C-glycoside amine derivatives and their preparation methods

Abstract

The present invention discloses a C-glycoside amine derivative as shown in the following formula: R-CH2-C(CH3)-NH-R2, wherein R is a glycosylated compound (e.g., as described in U.S. Patent 8,314,219) and R2 is the acyl moiety of any ketone derived from the formula R3-C(O)-R3, wherein R3 is a C1 to C22 straight-chain or branched hydrocarbon, which may be saturated or unsaturated. Furthermore, the method for preparing C-glycoside amine derivatives includes (1) reacting a glycoside (e.g., glucose) C-glycoside ketone with a catalyst (e.g., Rh), about 10 to about 25 times the excess of NH3 and an organic solvent (e.g., methanol) to form a glycoside C-glycoside amine, and (2) reacting the glycoside C-glycoside amine with a catalyst (e.g., Rh), an organic solvent (e.g., methanol) and an acyl moiety derived from any ketone of the formula R3-C(O)-R3 to form the C-glycoside amine derivative, wherein R3 is a C1 to C22 straight-chain or branched hydrocarbon, which may be saturated or unsaturated.

Description

[0001] Refer to relevant applications

[0002] This application claims priority to U.S. Provisional Application No. 62 / 958,987, filed January 9, 2020, the entire contents of which are incorporated herein by reference. Background Technology

[0003] This invention discloses C-glycoside amine derivatives represented by the following formula:

[0004] R-CH2-C(CH3)-NH-R2

[0005] Wherein R is a glycosylated compound (e.g., as described in U.S. Patent 8,314,219), and R2 is an acyl moiety derived from any ketone of the formula R3-C(O)-R3, wherein R3 is a C1 to C22 straight-chain or branched hydrocarbon, which may be saturated or unsaturated. Compositions comprising at least one C-glycosidic acid derivative are also disclosed. Furthermore, a method for preparing a C-glycosidic acid derivative comprises (1) reacting a glycosylated compound (e.g., glucose) C-glycosidic acid ketone with a catalyst (e.g., Rh), about 10 to about 25 times the excess of NH3, and an organic solvent (e.g., methanol) to form a glycosylated C-glycosidic acid, and (2) reacting said glycosylated C-glycosidic acid with a catalyst (e.g., Rh), an organic solvent (e.g., methanol), and an acyl moiety derived from any ketone of the formula R3-C(O)-R3 to form said C-glycosidic acid derivative, wherein R3 is a C1 to C22 straight-chain or branched hydrocarbon, which may be saturated or unsaturated.

[0006] There is a growing awareness of the need for bio-based and sustainable chemicals. This is particularly evident in the consumer goods sector, where the demand for natural ingredients is increasing. In this trend, glycosyl surfactants consist of a hydrophilic sugar head group (typically glucose, fructose, maltose, or sucrose) and a hydrophobic alkyl tail. The alkyl tail is typically derived from triacylglycerols, with carbon chain lengths of 8 to 22, and can be saturated or unsaturated. Due to this general composition of sugars and fatty acids, these compounds are considered biodegradable, and these nonionic amphiphiles are commonly used as emulsifiers in food, cosmetics, pharmaceuticals, and detergents. Neta et al. wrote a review on the synthesis of glycoesters (Neta, NS, et al., Crit. Rev. Food Sci. Nutr., 55:595-610 (2015)).

[0007] Carbohydrates of interest to synthetic surfactants are widely available. Glucose is the most abundant monosaccharide, produced by the enzymatic hydrolysis of starch. Maltose is a glucose dimer with α (1→4) bonds, produced by hydrolyzing starch with α-amylase to prepare maltose syrup, with a maltose content as high as 80 wt% (Zhou, J., et al., Appl. Environ. Microbiol., 84:1-12 (2018)). Maltose is used in the pharmaceutical industry for tableting, and in the food industry it can enhance subtle flavors that are overwhelmed by the sweetness of sucrose (Jeong, SH, et al., J. Mater. Chem., 18:3527-3535 (2008)). Lactose may be a more interesting carbohydrate because it is a dairy waste product. Cheese production produces large quantities of liquid whey. Whey contains 5% lactose and is a high-BOD waste that requires remediation (Das, B., et al., Process Saf. Environ. Prot., 101:27-33 (2016); Carvalho, F., et al., Sci. Total Environ., 445-446, 385-396 (2013)). The cost-effective utilization of lactose streams has been a focus of the dairy industry for decades (Hobman, PG, J. Dairy Sci., 67:2630-2653 (1984); de Souza, RR, et al., Chem. Eng. Process. Process Intensif., 49:1137-1143 (2010)). Lactose is rarely used as a surfactant (Drummond, CJ, and D. Wells, Colloids Surf APhysicochem Eng Asp, 141:131-142 (1998); Wilk, KA, et al., J. Surfactants Deterg., 4:155-161 (2001); Perinelli, DR, et al., Eur J Pharm Biopharm, 124:55-62 (2018)).

[0008] In this paper, we describe the synthesis and properties of a series of novel surfactants prepared from β-C-glycosidic amines and medium-chain ketones, some of which can be chemically prepared from medium- and long-chain fatty acids. These compounds have the potential to serve as sustainable and environmentally friendly emulsifiers. For example, the sugar head group can be derived from crop residues and dairy byproducts. For instance, the hydrophobic tail can be synthesized via ketation of triglycerides from *Cuphea sp.* (Jackson et al. 2012), a promising new type of marginal land row crop in temperate regions. Invention Overview

[0010] This invention discloses C-glycoside amine derivatives represented by the following formula:

[0011] R-CH2-C(CH3)-NH-R2

[0012] Wherein R is a glycosylated compound (e.g., as described in U.S. Patent 8,314,219) and R2 is an acyl moiety derived from any ketone of the formula R3-C(O)-R3, wherein R3 is a C1 to C22 straight-chain or branched hydrocarbon, which may be saturated or unsaturated. Compositions comprising at least one C-glycosidic acid derivative are also disclosed. Furthermore, a method for preparing a C-glycosidic acid derivative comprises (1) reacting a glycosylated compound (e.g., glucose) C-glycosidic acid ketone with a catalyst (e.g., Rh), about 10 to about 25 times the excess of NH3, and an organic solvent (e.g., methanol) to form a glycosylated C-glycosidic acid, and (2) reacting said glycosylated C-glycosidic acid with a catalyst (e.g., Rh), an organic solvent (e.g., methanol), and an acyl moiety derived from any ketone of the formula R3-C(O)-R3 to form said C-glycosidic acid derivative, wherein R3 is a C1 to C22 straight-chain or branched hydrocarbon, which may be saturated or unsaturated.

[0013] This overview is provided to introduce some concepts in a simplified form, which will be further described in detail below. This overview is not intended to identify key or essential features of the claimed subject matter, nor is it intended to help determine the scope of the claimed subject matter. Attached Figure Description

[0014] Example image Figure 1 This is an example of a general reaction scheme for preparing C-glycosidones from glucose and pentane-2,4-dione as described below; the same chemical reaction applies to other glycosides such as galactose, xylose, maltose, and lactose.

[0015] Example image Figure 2This is an example of a general reaction scheme showing the two-step conversion of glucose-C-glycosidone to glucose-C-glycoside 2-aminoundecane, as described below. Both steps are carried out at 75°C and 34 bar H₂ pressure. The first reductive amination is carried out at 1.4 bar NH₃, while the second reductive amination is carried out with 10 mol% excess 2-undecane.

[0016] Detailed description of the invention

[0017] This invention discloses C-glycoside amine derivatives represented by the following formula:

[0018] R-CH2-C(CH3)-NH-R2

[0019] Wherein R is a glycosylated compound (e.g., as described in U.S. Patent 8,314,219) and R2 is an acyl moiety derived from any ketone of the formula R3-C(O)-R3, wherein R3 is a C1 to C22 straight-chain or branched hydrocarbon, which may be saturated or unsaturated. Compositions comprising at least one C-glycosidic acid derivative are also disclosed. Furthermore, a method for preparing a C-glycosidic acid derivative comprises (1) reacting a glycosylated compound (e.g., glucose) C-glycosidic acid ketone with a catalyst (e.g., Rh), about 10 to about 25 times the excess of NH3, and an organic solvent (e.g., methanol) to form a glycosylated C-glycosidic acid, and (2) reacting said glycosylated C-glycosidic acid with a catalyst (e.g., Rh), an organic solvent (e.g., methanol), and an acyl moiety derived from any ketone of the formula R3-C(O)-R3 to form said C-glycosidic acid derivative, wherein R3 is a C1 to C22 straight-chain or branched hydrocarbon, which may be saturated or unsaturated.

[0020] In preparing the amphiphiles, we used β-C-glycosidic ketones as precursors (Lubineau, A., et al., Carbohydr. Res., 266:211-219 (1995); Price, NPJ, et al., J. Mass Spectrom., 43:53-62 (2008)). These derivatives were prepared in high yields by the condensation reaction of pentane-2,4-diones with, for example, aldoses in weakly alkaline aqueous solutions. Figure 1Under thermodynamic control, high stereoselectivity for β-terminal isomers was achieved (Riemann, I., et al., Aust. J. Chem., 55: 147-154 (2002)). The attractiveness of these compounds as substrates is twofold. First, the sugar is locked in its β-pyranose form, eliminating the complex sugar infusions that occur through equilibrium mixtures of their usual linear, pyranose, and furanose forms. Second, the β-C-glycosidones are soluble in organic solvents (e.g., methanol), eliminating the challenges inherent in the use of water, such as its high boiling point. Sugars suitable for this chemistry include, for example, xylose, lythose, ribose, arabinose, glucose, mannose, N-acetylglucosamine, cellobiose, maltose, lactose, galactose, allose, atroose, and polymers of these sugars.

[0021] An example of an aliphatic tail that can be attached to a glycoside head group can be derived, for example, from the seed oil of *Cupheasp.*. As previously mentioned, *Cupheasp.* seed oil may be particularly suitable for cross-ketalization with acetic acid (Jackson, MA, et al., Appl. Catal., A Gen., 431-432, 157-163 (2012)). This condensation reaction converts two carboxylic acids to ketones while eliminating CO2 and water. For example, two acetic acid molecules react to form acetone. The fatty acid composition of *Cupheasp.* seed triglycerides is typically about 72% decanoic acid. In the ketalization reaction with acetic acid, decanoic acid is converted to 2-undecanoic acid in 90% yield. The aliphatic tail can also be any other C3-C22 ketone, such as from 2-pentanone to 2-nonadecanone and 10-nonadecanone.

[0022] A novel, general method for preparing C-glycosidic amines: In a stirred reactor, C-glycosidones (e.g., 5 g), a hydrogenation catalyst (e.g., 500 mg 2 wt% Rh / C (rhodium on any support other than platinum and palladium)) and an organic solvent, such as an alcohol like MeOH (e.g., 50 ml) or ethanol, are added. The reactor is purged, for example, with hydrogen (or an inert gas such as nitrogen or argon) to remove air before the addition of NH3 (e.g., about 1.5 to about 3.1 bar (1.5-3.1 bar) anhydrous). The reactor is then heated to about 65°C to about 100°C (e.g., 65°C to 100°C), while being purged with H2 to about 17 to about 70 bar (e.g., 17 to 70 bar). The reaction progress is monitored by MALDI-TOF (matrix-assisted laser desorption / ionization-time-of-flight) mass spectrometry. After completion (typically about 1 to about 6 hours (e.g., 1-6 hours)), the reactor is vented and cooled. The catalyst is collected by filtration, and the product is collected from the filtrate by removing the solvent under reduced pressure.

[0023] Reductive amination of ketones or aldehydes with NH3 typically yields secondary amines because primary amines are more reactive than NH3 (Nakamura, Y., et al., ChemCatChem, 7:921-924 (2015)). We surprisingly solved this potential problem by introducing a molar excess of NH3 in the reactor (compared to β-C-glycosidones) of about 10 to about 25 times (e.g., 10-25 times). Indeed, in organic solvents (e.g., methanol) and with the aid of a catalyst (e.g., 2 wt% Rh / HMS), the reductive amination of C-glycosidones of saccharides (e.g., glucose, maltose, lactose) with NH3 proceeds unexpectedly readily within about 1 to about 6 hours (e.g., 1-6 hours), with little indication that the amine reaction forms secondary amines or dimer products. Figure 2 ).

[0024] A novel, general method for preparing C-glycoside surfactants: the addition of an alkyl chain that imparts amphiphilic properties to the compound is also accomplished via reductive amination (RA). The second RA occurs between a C-glycoside amine and, for example, 2-undecaneone (or other ketones as described above). These reactions are carried out in solvents soluble in C-glycosides (e.g., organic solvents such as methanol and ethanol, or water) and catalyzed by a hydrogenation catalyst (e.g., 5 wt% Rh / C (rhodium is effective on any support other than platinum and palladium)). As described in the first step above, the reactor is purged with hydrogen or an inert gas (nitrogen or argon) and then heated to approximately 65°C to approximately 100°C (e.g., 65°C to 100°C). The reactor is then charged with approximately 17 to approximately 70 bar of hydrogen (e.g., 17-70 bar) and the reaction is completed within approximately 3 to approximately 18 hours (e.g., 3-18 hours). This method unexpectedly avoids the limitation of nonspecific regioselectivity, which affects the chemical esterification of sugars with fatty acids (van Kempen, SEHJ, et al., Food Chem., 138:1884-1891 (2013)). As described below, we prepared 2-aminoundecane derivatives of glucose, lactose, maltose, and maltotriose. Other possible ketal alkyl groups include, for example, 2-tetadecanone, 2-pentadecanone, 2-heptadecanone, 10-nonadecanone, and 2-nonadecanone. Reductive amination was carried out using, for example, rhodium as the active metal. Effective supports include, for example, Al₂O₃, HMS-SiO₂, C, and zeolite ZSM-5, β- and mordenite.

[0025] The above method does not use homogeneous catalysts (e.g., Raney nickel), acyl chloride compounds, or irritating solvents known to be required for the preparation of sugar esters (Wilk, KA, et al., J. Surfactants Deterg, 4(2):155-161 (2001); Drummond, CJ, and D. Wells, Coll. Surf. A: Physicochem. Eng. Asp., 141:131-142. (1998)). It also does not require long reaction times (e.g., about 48 to about 72 hours (48-72 hours)), for example, in enzyme-mediated reactions (Zhao, L, et al., Food Chem, 187:370-377. (2015)).

[0026] Other compounds (e.g., surfactants known in the art) may be added to the composition, provided that they do not substantially interfere with the intended activity and efficacy of the composition; whether a compound interferes with activity and / or efficacy can be determined by, for example, the methods used below.

[0027] The terms "optional" or "optionally" mean that an event or condition described subsequently may or may not occur, and the description includes instances where the event or condition occurs and instances where it does not occur. For example, the phrase "optionally contains a known surfactant" means that the composition may or may not contain a known surfactant, and the description includes compositions containing and not containing a known surfactant. Furthermore, by way of example, the phrase "optionally adds a known surfactant" means that the method may or may not involve adding a known surfactant, and the description includes methods involving and not involving adding a known surfactant.

[0028] The term "effective amount" for a compound or property as used herein refers to the amount sufficient to achieve the function of the compound or property represented by the effective amount. As will be noted below, the exact amount required will vary depending on the process, which depends on recognized variables such as the compound used and the observed processing conditions. Therefore, it is not possible to specify an exact "effective amount." However, a suitable effective amount can be determined by those skilled in the art using only routine experiments.

[0029] The compound or composition described herein to be used will be at least an effective amount of the compound or a diluted solution of the compound; for fumigation, the compound used may have to be in pure form (not to be mixed or adulterated with any other substance or material). Typically, the concentration of the compound will be, but not limited to, from about 0.025% to about 10% (e.g., 0.025% to 10%, for example, in an aqueous solution), preferably from about 0.5% to about 4% (e.g., 0.5% to 4%), more preferably from about 1% to about 2% (e.g., 1% to 2%). The composition may or may not contain insect control agents, such as biological control agents or insecticides known in the art for killing insects. Other compounds (e.g., insect attractants or other insecticides known in the art) may be added to the composition, provided that they do not substantially interfere with the intended activity and efficacy of the composition; whether a compound interferes with activity and / or efficacy can be determined by, for example, the methods used below.

[0030] Compositions containing the compounds disclosed herein may optionally include a carrier (e.g., an agronomically, physiologically, or pharmaceutically acceptable carrier). The carrier component may be a liquid or solid material. As used herein, the term "carrier" includes carrier materials as described below. As is known in the art, the medium or carrier used refers to a matrix, such as mineral oil, paraffin wax, silicone oil, water, membranes, pouches, discs, ropes, vials, tubes, diaphragms, resins, hollow fibers, microcapsules, cigarette filters, gels, fibers, natural and / or synthetic polymers, elastomers, etc. All of these matrices have been used to control the release of effective amounts of compositions containing the compounds disclosed herein and are well known in the art. Suitable carriers are well known in the art and are selected based on the end application of interest. Agronomically acceptable substances include aqueous solutions, glycols, alcohols, ketones, esters, hydrocarbons, halogenated hydrocarbons, polyvinyl chloride; in addition, solid carriers such as clay, laminates, cellulose and rubber matrices, and synthetic polymer matrices, etc.

[0031] While the invention may be embodied in many different forms, specific preferred embodiments of the invention are described in detail herein. This disclosure is exemplary of the principles of the invention and is not intended to limit the invention to the specific embodiments shown. All patents, patent applications, scientific papers, and any other references mentioned herein are incorporated herein by reference in their entirety. Furthermore, the invention covers any possible combination of some or all of the various embodiments and features described and / or incorporated herein. Moreover, the invention includes any possible combinations that also expressly exclude any one or some of the various embodiments and features described and / or incorporated herein.

[0032] The quantities, percentages, and ranges disclosed herein are not intended to be limiting, and the increments between said quantities, percentages, and ranges are specifically considered part of the invention. All ranges and parameters disclosed herein should be understood to encompass any and all subranges contained herein, as well as every number between the endpoints. For example, the specified range of “1 to 10” should be considered to include any and all subranges between the minimum value of 1 and the maximum value of 10, including all integer and decimal values; that is, all subranges begin with a minimum value of 1 or greater (e.g., 1 to 6.1), end with a maximum value of 10 or less (e.g., 2.3 to 9.4, 3 to 8, 4 to 7), and finally to every number 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 contained within that range.

[0033] Unless otherwise stated, all figures used in the specification and claims to represent the amount, properties such as molecular weight, reaction conditions (e.g., reaction time, temperature), percentages, etc., of components should be understood to be modified by the term "about" in all cases. Therefore, unless otherwise stated, the numerical properties set forth in the following specification and claims are approximate values ​​that may vary depending on the desired properties sought to be obtained in embodiments of the invention. As used herein, the term "about" refers to a quantity, level, value, or amount that varies by up to 10% relative to a reference quantity, level, value, or amount. For example, about 1.0 g represents 0.9 g to 1.1 g and all values ​​within that range, whether explicitly stated or not.

[0034] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Although any methods and materials similar to or equivalent to those described herein may be used in the practice or testing of this invention, preferred methods and materials are now described.

[0035] The following examples are for further illustration of the present invention and are not intended to limit the scope of the invention as defined in the claims. Example

[0036] Preparation of C-glycosidic acid: 5g of C-glycosidone was added to a 300ml Parr instrument stirred reactor. Figure 1 The reaction mixture consisted of 500 mg 2wt% Rh / C and 50 mL MeOH. The reactor was purged with hydrogen to remove air before adding 30 psi of anhydrous NH3. The reactor was then heated to 75 °C and pressurized to 500 psi with H2. The reaction progress was monitored by MALDI-TOF (matrix-assisted laser desorption / ionization-time-of-flight) mass spectrometry. After completion (typically approximately 1 to 4 hours), the reactor was vented and cooled. The catalyst was collected by filtration, and the product was collected from the filtrate by removing the solvent under reduced pressure.

[0037] As mentioned above, the reductive amination of ketones or aldehydes with NH3 usually yields secondary amines because primary amines are more reactive than NH3 (Nakamura, Y., et al., ChemCatChem, 7:921-924 (2015)). This potential problem was unexpectedly resolved by adding 10-25 molar excess NH3 to the reactor. In fact, the reductive amination of C-glycosidates of glucose, maltose, and lactose with NH3 in methanol over a 2 wt% Rh / HMS catalyst proceeded surprisingly readily, with little indication that the amine reaction formed secondary amines or dimer products. Figure 2 ).

[0038] Preparation of C-glycoside surfactants: As mentioned above, the addition of the alkyl chain that imparts amphiphilic properties to the compounds is also accomplished via reductive amination (RA). The second RA is intermediate between C-glycoside amines and 2-undecane. These reactions are carried out in methanol and catalyzed by 5 wt% Rh / C. As mentioned above, this method unexpectedly avoids the limitation of nonspecific regioselectivity that affects the chemical esterification of sugars with fatty acids (van Kempen, SEHJ, et al., Food Chem., 138:1884-1891 (2013)). We prepared 2-aminoundecane derivatives of four glycosides (i.e., glucose, lactose, maltose, and maltotriose).

[0039] NMR and MALDI-TOF MS data for ketones, amines and 2-aminoundecane:

[0040] Glucose C-glycosidone: 1H NMR (500MHz, D2O) δ 3.80 (m, 1H), 3.60 (m, 1H), 3.70 (m, 1H), 3.40 (t, J = 8.9 Hz, 1H), 3.30 (m, 2H), 3.1 (t, 1H), 2.95 (dd, J = 3.2, J = 16 Hz, 1H), 2.66 (dd, J = 9.0, J = 16 Hz, 1H), 2.20 (s, 3H). 13C NMR (125MHz, D2O) δ 213, 79.5, 77.3, 75.3, 73.2, 69.9, 60.7, 45.7, 30.0. MALDI-TOF MS: m / z 243, [M+Na]+.

[0041] Glucose C-glycosylamine: 1H NMR (500MHz, D2O acidified with D2SO4). δ 3.80(m, 1H), 3.60(m, 1H), 3.70(m, 1H), 3.32(m, 1H), 3.30(m, 1H), 3.18 and 3.15(t, J = 6.8 Hz, 2H), 1.81 and 1.75(m, J = 2.2 Hz, 1H), 1.52(m, J = 2.2 Hz, 1H), 1.20(dd, J = 6 Hz, 0.6H), 1.1(dd, J = 6 Hz, 2.4H). 13C NMR (125 MHz, D2O acidified with D2SO4) δ 79.5, 77.8, 77.1, 73.7, 70.0, 61.1 2x, 44.5, 42.8, 39.7, 39.3, 22.3, 20.9, 20.1. MALDI-TOF MS: m / z 222,[M+H]+,244,[M+Na]+.

[0042] Glucose C-glycoside 2-aminoundecane: ¹H NMR (500MHz, DMSO-d6) δ 3.63 (m, 1H), 3.39 (m, 1H), 3.09 (m, 1H), 3.02 (m, 1H), 2.84 (m, 1H), 1.43 (m, 2H), 1.24 (bs, 16H), 0.93 (m, 6H), 0.85 (t, J = 7.3Hz, 3H). ¹³C NMR (125MHz, DMSO-d6) δ 80.8, 79.0, 75.0, 71.0, 62.0 2x, 32.0, 29.6, 25.7, 24.0, 22.8, 21.9, 21.4, 14.5. MALDI-TOF MS: m / z 376, [M+H]+.

[0043] Maltose C-glycosidone: 1H NMR (500MHz, D2O). δ 5.33, 5.28 (d, J = 3.9Hz, 1H), 3.83, 3.79, 3.73, 3.72, 3.71, 3.70, 3.65, 3.55, 3.52, 3.48, 3.36 (overlapping m, 14H), 3.36 (t, J = 9.5Hz, 1.4H), 3.20 (t, J = 9.5Hz, 0.6H), 2.96, 2.94, 2.92, 2.87 (overlapping m, 1.4H), 2.66 (dd, J = 9.3Hz, 0.6H), 2.22 (s, 1.4H), 2.21 (s, 1.8H). 13C NMR (125MHz) D2O)δ213.2,212.9,99.6,99.5,78.1,77.7,77.0,76.8,75.1,73.0,72.9,72.9,72. 7,72.6,71.7,71.6,71.1,70.2,69.3,60.8,60.5,45.6,40.1,29.9,29.8.MALDI-TOF MS:m / z 405,[M+Na]+.

[0044] Maltose C-glycosides: ¹H NMR (500 MHz, D₂O). δ 5.33 (d, J = 3.9 Hz, ¹H), 3.78, 3.69, 3.67, 3.64, 3.54, 3.52, 3.46, 3.40, 3.39, 3.35 (overlap m, 22H), 1.95 (m, ¹H), 1.60 (m, ¹H), 1.18 (2d, J = 6.5 Hz, 2H). ¹³C NMR (125 MHz) D2O)δ99.6,77.9,77.7,77.6,77.1,77.0,73.5,72.9,72.7,72.7,71.7,71 .7,69.3,60.9,60.9,60.7,60.5,60.5,48.9,45.8,37.3,19.4.MALDI-TOF MS:m / z 384,[M+H]+,406,[M+Na]+.

[0045] Maltose C-glycoside 2-aminoundecane: ¹H NMR (500 MHz, D₂O acidified). 5.34, 5.29 (2 unresolved groups, ¹H), 3.85, 3.76, 3.66, 3.65, 3.64, 3.53, 3.52 (m, ¹⁴H), 3.36, 3.34 (m, 2.¹H), 3.17 (m, 0.6H), 1.60 (bs, ¹H), 1.42 (bs, ¹H), 1.27, 1.23, 1.18, 1.15 (bm, ¹⁹H), 0.74 (t, J = 6.7 Hz, ³H). ¹³C NMR (125 MHz) D2O)δ99.6,99.1,77.9,77.8,77.5,73.0,72.8,72.7,71.6,71.5,69.2,60 .9,60.5,51.9,49.6,32.5,31.2,22.1,16.3,15.8,15.3,13.4.MALDI-TOF MS: m / z 538,[M+H]+,560,[M+Na]+.

[0046] Lactose C-glycosidone: 1H NMR (500MHz, D2O). δ 4.50 (m, 0.4H), 4.38, 4.37 (d, J = 7.8Hz, 1H combined. These integrals are 2:1), 3.87 (dd, J = 3.3), 3.83, 3.74, 3.73, 3.71, 3.70, 3.66, 3.60, 3.57, 3.49, 3.48 (unresolved group, 13H), 3.22 (m, 0.6H), 2.96 (dd, J = 2.8Hz, J = 16.8Hz, 0.6H), 2.90 (m, 0.4H), 2.22, 2.21 (2 singlets, 3H). 13C NMR(125MHz D2O)δ102.9,78.7,78.5,78.3,75.8,75.4,75.1,72.8,72.5,72.3,71.7,71.6,71.0,70.1,68.6,61.0,60.1,45.6,39.7,29.8.MALDI-TOF MS: m / z 405,[M+Na]+.

[0047] Lactose C-glycosides: 1H NMR (500MHz, D2O). δ 4.36 (dJ = 7.8Hz, 1H), 3.87, 3.85, 3.70, 3.64, 3.58, 3.55, 3.53, 3.47, 3.45, 3.44 (overlap m, 15H), 3.19 (ddd, J = 3.1, J = 9, J = 20Hz, 1H), 1.97 (m, 1H), 1.66 (m, 1H), 1.21 (d, J = 6.7Hz, 3H). 13C NMR (125MHz) D2O)δ102.9,78.6,78.5,78.3,78.1,77.4,75.8,75.7,73.2,72.9,72.5,71.0 ,68.6,61.0,60.3,60.2,48.9,46.2,44.4,36.6,36.5,19.4,18.9.MALDI-TOF MS:m / z 384,[M+H]+,406,[M+Na]+.

[0048] Lactose C-glycoside 2-aminoundecane: ¹H NMR (500 MHz, D₂O, acidified). δ 4.31 (dt, J = 7.8 Hz, 1H), 3.84, 3.81, 3.65, 3.61, 3.60, 3.54, 3.50, 3.46, 3.42, 3.29, 3.17 (m, 17H), 2.1–1.7 (m, 2H), 1.59 (m, 1H), 1.42, 1.27 (t, J = 5.7 Hz, 3H), 1.16 (m, 15H), 0.74 (t, J = 7.1 Hz, 3H). ¹³C NMR (125 MHz) D2O)δ102.9,102.8,78.6,78.5,78.4,78.2,78.0,75.6,75.3,73.1,72.9,72.5,70.9,68.5,61.0,6 0.3,51.9,49.5,32.6,31.2,28.6,28.5,28.4,28.3,22.0,16.2,15.8,15.6,15.3,13.4.MALDI-TOF MS: m / z 538,[M+H]+,560,[M+Na]+.

[0049] Surfactants prepared from glucose, maltose, lactose, and 2-undecanene have critical micelle concentrations (CMC) ranging from 0.1 to 5.5 mM. CMC is an important property of surfactants. When amphiphiles are placed in water at concentrations close to the CMC, they aggregate, causing the polar head groups to form an outer surface that orients the alkyl tail within the core. This core exhibits properties similar to organic solvents. At concentrations above the CMC, the properties of the bulk solution change; for example, surface tension decreases, the solution wets surfaces better, and water-insoluble substances dissolve within the micelle core. Therefore, CMC is used to guide the application of surfactants in detergents, cosmetics, wetting agents, or food.

[0050] Antibiotic activity is an important property when surfactants are used in detergent formulations. The antimicrobial activities of surfactants prepared from saccharides glucose, maltose, and lactose, as well as 2-undecane, against several microorganisms of interest in the food, human health, and agricultural sectors were measured. The concentrations at which these compounds inhibited organism growth, i.e., the microbial inhibitory concentrations (MICs), were surprisingly low, down to 0.31 mM. These can be compared with known values ​​for saccharide fatty acid esters, such as those of Zhao et al. (Zhao, L., et al., Food Chem., 187:370-377 (2015)), who reported an MIC of 2.5 mM for sucrose decanoate against Bacillus subtilis and 10 mM against Escherichia coli. Staroń et al. reported a MIC of 5.9 mM for dodecanoyl lactose against Bacillus cereus (Staroń, J., et al., Crit. Rev. Biotechnol., 38:245-258 (2018)). The MIC of galactosyl laurate against Streptococcus mutans was 0.14 mM (Watanabe, T. et al., Curr. Microbiol., 41:210-213 (2000)). The CMC values ​​of β-C-glycoside 2-aminoundecane ranged from 0.1 to 5.5 mM. Surprisingly, β-C-glycoside 2-aminoundecane exhibits antimicrobial activity against Bacillus subtilis, Pseudomonas aeruginosa, Erwinia amylovora, Escherichia coli, and Mycobacterium smegmatis. The glucose derivative showed the greatest activity against all tested Gram-positive bacteria, with a minimum inhibitory concentration (MIC) of 0.31 mM and a minimum bactericidal concentration (MIC) of 0.62 mM. The MIC against Gram-negative Erwinia and Escherichia was surprisingly low at 0.62 mM.

[0051] Summary: β-C-glycosidic ketone derivatives of saccharides glucose, lactose, and maltose were converted to amines via reductive amination in ammonia-methanol using 2 wt% Rh / HMS (Rh / C or Rh / Al₂O₃ could be used) at approximately 500 psi H₂ (pressure can be approximately 350 psi). The amines were isolated and then used as amines in the reductive amination of 2-undecanene prepared from *Eriocaulon buergerianum* seed oil. The resulting β-C-glycoside 2-aminoundecane was characterized by MALDI-TOF mass spectrometry, 2D nmr, and CHN analysis. The detergency of the product was determined by fluorescence detection to determine the critical micelle concentration. The CMC values ​​of β-C-glycoside 2-aminoundecane unexpectedly ranged from 0.1 mM to 5.5 mM. Surprisingly, β-C-glycoside 2-aminoundecane exhibits antimicrobial activity against Bacillus subtilis, Pseudomonas aeruginosa, Erwinia amylovora, Escherichia coli, and Mycobacterium smegmatis. The glucose derivative showed the greatest activity against all tested Gram-positive bacteria, with a minimum inhibitory concentration (MIC) of 0.31 mM and a minimum bactericidal concentration (MIC) of 0.62 mM. The MIC against Gram-negative Erwinia and Escherichia was 0.62 mM.

[0052] All references cited in this article, including U.S. patents and U.S. patent application publications, are incorporated herein by reference in their entirety. The following references are also incorporated herein by reference: U.S. Patent 8,314,219; U.S. Patent 8,541,626.

[0053] Therefore, in view of the above, (partial) description is as follows:

[0054] A C-glycoside amine derivative as shown in the following formula:

[0055] R-CH2-C(CH3)-NH-R2

[0056] Wherein R is a glycosylated compound (e.g., as described in U.S. Patent 8,314,219) and R2 is an acyl moiety derived from any ketone of the formula R3-C(O)-R3, wherein R3 is a C1 to C22 straight-chain or branched hydrocarbon that may be saturated or unsaturated.

[0057] A composition comprising (or substantially composed of) at least one C-glycoside amine derivative represented by the following formula:

[0058] R-CH2-C(CH3)-NH-R2

[0059] Wherein R is a glycosylated compound (e.g., as described in U.S. Patent 8,314,219) and R2 is an acyl moiety derived from any ketone of the formula R3-C(O)-R3, wherein R3 is a C1 to C22 straight-chain or branched hydrocarbon, which may be saturated or unsaturated; and optionally a support.

[0060] A method for preparing C-glycoside amine derivatives as shown in the following formula:

[0061] R-CH2-C(CH3)-NH-R2

[0062] Wherein R is a glycosylated compound (e.g., as described in U.S. Patent 8,314,219) and R2 is an acyl moiety derived from any ketone of the formula R3-C(O)-R3, wherein R3 is a C1 to C22 straight-chain or branched hydrocarbon, which may be saturated or unsaturated; the method comprises (or substantially consists of): (1) reacting a glycosylated compound (e.g., glucose) C-glycosidic ketone with a catalyst (e.g., Rh), about 10 to about 25 times the excess of NH3 and an organic solvent (e.g., methanol) to form a glycosylated C-glycosidic amine, and (2) reacting the glycosylated C-glycosidic amine with a catalyst (e.g., Rh), an organic solvent (e.g., methanol) and an acyl moiety derived from any ketone of the formula R3-C(O)-R3 to form the C-glycosidic amine derivative, wherein R3 is a C1 to C22 straight-chain or branched hydrocarbon, which may be saturated or unsaturated.

[0063] The above method does not use a homogeneous catalyst (e.g., Raney nickel).

[0064] The above method does not use acyl chloride compounds.

[0065] The above method does not use the irritating solvents required for the preparation of sugar esters in known methods.

[0066] The above method does not use a long reaction time (e.g., about 48 to about 72 hours).

[0067] The term “consistent with substantially all of” excludes any additional method (or process) steps or compositional components that substantially interfere with the intended activity of the method (or process) or composition and can be readily determined by those skilled in the art (e.g., in consideration of the practice of this specification or the invention disclosed herein).

[0068] The invention disclosed herein by way of example can be practiced in the absence of any elements not specifically disclosed herein (e.g., method (or process) steps or compositional components). Thus, the specification includes a silent disclosure (“Negative Limitations in Patent Claims”, AIPLA Quarterly Journal, Tom Brody, 41(1):46-47(2013):46-47(2013): “...written support for negative limitations can also be argued by elements not excluded in the specification, referred to as silent disclosures...silence in the specification can be used to establish written descriptional support for negative limitations. For example, in Ex parteLin [No. 2009-0486, 2, 6 (BPAI May 7, 2009)], a negative limitation is added...in other words, the inventor demonstrates an example of passive compliance with a negative limitation requirement...sufficient to provide support...this case shows that the written description supports the requirement of a negative limitation. Limitations can be discovered through the disclosure of one or more embodiments that comply with the requirement of a negative limitation…”

[0069] Other embodiments of the invention will be apparent to those skilled in the art in light of this specification or the practices disclosed herein. The specification and embodiments are to be considered exemplary only, and the true scope and spirit of the invention are indicated by the appended claims.

Claims

1. A C-glycoside amine derivative as shown in the following formula: R-CH2-C(CH3)-NH-R2 Wherein R is a glycosylated compound, and R2 is a group derived by reductive amination of any ketone of formula R3-C(O)-R3 with C-glycosylamine R-CH2-C(CH3)-NH2, wherein R3 is a C1 to C22 straight-chain or branched hydrocarbon, which may be saturated or unsaturated; and wherein the glycosylated compound is selected from the group consisting of glucose, galactose, xylose, maltose, maltotriose and lactose.

2. A composition comprising at least one C-glycoside amine derivative of the following formula: R-CH2-C(CH3)-NH-R2 Wherein R is a glycosylated compound, and R2 is a group derived by reductive amination of C-glycosylamine R-CH2-C(CH3)-NH2 with any ketone of formula R3-C(O)-R3, wherein R3 is a C1 to C22 straight-chain or branched hydrocarbon, which may be saturated or unsaturated; and optionally a carrier, wherein the glycosylated compound is selected from the group consisting of glucose, galactose, xylose, maltose, maltotriose and lactose.

3. A method for preparing C-glycoside amine derivatives as shown in the following formula: R-CH2-C(CH3)-NH-R2 Wherein R is a glycosylated compound, and R2 is a group derived by reductive amination of a C-glycosidic acid R-CH2-C(CH3)-NH2 with any ketone of formula R3-C(O)-R3, wherein R3 is a C1 to C22 straight-chain or branched hydrocarbon, which may be saturated or unsaturated; the method includes: (1) reacting a glycosylated C-glycosidone with a catalyst, about 10 to about 25 times the excess of NH3 and an organic solvent to form a glycosylated C-glycosidic amine, and (2) reacting the glycosylated C-glycosidic amine with a catalyst, an organic solvent and any ketone of the formula R3-C(O)-R3 to form the C-glycosidic amine derivative, wherein R3 is a C1 to C22 straight-chain or branched hydrocarbon, which may be saturated or unsaturated, and wherein the glycosylated compound is selected from the group consisting of glucose, galactose, xylose, maltose, maltotriose and lactose.

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