Compound containing dexpanthenol

Abstract

A compound contains a chemical dexpanthenol bound to a saccharide. A corresponding compound for use in therapeutic and/or cosmetic methods is also provided. The compound may be a skincare compound or a compound configured to be used in prophylaxis of skin diseases and/or treatment of skin diseases or a compound configured to be used as a medicament for accelerating wound healing.

Claims

1. A compound, comprising a dexpanthenol chemically bonded to a saccharide.

2. The compound according to claim 1, wherein the dexpanthenol and the saccharide are chemically bonded to one another by a glycosidic bond.

3. The compound according to claim 1, wherein the saccharide is a monosaccharide.

4. The compound according to claim 3, wherein the monosaccharide is selected from the group consisting of hexoses and pentoses.

5. The compound according to claim 4, wherein the hexoses are selected from the group consisting of -glucose, -glucose, -fructose, -fructose, -galactose and -galactose, -mannose and -mannose.

6. The compound according to claim 4, wherein the pentoses are selected from the group consisting of arabinose and xylose.

7. The compound according to claim 5, wherein the -glucose is bonded to the dexpanthenol by a glycosidic bond.

8. The compound according to claim 1, wherein the compound has the following structural formula: ##STR00005##

9. The compound according to claim 1, wherein the compound is at least one of a therapeutic or cosmetic compound.

10. The compound according to claim 1, wherein the compound is a skincare compound.

11. The compound according to claim 1, wherein the compound is configured to be used in at least one of prophylaxis of skin diseases or treatment of skin diseases.

12. The compound according to claim 1, wherein the compound is configured to be used as a medicament for accelerating wound healing.

Description

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING

(1) FIG. 1 is a diagram showing an exemplary .sup.1H NMR spectrum of -glycosylated dexpanthenol;

(2) FIG. 2 is a diagram showing an exemplary .sup.13C NMR spectrum of -glycosylated dexpanthenol;

(3) FIG. 3 is a diagram showing an exemplary .sup.1H NMR spectrum of -glucosylated dexpanthenol;

(4) FIG. 4 is a diagram showing an exemplary .sup.13C NMR spectrum of -glucosylated dexpanthenol;

(5) FIG. 5 is a diagram showing an exemplary .sup.1H NMR spectrum of -galactosylated dexpanthenol;

(6) FIG. 6 is a diagram showing an exemplary .sup.13C NMR spectrum of -galactosylated dexpanthenol;

(7) FIG. 7 is a diagram showing an exemplary .sup.1H NMR spectrum of fructosylated dexpanthenol; and

(8) FIG. 8 is a diagram showing an exemplary .sup.13C NMR spectrum of fructosylated dexpanthenol.

DETAILED DESCRIPTION OF THE INVENTION

(9) (1) Preparation of -glycosylated dexpanthenol

(10) Dexpanthenol (0.05 mol/l) and sucrose (0.4 mol/l) were dissolved in 0.05 M of phosphate buffer (0.05 mol/l, pH=6) and a suspension of microorganisms (Protaminobacter rubrum Z 12 (CBS 574.77)) was added thereto.

(11) Sucrose consists of -D-glucose and -D-fructose, linked via an ,-1,2-glycosidic bond. The microorganism Protaminobacter rubrum Z 12 contains an enzyme, an -glucosidase. It catalyzes the cleavage of the sucrose used into -D-glucose and -D-fructose. During the reaction, the -D-glucose bonds chemically to the dexpanthenol.

(12) To this end, the reaction mixture is agitated in a water bath at a temperature of 37 C. After optimal product formation, the reaction is ended. The product, -glycosylated dexpanthenol, is obtained in the form of a white solid in column chromatography analysis with EE-iPrOHH.sub.2O 6:3:1 as eluent. The optimal product formation is determined by continuous sampling and thin layer chromatography.

(13) For the spectroscopic detection of the -glycosylated dexpanthenol, .sup.1H NMR and .sup.13C NMR spectra were recorded. FIG. 1 shows an exemplary .sup.1H NMR spectrum 1 of -glycosylated dexpanthenol.

(14) The .sup.1H NMR spectrum 1 was recorded at 400 MHz in deuterated methanol and the signal assignment can be found in table 1.

(15) TABLE-US-00001 TABLE 1 Signal assignment for the .sup.1H NMR spectrum 1 of -glycosylated dexpanthenol Relative Coupling constant [ppm] Assignment integral Multiplicity J [Hz] 4.76 H-1 1H Doublet 3.7 4.05 H-4 1H Singlet 3.80 H-6 1H Doublet of 11.6; 2.2 doublets 3.69-3.58 H-6b, H-3, H-1a, 6H Multiplet H-4, H-8 3.42 H-2 1H Doublet of 9.6; 3.7 doublets 3.34-3.27 3 H, H-6, H-5 3H Multiplet 3.22 H-1b 1H Doublet 9.1 1.77-1.68 2 H, H-7 2H Multiplet 1.07, 0.94 H-3a, H-3b 6H Singlet

(16) FIG. 2 shows an exemplary .sup.13C NMR spectrum 11 of -glycosylated dexpanthenol. The .sup.13C NMR spectrum 11 was recorded at 100 MHz, also in deuterated methanol. The signal assignment is listed in table 2.

(17) TABLE-US-00002 TABLE 2 Signal assignment for the .sup.13C NMR spectrum 11 of -glycosylated dexpanthenol [ppm] Assignment 176.65 C-5 100.47 C-1 76.41 C-4 76.14 C-1 75.30 C-3 73.96 C-4 73.59 C-2 71.68 C-5 62.61 C-6 60.54 C-8 39.89 C-2 37.07 C-6 33.33 C-7 22.35, 21.00 C-3a, C-3b

(18) The -glucosylated dexpanthenol is unambiguously identified from the chemical shifts found in each of the tables of the signals of the H atoms and C atoms and the integral values (for the H atoms).

(19) (2) Preparation of -glucosylated dexpanthenol

(20) Dexpanthenol (0.05 mol/l) and cellobiose (0.4 mol/l) were dissolved in sodium acetate buffer (0.05 mol/l, pH=5.2) and a -glucosidase solution (100 U in sodium acetate buffer, -glucosidase from almonds, BioChemika 49290, CAS 9001-22-3) was added thereto. Cellobiose is a disaccharide of two glucose molecules -1,4-glucosidically linked to one another. The enzyme -glucosidase enables the breakdown of cellobiose to give glucose. During the reaction, the glucose bonds chemically to the dexpanthenol.

(21) The reaction mixture is likewise agitated in a water bath at a temperature of 37 C. After optimal product formation, the reaction is ended. The product, -glucosylated dexpanthenol, is obtained in the form of a white solid in column chromatography analysis with EE-iPrOHH.sub.2O 6:3:1 as eluent.

(22) For the spectroscopic detection of the -glucosylated dexpanthenol, .sup.1H NMR and .sup.13C NMR spectra were recorded. FIG. 3 shows an exemplary .sup.1H NMR spectrum 21 of -glucosylated dexpanthenol. The glucosylation products 2a and 2b are formed in this reaction.

(23) ##STR00002##

(24) The .sup.1H NMR spectrum 21 was recorded at 400 MHz in deuterated methanol and the signal assignment can be found in the following tables 3a and 3b.

(25) TABLE-US-00003 TABLE 3a Signal assignment for the .sup.1H NMR spectrum 21 of -glucosylated dexpanthenol- linked via C-1O Relative Coupling constant [ppm] Assignment integral Multiplicity J [Hz] 4.25 H-1 1H Doublet 7.8 4.01 H-4 1H Singlet 3.83-3.89, H-6 2H Multiplet 3.63-3.67 3.61 H-8 2H Triplet 6.2 3.72, 3.44 H-1 2H Two doublets 9.1; 9.1 3.20-3.40 H-3, H-4, H-5 3H Multiplet 3.29-3.36 H-6 2H Multiplet 3.22 H-2 1H Multiplet 1.73 H-7 2H Two quintets 6.5; 2.1 1.03, 0.94 H-3a, H-3b 6H Singlet

(26) TABLE-US-00004 TABLE 3b Signal assignment for the .sup.1H NMR spectrum 21 of -glucosylated dexpanthenol - linked via C-8O Relative Coupling constant [ppm] Assignment integral Multiplicity J [Hz] 4.26 H-1 1H Doublet 7.8 3.91 H-4 1H Singlet 3.83-3.89, H-6 2H Multiplet 3.63-3.67 3.61-3.65 H-8 2H Multiplet 3.37-3.50 H-1 2H Multiplet 3.20-3.40 H-3, H-4, H-5 3H Multiplet 3.29-3.36 H-6 2H Multiplet 3.20 H-2 1H Multiplet 1.73 H-7 2H Two quintets 6.5; 2.1 1.02, 0.94 H-3a, H-3b 6H Singlet

(27) FIG. 4 shows the .sup.13C NMR spectrum 41 of -glucosylated dexpanthenol. The .sup.13C NMR spectrum 41 was recorded at 100 MHz, also in deuterated methanol. The signal assignment is listed in tables 4a and 4b.

(28) TABLE-US-00005 TABLE 4a Signal assignment for the .sup.13C NMR spectrum 41 of -glucosylated dexpanthenol - linked via C-1O [ppm] Assignment 176.15 C-5 104.72 C-1 77.11 C-1 76.06 C-4 77.95 C-3 77.93 C-4 75.01 C-2 71.57 C-5 60.56 C-8 60.52 C-6 39.91 C-2 37.03 C-6 33.19 C-7 22.34, 21.31 C-3a, C-3b

(29) TABLE-US-00006 TABLE 4b Signal assignment for the .sup.13C NMR spectrum 41 of -glucosylated dexpanthenol - linked via C-8O [ppm] Assignment 175.94 C-5 104.32 C-1 78.02 C-3 77.39 C-4 77.31 C-4 75.05 C-2 71.52 C-5 70.34 C-1 68.43 C-8 62.62 C-6 40.34 C-2 37.27 C-6 30.39 C-7 21.36, 20.83 C-3a, C-3b

(30) The -glucosylated dexpanthenol is unambiguously identified from the chemical shifts found in each of the tables of the signals of the H atoms and C atoms and the integral values (for the H atoms).

(31) (3) Preparation of -galactosylated dexpanthenol

(32) Dexpanthenol (0.05 mol/l) and lactose (0.4 mol/l) were dissolved in sodium acetate buffer (0.05 mol/l, pH=5.2) and a -galactosidase solution (100 U in sodium acetate buffer, -galactosidase from Aspergillus oryzae, Sigma G5160, CAS 9031-11-2) was added thereto. Lactose consists of D-galactose and D-glucose bonded via a -1,4-glycosidic bond. -galactosidases enzymatically catalyse the hydrolysis of this bond, with galactose being formed, which bonds chemically to the dexpanthenol during the reaction.

(33) To this end, the reaction mixture is agitated in a water bath at a temperature of 37 C. After optimal product formation, the reaction is ended. The product, -galactosylated dexpanthenol, is obtained in the form of a white solid in column chromatography analysis with EE-iPrOHH.sub.2O 6:3:1 as eluent.

(34) For the spectroscopic detection of the -galactosylated dexpanthenol, .sup.1H NMR and .sup.13C NMR spectra were recorded. FIG. 5 shows an exemplary .sup.1H NMR spectrum of -galactosylated dexpanthenol. The following galactosylation products 3a and 3b are formed in this reaction.

(35) ##STR00003##

(36) The .sup.1H NMR spectrum 51 was recorded at 400 MHz in deuterated methanol and the signal assignment can be found in the tables 5a and 5b.

(37) TABLE-US-00007 TABLE 5a Signal assignment for the .sup.1H NMR spectrum 51 of - galactosylated dexpanthenol - linked via C-1O Relative Coupling constant [ppm] Assignment integral Multiplicity J [Hz] 4.24 H-1 1H Doublet 7.8 4.05 H-4 1H Singlet 3.92-3.97 H-5 1H Multiplet 3.86-3.88 H-3 1H Multiplet 3.74-3.76 H-6 2H Multiplet 3.74-3.76, H-1 2H Multiplet 3.51-3.56 3.61 H-8 2H Triplet 6.2 3.51 H-2 1H Multiplet 3.48-3.51 H-4 1H Multiplet 3.31-3.37 H-6 2H Multiplet 1.74 H-7 2H Quintet 6.4 1.01, 0.95 H-3a, H-3b 6H Singlet

(38) TABLE-US-00008 TABLE 5b Signal assignment for the .sup.1H NMR spectrum 51 of - galactosylated dexpanthenol - linked via C-8O Relative Coupling constant [ppm] Assignment integral Multiplicity J [Hz] 4.25 H-1 1H Doublet 7.8 3.95 H-4 1H Singlet 3.92-3.97 H-5 1H Multiplet 3.86-3.88 H-3 1H Multiplet 3.74-3.76 H-6 2H Multiplet 3.63, 3.96 H-8 2H Multiplet 3.51-3.56 H-2 1H Multiplet 3.48-3.52 H-4 1H Multiplet 3.39, 3.47 H-1 2H 2 doublets 11.1; 11.4 3.35 H-6 2H Multiplet 1.83 H-7 2H Multiplet 1.01, 0.95 H-3a, H-3b 6H Singlet

(39) FIG. 6 shows the .sup.13C NMR spectrum 61 of -galactosylated dexpanthenol. The .sup.13C NMR spectrum 61 was recorded at 100 MHz, also in deuterated methanol. The signal assignment is listed in tables 6a and 6b.

(40) TABLE-US-00009 TABLE 6a Signal assignment for the .sup.13C NMR spectrum 61 of -galactosylated dexpanthenol - linked via C-1O [ppm] Assignment 176.15 C-5 105.20 C-1 77.44 C-5 76.97 C-1 76.52 C-2 76.44 C-5 76.11 C-4 70.30 C-3 62.40 C-6 60.37 C-8 39.84 C-2 37.01 C-6 33.08 C-7 22.11, 21.15 C-3a, C-3b

(41) TABLE-US-00010 TABLE 6b Signal assignment for the .sup.13C NMR spectrum 61 of -galactosylated dexpanthenol - linked via C-8O [ppm] Assignment 175.92 C-5 104.82 C-1 77.51 C-4 77.44 C-5 76.46 C-4 72.46 C-2 70.35 C-3 70.21 C-1 68.30 C-8 62.39 C-6 40.27 C-2 37.03 C-6 30.45 C-7 21.31, 21.40 C-3a, C-3b

(42) The -galactosylated dexpanthenol is unambiguously identified from the chemical shifts found in each of the tables of the signals of the H atoms and C atoms and the integral values (for the H atoms).

(43) (4) Preparation of fructosylated dexpanthenol

(44) Dexpanthenol (0.05 mol/l) and sucrose (0.4 mol/l) were dissolved in sodium acetate buffer (0.05 mol/l, pH=5.2) and a fructosidase solution (100 U in sodium acetate buffer, Boehringer Mannheim GmbH, -fructosidase from yeast, reference number 104914) was added thereto. The fructosidase solution enzymatically catalyses the cleavage of the sucrose into -D-glucose and -D-fructose. During the reaction, the -D-fructose bonds chemically to the dexpanthenol.

(45) To this end, the reaction mixture is also agitated in a water bath at a temperature of 37 C. After optimal product formation, the reaction is ended. The product, fructosylated dexpanthenol, is obtained in the form of a white solid in column chromatography analysis with EE-iPrOHH.sub.2O 6:3:1 as eluent. The product, fructosylated dexpanthenol, has the following structural formula

(46) ##STR00004##

(47) For the spectroscopic detection of the fructosylated dexpanthenol, .sup.1H NMR and .sup.13C NMR spectra were also recorded. FIG. 7 shows an exemplary .sup.1H NMR spectrum 71 of fructosylated dexpanthenol. FIG. 8 shows an exemplary .sup.13C NMR spectrum 81 of fructosylated dexpanthenol. The conjugated product of fructose and dexpanthenol is found from the signals of the spectra 71, 81. The signal assignment is found in tables 7 and 8.

(48) TABLE-US-00011 TABLE 7 Relative Coupling constant [ppm] Assignment integral Multiplicity J [Hz] 4.16 H-3 1H Doublet 8.9 4.03 H-4 1H Singlet 4.00 H-4 1H Triplet 8.9 3.76 H-5 1H Multiplet 3.61 H-1, H-6, H-8 6H Multiplet 3.47 H-1 2H Multiplet 3.34 H-6 2H Multiplet 1.73 H-7 2H Multiplet 1.07 H-3 6H Singlet

(49) TABLE-US-00012 TABLE 8 [ppm] Assignment 175.65 C-5 104.43 C-2 83.52 C-5 80.07 C-3 77.44 C-4 76.67 C-4 77.44 C-4 68.40 C-1 64.17 C-6 63.80 C-1 60.59 C-8 39.13 C-2 37.03 C-6 33.14 C-7 20.74 2 C-3

(50) The fructosylated dexpanthenol is unambiguously identified from the chemical shifts found in each of the tables 7 and 8 of the signals of the H atoms and C atoms and the integral values (for the H atoms).

(51) The following is a summary list of reference numerals and the corresponding structure used in the above description of the invention:

LIST OF REFERENCE NUMERALS

(52) 1 .sup.1H NMR spectrum of -glucosylated dexpanthenol 11 .sup.13C NMR spectrum of -glucosylated dexpanthenol 21 .sup.1H NMR spectrum of -glucosylated dexpanthenol 41 .sup.13C NMR spectrum of -glucosylated dexpanthenol 51 .sup.1H NMR spectrum of -galactosylated dexpanthenol 61 .sup.13C NMR spectrum of -galactosylated dexpanthenol 71 .sup.1H NMR spectrum of -fructosylated dexpanthenol 81 .sup.13C NMR spectrum of -fructosylated dexpanthenol