Uses of ursolic acid saponin and oleanolic acid saponin in preparing medicine for increasing white blood cell and/or blood platelet

Abstract

The invention provides an application of ursolic acid saponin and oleanolic acid saponin with a general formula I in the preparation of medicines for increasing leucocyte and/or blood platelet. The invention also provides a medicine combination with the chemical compound. The invention adopts the low-cost ursolic acid and oleanolic acid which is easily available from natural products and introduces monosaccharide and oligosaccharyl through structure modification. Pharmacology experiments prove that the invention can notably increase the leucocyte and/or the blood platelet.

Description

technical field

[0001] The invention belongs to the technical field of medicines. Specifically, it relates to the application of ursolic acid saponin and oleanolic acid saponin in the preparation of medicines for increasing white blood cells and / or platelets. Background technique

[0002] White blood cells have the ability to phagocytose, can eliminate foreign pathogenic bacteria, and protect the health of the body, so people call it the body guard. The leukocytes in the blood circulation of normal people are 4000-10000 / m3. The most important white blood cells are neutrophils with defensive functions, accounting for 50-70% of the total. Generally speaking, the most common and most important leukopenia refers to neutropenia. When the total number of white blood cells is lower than 4000 / mm3, the body's resistance is low at this time, and it is extremely easy to cause bacterial infection, which is life-threatening in severe cases. Platelets are one of the formed components ...

Examples

Embodiment 1

[0059] Example 1: Preparation of 3-O-(α-L-arabinopyranose) ursolic acid-28-O-(α-L-arabinopyranose) ester:

[0060] Ursolic acid 1g (2.2mmol) in 20ml dry CH 2 Cl 2 solution, N 2 Under atmosphere, with arabinose glycosylation donor 2,3,4-tri-O-benzoyl-β-L-arabinosyl trichloroacetimidate 3.4g (5.7mmol, 2.6eq) ( The synthesis method of this compound refers to J.Org.Chem.1999, 64, 7265-7266), after mixing 1.5 g of powdered 4 angstrom molecular sieves, trimethylsilyl trifluoromethanesulfonate TMSOTf (0.03 ml, 0.15eq), the reaction was gradually warmed to room temperature, stirred overnight, and a small amount of Et was added 3 N (0.3ml) quenched the reaction, filtered, and after the filtrate was concentrated, silica gel column chromatography was eluted with petroleum ether / ethyl acetate system (4 / 1-2 / 1) to obtain 1.47g (1.1 mmol), it was dissolved in methanol / dichloromethane (2 / 1, 30ml) and 378mgNaOMe (7mmol, 6.4eq) was added, reacted at room temperature for 4 hours, acidic resi...

Embodiment 2

[0066] Example 2: Preparation of 3-O-(α-L-rhamnopyranose) ursolic acid-28-O-(α-L-rhamnopyranose) ester:

[0067] Similar to the method of Example 1, 2,3,4-tri-benzoyl-β-L-rhamnopyranosyl trichloroacetimidate is the glycosylation donor, and 3-O-(α -L-rhamnopyranosyl)ursolic acid-28-O-(α-L-rhamnopyranosyl)ester. [ α ] D 20 = - 11.8 ( C 0.17 , DMF )

[0068] 1 HNMR (600MHz, d 5 -pyridine): δppm 6.75 (1H, s), 5.46 (1H, m), 5.32 (1H, s), 4.56-4, 57 (2H, m), 4.52 (1H, dd, J=9.12, 3.2Hz) , 4.47 (1H, dd, J = 8.9, 3.2Hz), 4.38 (1H, t, J = 9.3Hz), 4.29-4.34 (3H, m), 3.17 (H, dd, J = 11.8, 4.44Hz), 2.44(1H, d, J=11.3Hz), 1.81(1H, m), 1.70(3H, d, J=6Hz), 1.67(3H, d, J=6Hz), 1.17(3H, s), 1.08( 1H, m), 0.93(3H, s), 0.92(6H, s), 0.90(3H, d, J=6.4Hz), 0.88(3H, d, J=6.4Hz), 0...

Embodiment 3

[0071] Example 3: Preparation of 3-O-(β-D-glucopyranose) ursolic acid-28-O-(β-D-glucopyranose) ester:

[0072] Similar to the method of Example 1, the glycosylation donor is 2,3,4,6-tetra-O-benzoyl-α-D-glucosyl trichloroacetimidate, and 3-O-(β -D-glucopyranose)ursolic acid-28-O-(β-D-glucopyranose) ester. [ α ] D 20 = + 21.7 ( C 1.02 , MeOH )

[0073] IR(KBr)cm -1 : 3417, 2925, 1727, 1672, 1456, 1377, 1226, 1075, 1027, 896, 831

[0074] 1 HNMR (600MHz, CD 3 OD): δppm5.33 (d, J=8.3Hz, 1H, H-1″), 5.24 (t, 1H, H-12), 4.31 (d, J=7.8Hz, 1H, H-1′), 3.77-3.84(m, 2H), 3.65-3.68(m, 2H), 3.28--3.39(m, 7H), 3.16-3.18(m, 2H), 2.22(d, J=11.2Hz, 1H, H- 18), 1.12, 1.05, 0.96, 0.84, 0.83(s each, 3Heach, Me×5), 0.88(d, J=6.4Hz, 3H), 0.78(d, J=11.6Hz, 1H, H-5)

[0075] 13 CN...

technical field

[0001] The invention belongs to the technical field of medicines. Specifically, it relates to the application of ursolic acid saponin and oleanolic acid saponin in the preparation of medicines for increasing white blood cells and / or platelets. Background technique

[0002] White blood cells have the ability to phagocytose, can eliminate foreign pathogenic bacteria, and protect the health of the body, so people call it the body guard. The leukocytes in the blood circulation of normal people are 4000-10000 / m3. The most important white blood cells are neutrophils with defensive functions, accounting for 50-70% of the total. Generally speaking, the most common and most important leukopenia refers to neutropenia. When the total number of white blood cells is lower than 4000 / mm3, the body's resistance is low at this time, and it is extremely easy to cause bacterial infection, which is life-threatening in severe cases. Platelets are one of the formed components ...

Examples

Embodiment 1

[0059] Example 1: Preparation of 3-O-(α-L-arabinopyranose) ursolic acid-28-O-(α-L-arabinopyranose) ester:

[0060] Ursolic acid 1g (2.2mmol) in 20ml dry CH 2 Cl 2 solution, N 2 Under atmosphere, with arabinose glycosylation donor 2,3,4-tri-O-benzoyl-β-L-arabinosyl trichloroacetimidate 3.4g (5.7mmol, 2.6eq) ( The synthesis method of this compound refers to J.Org.Chem.1999, 64, 7265-7266), after mixing 1.5 g of powdered 4 angstrom molecular sieves, trimethylsilyl trifluoromethanesulfonate TMSOTf (0.03 ml, 0.15eq), the reaction was gradually warmed to room temperature, stirred overnight, and a small amount of Et was added 3 N (0.3ml) quenched the reaction, filtered, and after the filtrate was concentrated, silica gel column chromatography was eluted with petroleum ether / ethyl acetate system (4 / 1-2 / 1) to obtain 1.47g (1.1 mmol), it was dissolved in methanol / dichloromethane (2 / 1, 30ml) and 378mgNaOMe (7mmol, 6.4eq) was added, reacted at room temperature for 4 hours, acidic resi...

Embodiment 2

[0066] Example 2: Preparation of 3-O-(α-L-rhamnopyranose) ursolic acid-28-O-(α-L-rhamnopyranose) ester:

[0067] Similar to the method of Example 1, 2,3,4-tri-benzoyl-β-L-rhamnopyranosyl trichloroacetimidate is the glycosylation donor, and 3-O-(α -L-rhamnopyranosyl)ursolic acid-28-O-(α-L-rhamnopyranosyl)ester. [ α ] D 20 = - 11.8 ( C 0.17 , DMF )

[0068] 1 HNMR (600MHz, d 5 -pyridine): δppm 6.75 (1H, s), 5.46 (1H, m), 5.32 (1H, s), 4.56-4, 57 (2H, m), 4.52 (1H, dd, J=9.12, 3.2Hz) , 4.47 (1H, dd, J = 8.9, 3.2Hz), 4.38 (1H, t, J = 9.3Hz), 4.29-4.34 (3H, m), 3.17 (H, dd, J = 11.8, 4.44Hz), 2.44(1H, d, J=11.3Hz), 1.81(1H, m), 1.70(3H, d, J=6Hz), 1.67(3H, d, J=6Hz), 1.17(3H, s), 1.08( 1H, m), 0.93(3H, s), 0.92(6H, s), 0.90(3H, d, J=6.4Hz), 0.88(3H, d, J=6.4Hz), 0...

Embodiment 3

[0071] Example 3: Preparation of 3-O-(β-D-glucopyranose) ursolic acid-28-O-(β-D-glucopyranose) ester:

[0072] Similar to the method of Example 1, the glycosylation donor is 2,3,4,6-tetra-O-benzoyl-α-D-glucosyl trichloroacetimidate, and 3-O-(β -D-glucopyranose)ursolic acid-28-O-(β-D-glucopyranose) ester. [ α ] D 20 = + 21.7 ( C 1.02 , MeOH )

[0073] IR(KBr)cm -1 : 3417, 2925, 1727, 1672, 1456, 1377, 1226, 1075, 1027, 896, 831

[0074] 1 HNMR (600MHz, CD 3 OD): δppm5.33 (d, J=8.3Hz, 1H, H-1″), 5.24 (t, 1H, H-12), 4.31 (d, J=7.8Hz, 1H, H-1′), 3.77-3.84(m, 2H), 3.65-3.68(m, 2H), 3.28--3.39(m, 7H), 3.16-3.18(m, 2H), 2.22(d, J=11.2Hz, 1H, H- 18), 1.12, 1.05, 0.96, 0.84, 0.83(s each, 3Heach, Me×5), 0.88(d, J=6.4Hz, 3H), 0.78(d, J=11.6Hz, 1H, H-5)

[0075] 13 CN...

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