-NMR: Due to the poor solubility of the product, no meaningful results could be obtained. 13 C-NMR spectrum will be recorded.

[0288] HRMS (ESI+, m / z): calc. for [M+H] + 518.4204, gef. 518.4264.

[0289] Elemental analysis for C33H55NO4.2H2O, calc. (%): C 69.40, H 10.74, N 2.53; found: C 69.40, H 10.85, N 2.53.

[0290] Example 21: N-(3-(4-Decyloxy-3-methoxyphenyl)propyl)proline (21)

[0291]

[0292] The synthesis was carried out according to general procedure 2a from (S7) (2.0 g, 6.20 mmol) and L-proline (0.357 g, 3.10 mmol) in the presence of the Shvo catalyst (85 mg, 0.078 mmol, 5 mol%). Yield: 63% (0.82 g) of a white powder.

[0293] 1 H-NMR (500 MHz, MeOD) ÖH 0.90 (t, J = 6.9 Hz, 3H), 1.23-1.41 (m, 12H), 1.41-1.51 (m, 2H), 1.70-1.80 (m, 2H), 1.86-2.16 (m, 5H), 2.35-2.46 (m, 1H), 2.64 (t, J = 7.5 Hz, 2H), 3.01-3.15 (m, 2H), 3.18-3.27 (m, 1H), 3.69-3.77 (m, 1H), 3.79-3.85 (m, 4H), 3.94 (t, J = 6.5 Hz, 2H), 6.73 (dd, J = 8.1 , 2.1 Hz, 1H), 6.81- 6.87 (m, 2H).

[0294] 13 C-NMR (125.8 MHz, MeOD) öc 14.45, 23.74, 24.44, 27.15, 28.86, 30.34, 30.43, 30.46, 30.52, 30.70, 30.74, 33.07, 33.13, 56.16, 56.24, 56.57, 70.43, 70.72, 113.84, 115.10, 121.74, 134.60, 148.56, 151.07, 173.46.

[0295] HRMS (ESI+, m / z): calc. for [M+H] + 420,3108, gef. 420,3150.

[0296] Elementary analysis for C 25 H4iNO4.0.25H2O, calc. (%): C 70.80, H 9.86, N 3.30; get: C 70.38, H 9.93, N 3.25.

[0297] Example 22: N-(3-(4-Dodecyloxyphenyl)propyl)proline (22)

[0298]

[0299] The synthesis was carried out according to general procedure 2a from (S9) (2.0 g, 6.24 mmol) and L-proline (0.359 g, 3.12 mmol) in the presence of the Shvo catalyst (85 mg, 0.078 mmol, 5 mol%). Yield: 88% (1.15 g) of a white powder.

[0300] 1 H-NMR (500 MHz, MeOD) ÖH 0.90 (t, J = 6.9 Hz, 3H), 1.23-1.41 (m, 16H), 1.42-1.49 (m, 2H), 1.69-1.79 (m, 2H), 1.85-2.16 (m, 5H), 2.34-2.46 (m, 1H), 2.63 (t, J = 7.5 Hz, 2H), 3.00-3.14 (m, 2H), 3.22 (ddd, J = 12.4, 9.8, 6.3 Hz, 1H), 3.68-3.76 (m, 1H), 3.81 (dd, J = 9.4, 6.1 Hz, 1H), 3.92 (t, J = 6.4 Hz, 2H), 6.79-6.85 (m, 2H), 7.07-7.14 (m, 2H).

[0301] 13 C-NMR (125.8 MHz, MeOD) öc 14.45, 23.74, 24.42, 27.19, 28.96, 30.33, 30.45, 30.48, 30.53, 30.73, 30.76, 30.78, 32.71 , 33.08, 56.12, 56.23, 68.99, 70.71, 115.66, 130.34, 133.40, 159.18, 173.46.

[0302] HRMS (ESI+, m / z): calc. for [M+H] + 418,3316, gef. 418,3354.

[0303] Elemental analysis for C26H43NO3, calc. (%): C 74.77, H 10.38, N 3.35; found: C 74.17, H 10.38, N 3.27.

[0304] Example 23: N-(4-Dodecyloxy-3-methoxybenzyl)glycine sodium salt (23)

[0305]

[0306] The synthesis was carried out according to general procedure 2b from (S2) (1.78 g, 5.55 mmol) and glycine (0.417 g, 5.55 mmol) in the presence of the Shvo catalyst (60 mg, 0.0555 mmol, 2 mol%). Yield: 65% (1.38 g) of a white powder.

[0307] 1H-NMR (300 MHz, MeOD) ÖH 0.84-0.95 (m, 3H), 1.23-1.39 (m, 16H), 1.41-1.53 ​​(m, 2H), 1.69-1.87 (m, 2H), 3.15 (s, 2H), 3.66 (s, 2H), 3.84 (s, 3H), 3.97 (t, J = 6.5 Hz, 2H), 6.81-6.89 (m, 2H), 6.97-7.03 (m, 1H).

[0308] 13 C-NMR (75.48 MHz, MeOD) öc 14.48, 23.75, 27.14, 30.38, 30.49, 30.54, 30.74, 30.78, 30.80, 33.09, 53.28, 54.04, 56.50, 70.33, 113.86, 114.61, 122.20, 133.60, 149.07, 150.88, 178.86.

[0309] HRMS (ESI+, m / z): ber. for [2M+H] + 759.5518, gef. 759.5537.

[0310] Elementar analysis for C22H36NO4Na, ber. (%): C 65,81, H 9,04, N 3,49; gef.: C 66,19, H 9,56, N 3,39. Beispiel 24: N-(4-Dodecyloxy-3-methoxybenzyl)alanin-Natriumsalz (24)

[0311]

[0312] The synthesis was carried out according to general procedure 2b from (S2) (1.97 g, 6.15 mmol) and alanine (0.548 g, 6.15 mmol) in the presence of the Shvo catalyst (67 mg, 0.0615 mmol, 2 mol%). Yield: 56% (1.37 g) of a white powder.

[0313] 1 H-NMR (300 MHz, MeOD) ÖH 0.84-0.95 (m, 3H), 1.19-1.38 (m, 19H), 1.42-1.53 ​​(m, 2H), 1.69-1.84 (m, 2H), 3.05-3.32 (m, 1H), 3.54 (d, J = 12.1 Hz, 1H), 3.70 (d, J = 12.1 Hz, 1H), 3.85 (s, 3H), 3.97 (t, J = 6.5 Hz, 2H), 6.81-6.90 (m, 2H), 6.99-7.05 (m, 1H).

[0314] 13 C-NMR (75.48 MHz, MeOD) öc 14.47, 19.56, 23.74, 27.13, 30.34, 30.37, 30.40, 30.49, 30.53, 30.73, 30.77, 33.08, 52.88, 56.55, 59.78, 70.33, 113.96, 114.62, 122.25, 133.78, 149.01, 150.84, 182.81. HRMS (ESI+, m / z): cal. for [M+H] + 394,2952, gef. 394,2967.

[0315] Elemental analysis for C23H38NO4Na, cal. (%): C 66.48, H 9.22, N 3.37; found: C 66.27, H 9.60, N 3.58.

[0316]

[0317] The synthesis was carried out according to general procedure 2b from (S2) (1.91 g, 5.95 mmol) and phenylalanine (0.983 g, 5.95 mmol) in the presence of the Shvo catalyst (65 mg, 0.0595 mmol, 2 mol%). Yield: 36% (1.02 g) of a white powder.

[0318] 1 H-NMR (300 MHz, MeOD) ÖH 0.83-0.93 (m, 3H), 1.20-1.38 (m, 16H), 1.40-1.50 (m, 2H), 1.67-1.82 (m, 2H), 2.82 (dd, J = 13.4, 7.5 Hz, 1H), 3.00 (dd, J = 13.4, 6.2 Hz, 1H), 3.26-3.37 (m, 1H), 3.47 (d, J = 12.6 Hz, 1H), 3.68 (d, J = 12.6 Hz, 1H), 3.76 (s, 3H), 3.94 (t, J = 6.5Hz, 2H), 6.67-6.89 (m, 3H), 7.09-7.30 (m, 5H). 13 C-NMR (75.48 MHz, MeOD) öc 14.48, 23.75, 27.12, 30.49, 30.53, 30.74, 30.77, 33.08, 41,12, 52.81, 56.34, 66.10, 70.33, 113.67, 114.54, 122.05, 127.15, 129.18, 130.47, 134.02, 140.44, 148.83, 150.76, 181.35.

[0319] HRMS (ESI+, m / z): calc. for [M+H] + 470,3265, gef. 470,3287.

[0320] Elemental analysis for C29H 42NO4Na, calc. (%): C 70.85, H 8.61, N 2.85; found: C 70.16, H 9.08, N 2.79.

[0321] Example 26: N-(4-Dodecyloxy-3-methoxybenzyl)tyrosine sodium salt (26)

[0322]

[0323] The synthesis was carried out according to general procedure 2b from (S2) (1.58 g, 4.93 mmol) and tyrosine (0.893 g, 4.93 mmol) in the presence of the Shvo catalyst (54 mg, 0.0493 mmol, 2 mol%). Yield: 56% (1.34 g) of a white powder.

[0324] 1 H-NMR (300 MHz, MeOD) ÖH 0.84-0.95 (m, 3H), 1.21-1.38 (m, 16H), 1.40-1.51 (m, 2H), 1.75 (p, J = 6.7 Hz, 2H), 2.72 (dd, J = 13.5, 7.5 Hz, 1H), 2.91 (dd, J = 13.5, 6.1 Hz, 1H), 3.21-3.31 (m, 1H), 3.47 (d, J = 12.6 Hz, 1H), 3.69 (d, J = 12.6 Hz, 1H), 3.78 (s, 3H), 3.95 (t, J = 6.5Hz, 2H), 6.61-6.68 (m, 2H), 6.70-6.87 (m, 3H), 6.97-7.12 (m, 2H).

[0325] 13C-NMR (125.8 MHz, MeOD) öc 14.46, 23.73, 27.11, 30.37, 30.39, 30.47, 30.52, 30.72, 30.75, 30.77, 33.07, 39.08, 52.76, 56.56, 66.31, 70.42, 113.72, 114.65, 119.36, 122.00, 124.99, 130.92, 134.19, 148.68, 150.74, 165.62, 180.07.

[0326] HRMS (ESI+, m / z): calc. for [M+H] + 486,3214, gef. 486,3233.

[0327] Elemental analysis for C29H 42 NO5Na, calc. (%): C 68.61, H 8.34, N 2.76; found: C 69.00, H 8.87, N 2.73.

[0328] Example 27: N-(4-Dodecyloxy-3-methoxybenzyl)serine sodium salt (27)

[0329]

[0330] The synthesis was carried out according to general procedure 2b from (S2) (1.79 g, 5.6 mmol) and serine (0.589 g, 5.6 mmol) in the presence of the Shvo catalyst (61 mg, 0.056 mmol, 2 mol%). Yield: 50% (1.16 g) of a white powder.

[0331] 1H-NMR (300 MHz, MeOD) OH 0.83-0.95 (m, 3H), 1 .24-1 .39 (m, 16H), 1 .40-1 .52 (m, 2H), 1 .68-1 .84 (m, 2H), t 3.62 (d, J = 12.5 Hz, 1H), 3.69-3.74 (m, 2H), 3.78 (d, J = 12.5 Hz, 1H), 3.85 (s, 3H), 3.96 (t, J = 6.5 Hz, 2H), 6.8-1 (m, 2H), 7.00-7.06 (m, 1H).

[0332] 13 C-NMR (75.48 MHz, MeOD) values ​​of 14.49, 23.75, 27.14, 30.38, 30.49, 30.54, 30.74, 30.78, 30.80, 33.09, 52.96, 5,6.7, 65.65, 70.34, 113.91 , 114.63, 122.17, 134.05, 148.98, 150.86, 179.94.

[0333] HRMS (ESI+, m / z): give. for [M+H] + 410,2901 , gif. 410.2911 .

[0334] Elemental analysis for C23H38NO5Na.2H2O, gives. (%): C 59.08, H 9.05, N 3.00; fig.: C 58.42, H 8.68, N 3.41.

[0335] Example 28: N-(4-Dodecyloxy-3-methoxybenzyl)histidine-Sodium Salt (28)

[0336]

[0337] The synthesis was carried out according to general procedure 2b from (S2) (2.19 g, 6.83 mmol) and histidine (1.06 g, 6.83 mmol) in the presence of the Shvo catalyst (74 mg, 0.0683 mmol, 2 mol%). Yield: 71% (2.22 g) of a brown solid.

[0338] 1 H-NMR (300 MHz, MeOD) ÖH 0.84-0.94 (m, 3H), 1.22-1.38 (m, 16H), 1.41-1.52 (m, 2H), 1.65-1.83 (m, 2H), 2.69-3.05 (m, 2H, 3.44-3.84 (m, 6H), 3.95 (t, J = 6.6 Hz, 2H), 6.62-6.95 (m, 4H), 7.42-7.55 (m, 1H).

[0339] 13 C-NMR (75.48 MHz, MeOD) öc 14.50, 23.76, 27.14, 30.38, 30.50, 30.55, 30.58, 30.75, 30.78, 30.80, 31.57, 33.10, 52.85, 56.47, 64.47, 70.36, 113.81, 114.59, 121.11, 122.11, 133.95, 134.13, 135.93, 148.90, 150.81, 181.32.

[0340] HRMS (ESI+, m / z): calc. for [M+H] + 460,3170, gef. 460,3186.

[0341] Elemental analysis for C26H4oN304Na.O,5H20, calc. (%): C 63.65, H 8.42, N 8.56; found: C 63.50, H 8.82, N 7.41. Example 29: N-(4-Dodecyloxy-3-methoxybenzyl)-β-alanine sodium salt (29)

[0342]

[0343] The synthesis was carried out according to general procedure 2b from (S2) (1.81 g, 5.65 mmol) and β-alanine (0.503 g, 5.65 mmol) in the presence of the Shvo catalyst (61.5 mg, 0.0565 mmol, 2 mol%). Yield: 52% (1.13 g) of a white powder.

[0344] 1 H-NMR (300 MHz, MeOD) ÖH 0.84-0.98 (m, 3H), 1.23-1.39 (m, 16H), 1.41-1.53 ​​(m, 2H), 1.68-1.84 (m, 2H), 2.41 (t, J = 6.9 Hz, 2H), 2.80 (t, J = 6.8 Hz, 2H), 3.68 (s, 2H), 3.84 (s, 3H), 3.96 (t, J = 6.5 Hz, 2H), 6.83-6.89 (m, 2H), 6.93-7.05 (m, 1H).

[0345] 13 C-NMR (75.48 MHz, MeOD) öc 14.49, 23.76, 27.14, 30.38, 30.50, 30.54, 30.74, 30.78, 30.80, 33.09, 38.19, 46.97, 54.19, 56.51 , 70.34, 113.80, 114.61 , 122.12, 133.72, 149.00, 150.87, 180.84.

[0346] HRMS (ESI+, m / z): calc. for [M+H] + 394,2952, gef. 394,2969.

[0347] Elemental analysis for C23H38NO4Na.2H2O, calc. (%): C 61.17, H 9.38, N 3.10; found: C 61.65, H 9.53, N 3.29.

[0348] Example 30: N-(4-Octadecyloxy-3-methoxybenzyl)tyrosine sodium salt (30)

[0349]

[0350] The synthesis was carried out according to general procedure 2b from (S3) (2.4 g, 5.94 mmol) and tyrosine (1.08 g, 5.94 mmol) in the presence of the Shvo catalyst (64 mg, 0.0594 mmol, 2 mol%). Yield: 47% (1.63 g) of a white powder.

[0351] 1 H-NMR (300 MHz, MeOD) ÖH 0.84-0.95 (m, 3H), 1.24-1.38 (m, 28H), 1.40-1.52 (m, 2H), 1.68-1.84 (m, 2H), 2.60-2.99 (m, 2H), 3.20-3.31 (m, 1H), 3.47 (d, J = 12.7 Hz, 1H), 3.68 (d, J = 12.7 Hz, 1H), 3.80 (s, 3H), 3.88-4.01 (m, 2H), 6.48-6.62 (m, 2H), 6.68-6.97 (m, 5H).

[0352] 13C-NMR (125.8 MHz, MeOD) öc 14.48, 23.75, 27.13, 30.38, 30.49, 30.55, 30.74, 30.77, 30.79, 33.08, 40.25, 52.76, 56.52, 66.31, 70.37, 113.68, 114.59, 119.69, 122.00, 124.89, 131.03, 134.15, 148.78, 150.77, 166.42, 181.81 HRMS (ESI+, m / z): cal. for [M+H] + 570.4153, gef. 570.4185.

[0353] Elemental analysis for C35H54NO5Na.H2O, cal. (%): C 68.94, H 9.26, N 2.30; found: C 67.90, H 8.00, N 2.33.

[0354] Example 31: N-(4-Dodecyloxy-3-methoxybenzyl)qlvcylqlycine sodium salt (31)

[0355]

[0356] The synthesis was carried out according to general procedure 2b from (S2) (2.19 g, 6.83 mmol) and diglycine (0.902 g, 6.83 mmol) in the presence of the Shvo catalyst (74 mg, 0.0683 mmol, 2 mol%). Yield: 51% (1.52 g) of a white powder.

[0357] 1H-NMR (300 MHz, MeOD) ÖH 0.84-0.95 (m, 3H), 1.23-1.39 (m, 16H), 1.41-1.51 (m, 2H), 1.69-1.84 (m, 2H), 3.25 (s, 2H), 3.68 (s, 2H), 3.76 (s, 2H), 3.84 (s, 3H), 3.96 (t, J = 6.6 Hz, 2H), 6.83-6.90 (m, 2H), 6.96-7.04 (m, 1H).

[0358] 13 C-NMR (75.48 MHz, MeOD) öc 14.48, 23.75, 27.14, 30.39, 30.50, 30.54, 30.74, 30.78, 30.80, 33.09, 44.31, 52.00, 54.07, 56.55, 70.34, 113.73, 114.59, 122.08, 122.19, 133.80, 149.08, 150.92, 173.89, 176.40.

[0359] HRMS (ESI+, m / z): calc. for [M+H] + 437,3010, gef. 437,3024.

[0360] Elemental analysis for C24H39N2O5Na.2H2O, cal. (%): C 58.28, H 8.76, N 5.66; found: 58.59, H 8.68, N 5.23.

[0361] Measurements of the surface tension of aqueous solutions of the surfactants according to the invention

[0362] As described above, the compounds were dissolved in ultrapure water. In some cases, the pH had to be adjusted to 12 by adding 1 M NaOH or to 5.9 by adding 1 M HCl, in order to prepare a 1 wt% solution. After 12 h of storage at 25 °C, the surface tension was measured using a Krüss K100 C force tensiometer. The value for pure water at 25 °C was approximately 72 mN / m. The results are given in Table 1 below.

[0363] Table 1: Surface tension of aqueous solutions with 1 wt.%

[0364]

[0365] It can be seen that all of the tested compounds according to the invention, which are representative of different substitution patterns of the compounds of formula (I), were able to reduce the surface tension of aqueous solutions to less than half the value of pure water, which clearly demonstrates the suitability of the compounds of formula (I) as surfactants - especially since even a significantly lower degree of surface tension reduction is sufficient to classify a substance as a surfactant.

[0366] Measurements of the viscosity of aqueous solutions of the inventive surfactants

[0367] As described above, the dynamic viscosity of solutions of the compounds in deionized water with 1 wt% was determined by generating a flow curve using a pair of Physica UDS 200 rheometers (MK 22 conical probe, 25 °C, gap 50 mm, cone radius 25 mm, cone angle 1°). For those solutions exhibiting non-Newtonian behavior, q0 was determined according to the method of Vinogradov and Malkin at shear rates from 0.01 to 1000. For comparison purposes, the viscosity of pure water and of solutions (1 wt%) of the known surfactants laurylamine N-oxide (V1), sodium lauryl sulfate (V2), 3-(N,N-dimethylmyristylammonio)propanesulfonate (a zwitterionic surfactant; V3), and sodium lauroylsarcosinate (an amino acid derivative as a surfactant; V4) was also determined. The results, along with an indication of whether the solutions exhibited Newtonian (N) or non-Newtonian (NN) flow behavior, are given in Table 2 below.

[0368] Table 2: Viscosity of aqueous solutions with 1 wt.%

[0369]

[0370] The results show that all tested compounds according to the invention, with the exception of compound (16), exhibited non-Newtonian flow behavior, which, however, was not the case for any of the commercially available surfactants – not even for the amino acid derivative V4, sodium lauroyl sarcosinate. Compound (17), which has a residue R that is two CH2 groups longer than compound (16). 1 Compound (21), which has one more CH2 group between the nitrogen atom and the phenyl group (n = 2), did, however, exhibit non-Newtonian flow behavior and increased the viscosity more than fourfold. Compound (21), with n = 3, but otherwise the same substitution pattern as compound (17), increased the viscosity 25-fold. Compound (22), with two more CH2 groups in R 1 , but without the methoxy substituent R 2of compound (21 ) yielded more than 700 times the effect, and compound (4) with this methoxy substituent R 2 even 7,000 times that amount.

[0371] For all tested compounds except (16), their suitability as thickeners was thus demonstrated, with those having a q-value above 10 2Furthermore, gels formed when delivered. Photographs of a representative example are shown in the single figure, Fig. 1. This gel formed using 5 wt% of compound (1), which had yielded a q-value 2,000 times higher. This gel was self-supporting and stable (see the photograph in Fig. 1A) and exhibited self-healing properties after a pinprick, i.e., it contracted back into a stable body after only a small loss of water. Moreover, two such gels fused into a single unit as soon as they were brought into contact with each other (see the photograph in Fig. 1B). Because these gels have physiological pH values ​​and aqueous solutions can be injected into them, they are quite suitable for medical applications, for example, for drug delivery.

[0372] From the above interpretation of the measurement results, it follows for a person skilled in the art that the number of carbon atoms in the residues R 1 to R 3 apparently the amount should be at least 10 so that the surfactants according to the invention, in a solution with only 1 wt%, are simultaneously able to serve as thickening or gelling agents - at least in those cases where the nitrogen atom is part of one of the residues R 4 , R 5 and R 6 formed ring and no linear substituent R 4 with more than two or three carbon atoms.

[0373] The same applies to the number of carbon atoms in the R groups. 1 to R 3 probably also for surfactants of formula (I) with more hydrophilic substituents, e.g. heteroatoms instead of carbon atoms, in the R groups 4 to R 6 , especially of course for those with more than one carboxyl group.

[0374] It should be noted, however, that the viscosity is strongly dependent on the temperature of the solution and the concentration of the dissolved surfactants, the latter being also pH-dependent, which allows for the aforementioned control of the viscosity by adjusting optimal pH values ​​and / or temperatures. Consequently, it can be assumed with near certainty by the person skilled in the art that compound (16) and similar surfactants of the invention of formula (I) with shorter R groups also have the same properties. 1 Decyl, in higher concentrations, will indeed be effective as a thickening or gelling agent.

[0375] Further syntheses of compounds of formula (I) according to the invention, as well as measurements of surface tension and viscosity, are the subject of current work by the inventors.

[0376] The present invention thus provides new amino acid derivatives that can be used not only as surfactants, but also as thickening or gelling agents.

Claims

PATENT CLAIMS 1. Use of amino acid derivatives as surfactants in a surfactant-containing aqueous formulation, characterized in that i) the aqueous formulation as surfactant comprises at least one amino acid derivative of the following formula (I): in which R 1 selected from linear, branched or cyclic hydrocarbon residues with 4 to 26 carbon atoms, in which at least one carbon atom may be replaced by an oxygen or sulfur atom, the R 2 and the R 3 each independently selected from hydrogen and linear, branched or cyclic hydrocarbon residues with 1 to 26 carbon atoms, in which at least one carbon atom may be replaced by an oxygen or sulfur atom, R 5selected from divalent hydrocarbon residues with 1 to 6 carbon atoms, in which optionally at least one carbon atom is replaced by an oxygen or nitrogen atom and which optionally are substituted with -OH or -COOH, R 4 and R 6 selected from hydrogen and hydrocarbon residues with 1 to 8 carbon atoms, in which optionally at least one carbon atom is replaced by an oxygen or nitrogen atom and which optionally are substituted with -OH or -COOH, wherein R 4 and R 5 or R 4 and R 6 possibly connected to each other and together with the nitrogen atom or the carbon atom to which they are bonded, form a 5- or 6-membered heterocyclic ring, R 7is selected from -OH and an amino residue of an α-amino acid or a di- or oligopeptide thereof, together with the carbonyl group to which it is bonded, to form the free amino acid or a di-, tri- or higher oligopeptide, or stands for a sodium or potassium salt thereof, and n = 1, 2 or 3; and ii) that at least one surfactant of formula (I) simultaneously serves as a thickening or gelling agent, wherein the viscosity of the aqueous formulation is adjusted by controlling its pH value and / or its temperature.

2. Use according to claim 1, characterized in that the viscosity of the surfactant-containing aqueous formulation a) by reducing the pH, possibly to a value < 3; or b1) is reduced by increasing the pH, possibly to a value > 10, and / or b2) is reduced by increasing the temperature, possibly to a temperature > 45 °C.

3. Use according to claim 1 or 2, characterized in that R 1 stands for Ce-C22 alkyl; and / or the R 2 each are independently selected from hydrogen, Ci-C22 alkyl and Ci-C22 alkoxy; and / or the R 3 each are independently selected from hydrogen, methyl and methoxy; where, if necessary, a1) R 1 for Cs-C alkyl and / or a2) the R 2 each are independently selected from hydrogen, Ci-C4-alkyl and Ci-C4-alkoxy and / or a3) the R 3 each are hydrogen; or b1) R 1 Cs-Ci8-alkyl stands for a residue R 2 for -OR 1 stands, the other remainder R 2 Hydrogen or methoxy is and the R 3 each are hydrogen or b2) R 1 stands for Cs-Cis-Alkyl, the R 2each are hydrogen or methoxy and the R 3 Each is hydrogen.

4. Use according to one of claims 1 to 3, characterized in that a) R 5 selected from divalent hydrocarbon residues with 1 to 5 carbon atoms, in which at least one carbon atom may be replaced by an oxygen or nitrogen atom, and R 4 and R 6 each independently selected from methyl, hydroxymethyl, carboxymethyl, 1- or 2-hydroxyethyl and 1- or 2-carboxyethyl or R 4 stands for hydrogen; or b) R 4 and R 5 or R 4 and R 6 are interconnected alkylene groups which, together with the nitrogen atom or the carbon atom to which they are bonded, form a 5- or 6-membered heterocyclic ring, which may optionally be substituted with -OH or -COOH; or c) R 6comprising a 5- or 6-membered aromatic ring, which may optionally be a benzene or imidazole ring.

5. Use according to any one of claims 1 to 4, characterized in that R 4 , R 5 and R 6 are selected such that the grouping R 7 OC-CH2R 5 R 6 -NR 4 - in formula (I) for the amino residue, optionally further substituted with -OH or -COOH, of an amino acid selected from glycine, alanine, serine, aspartic acid, proline, pipecolic acid, phenylalanine and histidine, if R 7 for OH, or one of its diols or oligopeptides with the α-amino acid or its di- or oligopeptide, as in R 7 defined, stands.

6. Use according to any one of claims 1 to 5, characterized in that R 7 a remainder of the formula -(NR 4 -CHR 5 R 6 -CO) P -OH is, in which R 4 , R 5 and R 6as defined above, where p represents an integer from 0 to 10; where applicable p = 0 such that R 7 for OH, and the amino acid derivative of formula (I) is a derivative of an amino acid selected from glycine, alanine, serine, aspartic acid, proline, pipecolic acid, phenylalanine and histidine, optionally further substituted with -OH or -COOH; or p = 1 to 10, the R 4 and the R 5 in formula (I) are each identical and the amino acid derivative of formula (I) comprises a di- or oligopeptide of an amino acid selected from glycine, alanine, serine, aspartic acid, proline, pipecolic acid, phenylalanine and histidine, optionally further substituted with -OH or -COOH.

7. Amino acid derivative of the following formula (I): in which R 1selected from linear, branched or cyclic hydrocarbon residues with 4 to 26 carbon atoms, in which at least one carbon atom may be replaced by an oxygen or sulfur atom, the R 2 and the R 3 each independently selected from hydrogen and linear, branched or cyclic hydrocarbon residues with 1 to 26 carbon atoms, in which at least one carbon atom may be replaced by an oxygen or sulfur atom, R 5 selected from divalent hydrocarbon residues with 1 to 6 carbon atoms, in which optionally at least one carbon atom is replaced by an oxygen or nitrogen atom and which optionally are substituted with -OH or -COOH, R 4 and R 6selected from hydrogen and hydrocarbon residues with 1 to 8 carbon atoms, in which optionally at least one carbon atom is replaced by an oxygen or nitrogen atom and which optionally are substituted with -OH or -COOH, wherein R 4 and R 5 or R 4 and R 6 possibly connected to each other and together with the nitrogen atom or the carbon atom to which they are bonded, form a 5- or 6-membered heterocyclic ring, R 7 is selected from -OH and an amino residue of an α-amino acid or a di- or oligopeptide thereof, together with the carbonyl group to which it is bonded, to form the free amino acid or a di-, tri- or higher oligopeptide, or stands for a sodium or potassium salt thereof and n = 1, 2 or 3.

8. Amino acid derivative according to claim 7, characterized in that R 1stands for Ce-C22 alkyl; and / or the R 2 each are independently selected from hydrogen, Ci-C22 alkyl and Ci-C22 alkoxy; and / or the R 3 each are independently selected from hydrogen, methyl and methoxy; where, if necessary, a1) R 1 for Cs-C alkyl and / or a2) the R 2 each are independently selected from hydrogen, Ci-C4-alkyl and Ci-C4-alkoxy and / or a3) the R 3 each are hydrogen; or b1) R 1 Cs-Ci8-alkyl stands for a residue R 2 for -OR 1 stands, the other remainder R 2 Hydrogen or methoxy is and the R 3 each are hydrogen or b2) R 1 stands for Cs-Cis-Alkyl, the R 2 each are hydrogen or methoxy and the R 3 Each is hydrogen.

9. Amino acid derivative according to claim 7 or 8, characterized in that a) R 5selected from divalent hydrocarbon residues with 1 to 5 carbon atoms, in which at least one carbon atom may be replaced by an oxygen or nitrogen atom, and R 4 and R 6 each independently selected from methyl, hydroxymethyl, carboxymethyl, 1- or 2-hydroxyethyl and 1- or 2-carboxyethyl or R 4 stands for hydrogen; or b) R 4 and R 5 or R 4 and R 6 are interconnected alkylene groups which, together with the nitrogen atom or the carbon atom to which they are bonded, form a 5- or 6-membered heterocyclic ring, which may be substituted with -OH or -COOH; or c) R 6 comprising a 5- or 6-membered aromatic ring, which may optionally be a benzene or imidazole ring.

10. Amino acid derivative according to one of claims 7 to 9, characterized in that R 4 , R 5 and R6 are selected such that the grouping R 7 OC-CH2R 5 R 6 - NR 4 - in formula (I) for the amino residue, optionally further substituted with -OH or -COOH, of an amino acid selected from glycine, alanine, serine, aspartic acid, proline, pipecolic acid, phenylalanine and histidine, if R 7 for OH, or one of its di- or oligopeptides with the α-amino acid or its di- or oligopeptide, as in R 7 defined, stands.

11. Amino acid derivative according to one of claims 7 to 10, characterized in that R 7 a remainder of the formula -(NR 4 -CHR 5 R 6 -CO) P -OH is, in which R 4 , R 5 and R 6 as defined above, where p represents an integer from 0 to 10; where applicable p = 0 such that R 7for OH, and the amino acid derivative of formula (I) is a derivative of an amino acid selected from glycine, alanine, serine, aspartic acid, proline, pipecolic acid, phenylalanine and histidine, optionally further substituted with -OH or -COOH; or p = 1 to 10 is the R 4 and the R 5 in formula (I) are each identical and the amino acid derivative of formula (I) comprises a di- or oligopeptide of an amino acid selected from glycine, alanine, serine, aspartic acid, proline, pipecolic acid, phenylalanine and histidine, optionally further substituted with -OH or -COOH.

12. Amino acid derivative according to one of claims 7 to 11, characterized in that it is selected from the following compounds: N-(4-Dodecyloxy-3-methoxybenzyl)proline (1) N-(4-Dodecyloxy-3-methoxybenzyl)-4-hydroxyproline (2) N-(3-(4-Dodecyloxy-3-methoxyphenyl)propyl)prolin (4) N-(4-Dodecyloxybenzyl)prolin (7) N-(4-Dodecyloxybenzyl)-4-hydroxyprolin (8) N-(4-Dodecyloxybenzyl)pipecolinsäure (9) N-(4-Dodecyloxy-3-methoxybenzyl)piperidin-4-carbonsäure (11) 2,2'-((4-Dodecyloxy-3-methoxybenzyl)azandiyl)diessigsäure (14) 2,2'-((4-Dodecyloxy-3-methoxybenzyl)azandiyl)diessigsäure-Dinatriumsalz (15) N-(4-Octyloxy-3-methoxybenzyl)prolin (16) N-(4-Dodecyloxy-3-methoxyphenethyl)-4-hydroxyprolin (18) N-(4-Dodecyloxy-3-methoxyphenethyl)piperidin-4-carbonsäure (19) N-(3-(4-Decyloxy-3-methoxyphenyl)propyl)prolin (21) N-(3-(4-Dodecyloxyphenyl)propyl)prolin (22) N-(4-Dodecyloxy-3-methoxybenzyl)glycin-Natriumsalz (23) N-(4-Dodecyloxy-3-methoxybenzyl)alanin-Natriumsalz (24) coo Na + N-(4-Dodecyloxy-3-methoxybenzyl)phenylalanin-Natriumsalz (25) N-(4-Dodecyloxy-3-methoxybenzyl)tyrosin-Natriumsalz (26) N-(4-Dodecyloxy-3-methoxybenzyl)serin-Natriumsalz (27) N-(4-Dodecyloxy-3-methoxybenzyl)histidin-Natriumsalz (28) N-(4-Dodecyloxy-3-methoxybenzyl)-ß-alanin-Natriumsalz (29) N-(4-Octadecyloxy-3-methoxybenzyl)tyrosin-Natriumsalz (30) N-(4-Dodecyloxy-3-methoxybenzyl)glycylglycin-Natriumsalz (31 ) 13. A process for the production of amino acid derivatives according to any one of claims 7 to 12, comprising the following steps: 1) the reaction of the free phenolic OH group(s) of a 4-hydroxyalkylphenol derivative of formula (II) below or, in the case of derivatives with n = 1, of a 4-hydroxybenzaldehyde derivative of formula (III) below: in which the R 3 each independently selected from hydrogen and linear, branched or cyclic hydrocarbon residues with 1 to 26 carbon atoms, in which optionally at least one carbon atom is replaced by an oxygen or sulfur atom, and the R 8 each independently from -OH and the options for R 3 are selected with a combination of the formula R 1 -Y, wherein R 1selected from linear, branched or cyclic hydrocarbon residues with 4 to 26 carbon atoms, in which optionally at least one carbon atom is replaced by an oxygen or sulfur atom, and Y represents a leaving group selected from halides and sulfonates, by means of an etherification reaction according to Williamson in the presence of a base in an organic solvent, wherein the compound of formula R 1 -Y is used in an amount of less than 1 equivalent per equivalent of phenolic OH groups of the derivative of formula (II) or (III), giving a corresponding ether of formula (IV) or (V): in which the R 2 each independently from -OR 1 and the options for R 3 are selected and where in formula (IV) n = 1, 2 or 3; and 2a) the direct reaction of the ether of formula (IV) with an amino acid or a di- or oligopeptide thereof or 2b) the reduction of the ether of formula (V) to the ether of formula (IV) with n = 1 and its subsequent reaction with an amino acid or a di- or oligopeptide thereof or 2c) the direct reaction of the ether of formula (V) with an amino acid or a di- or oligopeptide thereof under a hydrogen atmosphere, each in the presence of a Shvo catalyst, to obtain the corresponding amino acid derivative of formula (I): in which R 5 selected from divalent hydrocarbon residues with 1 to 6 carbon atoms, in which optionally at least one carbon atom is replaced by an oxygen or nitrogen atom and which optionally are substituted with -OH or -COOH, R 4 and R 6selected from hydrogen and hydrocarbon residues with 1 to 8 carbon atoms, in which optionally at least one carbon atom is replaced by an oxygen or nitrogen atom and which optionally are substituted with -OH or -COOH, wherein R 4 and R 5 or R 4 and R 6 may be linked together and, together with the nitrogen atom or the carbon atom to which they are bonded, form a 5- or 6-membered heterocyclic ring, R 7 from -OH and an amino residue of an α-amino acid or a di- or oligopeptide thereof is selected to form, together with the carbonyl group to which it is bound, the free amino acid or a di-, tri- or higher oligopeptide, and n = 1, 2 or 3.

14. Method according to claim 13, characterized in that potassium carbonate K2CO3 is used as the base in step 1). is used as the organic solvent acetonitrile CH3CN and / or as a compound of the formula R 1 -Y a bromide or chloride is used; where, if necessary, in step 1) Pre-dried powdered K2CO3 is used as a base, is used as an organic solvent, anhydrous CH3CN, and / or as a compound of formula R 1 -Y a bromide is used; where, if necessary, in step 1) the organic solvent is refluxed and / or the connection of the formula R 1 -Y is used in an amount of 0.96 to 0.99 equivalents per equivalent of phenolic OH groups of the derivative of formula (II) or (III).

15. Method according to claim 13 or 14, characterized in that in step 2) the ether of formula (V) obtained in step 1) is first reduced according to step 2b) to the ether of formula (IV) with n = 1, which is then reacted with the amino acid or a di- or oligopeptide thereof, wherein the reduction is optionally carried out in the presence of a palladium catalyst under a hydrogen atmosphere; wherein, optionally in step 2), the ether of formula (IV) or (V) is reacted in a protic solvent under reflux, optionally under a hydrogen atmosphere, with the amino acid or a di- or oligopeptide thereof, wherein the protic solvent is optionally trifluoroethanol.

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