CN104119420A - Dioscin glycosylated derivative and preparation method and application thereof - Google Patents
Dioscin glycosylated derivative and preparation method and application thereof Download PDFInfo
- Publication number
- CN104119420A CN104119420A CN201310147606.3A CN201310147606A CN104119420A CN 104119420 A CN104119420 A CN 104119420A CN 201310147606 A CN201310147606 A CN 201310147606A CN 104119420 A CN104119420 A CN 104119420A
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- CN
- China
- Prior art keywords
- dioscin
- glycosylated derivative
- preparation
- base
- glycosylated
- Prior art date
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- VNONINPVFQTJOC-ZGXDEBHDSA-N dioscin Chemical compound O([C@@H]1[C@@H](CO)O[C@H]([C@@H]([C@H]1O)O[C@H]1[C@@H]([C@H](O)[C@@H](O)[C@H](C)O1)O)O[C@@H]1CC2=CC[C@H]3[C@@H]4C[C@H]5[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@@H]([C@]1(OC[C@H](C)CC1)O5)C)[C@@H]1O[C@@H](C)[C@H](O)[C@@H](O)[C@H]1O VNONINPVFQTJOC-ZGXDEBHDSA-N 0.000 title claims abstract description 30
- HDXIQHTUNGFJIC-UHFFFAOYSA-N (25R)-spirost-5-en-3beta-ol 3-O-<O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside> Natural products O1C2(OCC(C)CC2)C(C)C(C2(CCC3C4(C)CC5)C)C1CC2C3CC=C4CC5OC1OC(CO)C(O)C(O)C1OC1OC(C)C(O)C(O)C1O HDXIQHTUNGFJIC-UHFFFAOYSA-N 0.000 title claims abstract description 27
- VNONINPVFQTJOC-RXEYMUOJSA-N Collettiside III Natural products O([C@@H]1[C@@H](O)[C@H](O[C@H]2[C@H](O)[C@H](O)[C@@H](O)[C@H](C)O2)[C@H](CO)O[C@@H]1O[C@@H]1CC=2[C@@](C)([C@@H]3[C@H]([C@H]4[C@@](C)([C@H]5[C@H](C)[C@@]6(O[C@H]5C4)OC[C@H](C)CC6)CC3)CC=2)CC1)[C@H]1[C@H](O)[C@H](O)[C@@H](O)[C@H](C)O1 VNONINPVFQTJOC-RXEYMUOJSA-N 0.000 title claims abstract description 27
- CJNUQCDDINHHHD-APRUHSSNSA-N dioscin Natural products C[C@@H]1CC[C@@]2(OC1)O[C@H]3C[C@H]4[C@@H]5CC=C6C[C@H](CC[C@@H]6[C@H]5CC[C@]4(C)[C@H]3[C@@H]2C)O[C@@H]7O[C@H](CO)[C@@H](O[C@@H]8O[C@@H](C)[C@H](O)[C@@H](O)[C@H]8O)[C@H](O)[C@H]7O[C@@H]9O[C@@H](C)[C@H](O)[C@@H](O)[C@H]9O CJNUQCDDINHHHD-APRUHSSNSA-N 0.000 title claims abstract description 27
- VNONINPVFQTJOC-UHFFFAOYSA-N polyphyllin III Natural products O1C2(OCC(C)CC2)C(C)C(C2(CCC3C4(C)CC5)C)C1CC2C3CC=C4CC5OC(C(C1O)OC2C(C(O)C(O)C(C)O2)O)OC(CO)C1OC1OC(C)C(O)C(O)C1O VNONINPVFQTJOC-UHFFFAOYSA-N 0.000 title claims abstract description 27
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
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- WQLVFSAGQJTQCK-UHFFFAOYSA-N diosgenin Natural products CC1C(C2(CCC3C4(C)CCC(O)CC4=CCC3C2C2)C)C2OC11CCC(C)CO1 WQLVFSAGQJTQCK-UHFFFAOYSA-N 0.000 claims description 18
- WQLVFSAGQJTQCK-VKROHFNGSA-N diosgenin Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CC[C@H](O)CC4=CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 WQLVFSAGQJTQCK-VKROHFNGSA-N 0.000 claims description 17
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- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 2
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- 125000003147 glycosyl group Chemical group 0.000 description 5
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
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- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
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Landscapes
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明提供了通式Ⅰ所示的薯蓣皂苷糖基化衍生物，R为戊糖基或乳糖基。本发明还提供了该类衍生物的制备方法和用途。经实验研究表明，本发明的薯蓣皂苷糖基化衍生物，不仅具有良好的抗肿瘤活性，还具有皮肤保湿活性，为抗癌药物或功能性化妆品的制备提供了新的选择。 The present invention provides dioscin glycosylated derivatives represented by general formula I, R is pentosyl or lactosyl. The invention also provides the preparation method and application of the derivatives. Experimental studies show that the dioscin glycosylated derivatives of the present invention not only have good antitumor activity, but also have skin moisturizing activity, which provides a new option for the preparation of anticancer drugs or functional cosmetics.
Description
Technical field
The present invention relates to dioscin glycosylated derivative and its production and use, belong to pharmaceutical field.
Background technology
Diosgenin is one of at present known important steroidal saponin aglycon, and multi-source is in yams such as Rhizome of Peltate Yam, Dioscorea nipponica Mak. Ningpo Yam Rhizome, Dioscorea panthaica Prain et Burkill, Rhizoma Curcumae Longaes, and its structural formula is as follows
Dioscin analogue refers to take the saponins that diosgenin is aglycon.In natural saponin(e, C-3 position is many is connected with glycosyl, and its glycosyl is the sugar chain by 3-6 monosaccharide composition mostly, and is glycosyl mainly with hexose or disaccharides, trisaccharide etc.In recent years, development along with separation and extraction technology, multiple dioscin is separated, studies show that take the physiological function, the particularly effect at aspects such as antitumor, immunomodulatory, anti-inflammatory, reducing blood-fat, anti-AIDS, prevention and cure of cardiovascular diseases that steroidal saponin that glycosyl is conjugate has a multiple uniqueness is more and more subject to people's attention.
The triangle leaf saponin(e (Deltonin) extracting from yellow ginger is a kind of dioscin compounds, the IC to colon cancer cell
50value is less than 2.5 μ molL
-1.When administration concentration is 2 μ molL
-1time, to the inhibiting rate of colon cancer cell, be 88.24%, higher than the inhibiting rate 57.97% of 5-Fluorouracil under same condition.In recent years the caudaside OSW-1 finding has good antitumour activity, and has entered clinical experiment.
Along with people are to the understanding in depth and the increase day by day of this compounds usage quantity of saponins compound, develop the new dioscin glycosylated derivative with good biological activity, have a good application prospect.
Summary of the invention
Technical program of the present invention lies in providing a kind of new dioscin glycosylated derivative, and the simple and effective method of preparing dioscin glycosylated derivative, and the purposes of this analog derivative is provided.
Particularly, the invention provides the dioscin glycosylated derivative shown in formula I:
R is pentose base or lactose base.
Further, described pentose base is D/L-ribosyl, D/L-aralino, 2-deoxyribosyl base or 5-deoxyribosyl.
Preferably, described dioscin glycosylated derivative is
The present invention also provides a kind of method of preparing above-mentioned dioscin glycosylated derivative, and it comprises following operation steps:
(1) get pentose or lactose, by acylation reaction, prepare the carbohydrate intermediate of full acidylate protection;
(2) get the carbohydrate intermediate that diosgenin, step (1) prepare, directly carry out after glycosylation reaction, under alkaline environment, deprotection base, prepares target compound.
Described pentose is selected from D/L-ribosyl, D/L-aralino, 2-deoxyribosyl, 5-ribodesose.
Further, in step (1), adopt acetic anhydride as acetylizing agent, pyridine or sodium acetate are made catalyzer; In step (2), using tin tetrachloride or trifluoromethanesulfonic acid trimethylsilyl group as catalyzer, carry out glycosylation reaction; In step (2), alkaline environment is 0.1-0.5mol/L NaOCH
3/ CH
3oH solution room temperature environment.
Above-mentioned preparation method, has simplified reactions steps greatly, has shortened the reaction times, for the industrialization of dioscin compounds, prepares feasibility is provided.
The present invention also provides the above-mentioned dioscin glycosylated derivative purposes in preparing Moisturizer.
The present invention also provides a kind of Moisturizer, and it is to be activeconstituents by above-mentioned dioscin glycosylated derivative, adds the external preparation that conventional auxiliary material is prepared from.
The present invention also provides the above-mentioned dioscin glycosylated derivative purposes in preparing anti-tumor drug.
Further, described medicine is the medicine for the treatment of mammary cancer.
Through experimental study, show, dioscin glycosylated derivative of the present invention, not only has good anti-tumor activity, also has skin moisture-keeping activity, for the preparation of cancer therapy drug or functional cosmetics provides new selection.
Obviously, according to foregoing of the present invention, according to ordinary skill knowledge and the customary means of this area, not departing under the above-mentioned basic fundamental thought of the present invention prerequisite, can also make modification, replacement or the change of other various ways.
The embodiment of form, is described in further detail foregoing of the present invention again by the following examples.But this should be interpreted as to the scope of the above-mentioned theme of the present invention only limits to following example.All technology realizing based on foregoing of the present invention all belong to scope of the present invention.
Embodiment
The preparation of embodiment 1 diosgenin β-D-galactopyranose base-(1 → 4)-β-D-glucopyranoside
In reaction flask, add successively 4A molecular sieve (2.5g), CH
3cOONa(0.74g, 9mmol), anhydrous acetic acid acid anhydride (15ml, about 158mmol), under stirring, progressively heat up, add lactose (2.55g, 7.5mmol) in batches, in reaction process, control temperature of reaction and be no more than 110 ° of C.TLC detects, termination reaction after about 3.5h, and it is yellow that reaction solution is.Under stirring, reaction solution is slowly poured in 200ml frozen water, in whipping process, syrupy shape mucus is progressively solidified, and becomes powdery white solid, filters, and collects solid precipitate.Filtrate, through dichloromethane extraction, eliminates solvent, obtains yellow syrup, and liquid syrup is with dissolving under appropriate ethanol heated condition, then pours in frozen water, and adularescent solid is separated out again.Merge gained white solid twice, use successively frozen water, saturated sodium bicarbonate aqueous solution, frozen water, 50% washing with alcohol, compound 1, productive rate 85.2%.ESIMS?Calcd?for?C
28H
38O
19[M+Na]:701.60。
Compound 1 679mg(1mmol), diosgenin 414mg(1mmol), anhydrous ClCH
2cH
2cl/CH
3cN mixed solution 30ml(v:v 1:1), ice-water bath is chilled to 0 ° of C, adds rapidly 100 μ lSnCl
4, after ten minutes, remove ice-water bath, rise under room temperature and react.TLC detects, until reaction is not being carried out.Frozen water washing 3 times, through anhydrous Na
2sO
4dry, silica gel column chromatography is separated, obtains white solid compound 1a.
1H?NMR(400MHz,CDCl
3)δ5.37(d,J=2.3Hz,2H),5.22(t,J=9.3Hz,1H),5.13(t,1H),4.97(dd,J=10.4,3.2Hz,1H),4.89(t,J=8.8Hz,1H),4.57(d,J=8.0Hz,1H),4.53–4.38(m,3H),4.20–4.06(m,3H),3.90(d,J=6.8Hz,1H),3.80(t,J=9.4Hz,1H),3.61(dd,J=9.3,4.2Hz,1H),3.54–3.34(m,3H),2.18(s,3H),2.13(s,3H),2.08(d,J=6.8Hz,12H),1.99(s,3H),1.04–0.97(m,6H),0.81(d,J=6.3Hz,6H);
13C?NMR(100MHz,CDCl
3)δ169.37,169.34,169.14,169.05,168.83,168.60,168.05,139.32,120.86,108.28,100.04,98.44,79.78,79.01,75.37,71.88,71.52,70.81,69.98,69.65,68.10,65.83,65.60,61.07,59.81,55.46,49.03,40.59,39.24,38.72,37.88,36.12,35.82,31.05,30.82,30.38,29.28,28.41,27.78,19.88,19.82,19.74,19.62,19.50,18.35,16.12,15.26,13.51;HR-MS(m/z)calculated?for?C
53H
76O
20:1055.4828[M+Na]
+,observed:1055.4830[M+Na]
+。
In the white solid compound of above-mentioned gained, add 5ml0.1mol/L NaOCH
3/ CH
3oH solution, compound can not dissolve completely, supersound process 1 minute, silica gel column chromatography is separated, obtains compound diosgenin β-D-galactopyranose base-(1 → 4)-β-D-glucopyranoside (2).
1H?NMR(400MHz,pyridine-d
5)δ7.55(s,1H),7.26(s,1H),6.98(s,1H),6.63(d,J=16.1Hz,2H),6.49(s,1H),6.21(s,1H),5.30(d,J=5.0Hz,1H),5.15(d,J=7.8Hz,1H),5.01(d,J=7.8Hz,1H),5.00–4.94(m,2H),4.66–4.47(m,6H),4.46–4.39(m,1H),4.39–4.30(m,2H),4.23–4.13(m,2H),4.13–4.04(m,1H),3.99–3.84(m,2H),3.65–3.57(m,1H),3.51(t,J=10.5Hz,1H),2.70(dd,J=13.4,2.6Hz,1H),2.46(t,J=12.2Hz,1H),2.10(d,J=11.7Hz,1H),1.15(d,J=6.9Hz,3H),0.91(s,3H),0.84(s,3H),0.70(d,J=5.5Hz,3H);
13C?NMR(100MHz,pyridine-d
5)δ141.32,122.18,109.72,106.35,102.75,82.76,81.55,78.68,77.72,77.25,76.87,75.69,75.36,72.96,70.55,67.31,63.34,62.77,62.51,57.09,50.71,42.42,40.91,40.32,39.72,37.89,37.49,32.71,32.65,32.27,32.08,31.06,30.66,29.72,21.57,19.85,17.79,16.82,15.50;HR-MS(m/z)calculated?for?C
39H
62O
13:761.4088[M+Na]
+,observed:761.4081[M+Na]
+。
The preparation of embodiment 2 diosgenin ribosides (3) and diosgenin 5 '-desoxyriboside (4)
1a:R
1=R
2=R
3=OAc,2a：R
1=R
2=OAc,R
3=H
1b:R
1=R
2=R
3=OAc,2b：R
1=R
2=OAc,R
3=H
1c:R
1=R
2=R
3=OH（3），2c：R
1=R
2=OH,R
3=H?（4）
It is anhydrous 1 that 3g(7.25mmol) diosgenin is dissolved in 150ml, in 2-ethylene dichloride, adds compound a (7.25mmol) to be placed in ice bath and stir 5 minutes, adds anhydrous stannic chloride 200 μ l, the about 1.5h of stirring at room after 5-10min.Except after desolventizing, be dissolved in CH
2cl
2in, respectively through NaHCO
3solution, frozen water washing, anhydrous Na
2sO
4dry, revolve steaming solvent, obtain crude product, silica gel column chromatography separation obtains compound b.
Compound 1b,
1hNMR (400MHz; CDCl
3): 5.33-5.36 (2H, m), 5.16-5.23 (2H, m), 4.34-4.43 (1H, m, H-16), 4.24-4.27 (2H, m), 4.10-4.14 (1H, m), 3.46-3.51 (2H, m), 3.35-3.40 (1H, m), 0.96-1.01 (7H, m), 0.79 (6H, d, J=5.5Hz).
13cNMR (100MHz; CDCl
3; Me
4si): 170.64,169.71,169.68,140.31,121.76,109.28,103.32,80.82,78.17,75.23,71.76,66.85,64.92,62.11,56.51,50.06,41.62,40.28,39.77,38.38,37.16,36.87,32.08,31.86,31.41,30.31,29.48,28.82,20.84,20.65,20.55,19.37,17.15,16.29,14.53.HRMS (ESI): m/z calcd for C
38h
56o
10+ Na
+: 695.3771[M+Na
+]; Found:695.3771;
Compound 2b
1hNMR (400MHz; CDCl
3): 5.33 (1H, d, J=5.1Hz), 5.17 (1H, d, J=5.0Hz), 5.11-5.14 (2H, m), 4.41 (1H, q, J=7.2Hz), 4.12-4.19 (1H, m), (3.46-3.51 2H, m), 3.35-3.40 (1H, m), (1.01 3H, s), 0.97 (3H, d, J=6.9Hz), 0.79 (6H, d, J=4.2).
13cNMR (100MHz; CDCl
3): 170.25,169.32,140.11,121.29,108.88,103.00,80.42,77.68,77.21,74.85,71.28,66.45,64.41,61.70,56.10,49.62,41.21,39.87,39.61,39.37,36.53,36.41,31.66,31.45,31.00,29.91,28.41,27.37,20.46,20.44,20.26,20.16,18.97,16.75,15.89,14.14.HRMS (ESI): m/zcalcd for C
36h
54o
6+ H
+: 615.3897[M+H
+]; Found:615.3900.
Deprotection: compound b(1.5mmol) add sodium methylate-methanol solution, stir after 15min, acetic acid-methanol solution is adjusted pH7-8.Suction filtration, methyl alcohol obtains target chemical combination C after washing.
Compound 3,
1hNMR (400MHz; d
6-DMSO): 5.33 (1H, d, J=4.0Hz, H-6), 4.97 (1H, d, J=4.5Hz), 4.87 (1H, s), 4.79 (1H, d, J=6.7Hz), 4.58 (1H, t, 5.6Hz), 4.25-4.31 (1H, m, H-16), 3.47-3.52 (1H, m), 3.39-3.34 (1H, m), 3.21 (1H, t, J=10.8Hz), 0.90-0.95 (7H, m), 0.74 (6H, s).
13cNMR (150MHz; d
6-DMSO): 141.15,121.38,108.90,105.43,83.95,80.68,76.04,5.15,71.61,66.40,62.29,56.25,50.01,41.58,40.43,39.59,36.83,32.01,31.95,31.47,31.42,30.30,28.96,27.99,20.87,19.56,17.58,16.49,15.14.HRMS (ESI): m/z calcd for C
32h
50o
7+ Na
+: 569.3454[M+Na
+]; Found:569.3438;
Compound 4,
1hNMR (400MHz; CDCl
3): 5.33 (1H, d, 4.8Hz), 5.04 (1H, s), 4.40 (1H, q, J=6.8Hz, H-16), 3.99 (3H, m), 3.46-3.51 (1H, m), 3.36 (1H, t, J=10.8Hz), 1.00 (3H, s), 0.97 (6H, d, J=6.8Hz).
13cNMR (100MHz; CDCl
3): 140.49,121.64,109.36,105.30,80.88,79.22,76.47,75.91,66.68,62.12,56.51,50.10,41.65,40.29,39.79,38.70,36.92,32.11,31.87,31.47,31.40,30.30,29.69,28.81,20.85,20.36,19.37,17.13,16.28,14.50.HRMS (ESI): m/z calcd for C
32h
50o
7+ Na
+: 531.3686[M+Na
+]; Found:531.3672.
The preparation of embodiment 3 diosgenin β-2-deoxyribosyl glucosides (5) and diosgenin α-2-deoxyribosyl glucosides (6)
Tol=is to methyl benzoyl
Compound c prepares reference: Val é rie Rolland, Mitsuharu Kotera, Jean Lhomme.Synthetic Communications.1997,27 (20): 3505-3511.
By 2.9g(7mmol) diosgenin is dissolved in 1; in the mixing liquid of 2-ethylene dichloride and acetonitrile (3:2), add 3.0g (7mmol) 1-chloro-3, after bis-pairs of methyl benzoyl-2-deoxyribosyls of 5-; ice bath 5min, adds 250 μ L catalyzer trifluoromethanesulfonic acid trimethylsilyl groups.Stir about 5min is placed on room temperature reaction, and TLC adds a small amount of saturated sodium bicarbonate solution termination reaction after detecting and having reacted to saccharide donor.Vacuum hangs after organic solvent, add dichloromethane solution dilution, then, with saturated sodium bicarbonate solution washing 2 times, wash after 1 time, collect organic phase and obtain crude product with being spin-dried for after anhydrous sodium sulfate drying to collect, with silica gel column chromatography separating-purifying to product 1d and 2d.
Diosgenin 3, bis-pairs of methyl benzoyl β-2-deoxyribosyl glucosides of 5-(1d),
1hNMR (400MHz, CDCl
3): δ 7.94 (dd, J=21.9,8.1Hz, 4H); 7.33～7.14 (m, 4H), 5.59 (t, 1H); 5.56～5.48 (m, 1H), 5.33 (s, 1H); 4.56～4.45 (m, 3H), 4.40 (dd, J=7.7Hz; 1H), 3.59～3.43 (m, 2H), 3.37 (t; J=10.9Hz, 1H), 2.57～2.46 (m, 1H); 2.40 (d, J=6.7Hz, 6H), 2.38～2.30 (m; 2H), 2.16 (t, J=11.4Hz, 1H); 0.97 (d, J=4.3Hz, 6H); 0.79 (d, J=6.8Hz, 6H);
13cNMR (100MHz, DMSO-d
6): δ 166.33,166.08, and 143.96,143.65,140.74,129.84,129.71; 129.10,129.04,127.21,126.98,121.41,109.27,102.83; 81.67,80.82,76.81,75.84,66.84,65.28,62.11; 56.50,50.05,41.61,40.26,39.77,39.54,38.65; 37.21,36.88,32.08,31.85,31.42.31.39,30.30,29.66; 28.81,21.67,20.80,19.33,17.14,16.27,14.52; HRMS (ESI): m/z calcd for C
48h
62o
8+ Na
+: 789.4342[M+Na
+]; Found:789.4341.
Diosgenin 3, bis-pairs of methyl benzoyl α-2-deoxyribosyl glucosides of 5-(2d),
1hNMR (400MHz, CDCl
3): δ 7.93 (dd, J=15.4,8.1Hz, 4H); 7.28～7.19 (m, 4H), 5.46 (d, J=4.9Hz; 1H), 5.44～5.37 (m, 1H), 5.32 (s; 1H), 4.64～4.46 (m, 3H), 4.41 (dd; J=14.9,7.4Hz, 1H), 3.61～3.43 (m; 2H), 3.38 (t, J=10.9Hz, 1H); 2.60～2.47 (m, 1H), 2.41 (d, J=5.2Hz; 6H), 2.16 (d, J=14.1Hz, 1H); (1.03 s, 3H), 0.97 (d, J=6.9Hz; 3H), 0.79 (d, J=4.2Hz, 6H);
13cNMR (100MHz, CDCl
3): δ 166.43,166.28, and 143.87,143.75,140.92,129.81,129.71,129.10,129.08,127.19,127.13,121.37,109.27,101.68,80.82,80.66,76.21,74.62,66.84,64.37,62.11,56.49,50.04,41.61,40.38,40.26,39.77,39.56,37.11,36.88,32.08,31.86,31.45,31.40,30.30,28.81,27.93,21.67,20.84,19.34,17.14,16.29,14.50; HRMS (ESI): (m/z) calcd for C
48h
62o
8+ Na
+: 789.4342[M+Na
+]; Found:789.4342.
Deprotection: compound 1d or 2d(1.5mmol) add sodium methylate-methanol solution, stir after 15min, acetic acid-methanol solution is adjusted pH7-8, and suction filtration, obtains compound 5 and compound 6.
Diosgenin β-2-deoxyribosyl glucosides (5),
1hNMR (400MHz, CDCl3): δ 5.41 (d, J=5.1Hz, 1H), 5.32 (d; J=4.1Hz, 1H), 4.53 (s, 1H), 4.39 (dd; J=15.0,7.3Hz, 1H), 4.04 (d, J=3.0Hz; 1H), 3.69 (t, J=16.3Hz, 2H), 3.54～3.41 (m; 2H), 3.36 (t, J=10.9Hz, 1H), 2.95 (s; 1H), 2.61 (d, J=33.2Hz, 1H);
13cNMR (100MHz, CDCl3): δ 140.34,121.77,109.31,102.69, and 87.74; 80.82,76.71,72.45,66.85,63.44; 62.08,56.46,50.03,43.27,41.61; 40.26,39.19,36.86,32.06,31.84; 31.41,31.38,30.29,29.78,28.79; 20.83,19.36,17.14,16.28,14.52; HRMS (ESI): m/zcalcd for C32H50O6+Na+:553.3505[M+Na+]; Found:553.3528.
Diosgenin α-2-deoxyribosyl glucosides (6),
1hNMR (400MHz, CDCl3): δ 5.40 (d, J=4.0Hz, 1H), 5.36 (d; J=4.4Hz, 1H), 4.40 (dd, J=15.0; 7.4Hz, 1H), 4.21～4.11 (m, 2H); 3.77～3.67 (m, 1H), 3.65～3.43 (m, 4H); (3.37 t, J=10.9Hz, 1H), 2.99 (d; J=11.2Hz, 1H), 2.42～2.22 (m, 2H);
13cNMR (100MHz, CDCl3): δ 140.80,121.63,121.41,109.28, and 102.26,87.54,80.81,76.35,73.12,71.70,66.84,63.22,62.09,56.52,50.05,42.26,41.84,41.60,40.40,40.26,39.78,37.22,37.04,36.83,36.64,32.04,31.84,31.61,31.43,31.38,30.29,28.79,27.83,20.86,19.41,19.37,17.13,16.27,14.51; HRMS (ESI): m/z calcd for C32H50O6+Na+:553.3505[M+Na+]; Found:553.3532.
All the other glycosyl derivatives can be according to the method described above, change that reaction substrate is synthetic to be obtained.
By test example, beneficial effect of the present invention is described below.
Test example 1 skin care experiment
Group material A: sweet oil 20ml, Creager emulsifying agent 1ml, glycerine 10ml, pure water 70ml; Group material B: compound 2 (lactose saponin(e RT-1) 3% or compound 3(ribose saponin(e HT-1) 3%, after stirring after group material A is compound, 40 ℃ add group to expect B, stir and obtain experiment skin care product.
RT-1 and HT-1 are carried out to humidity-holding effect assessment, method be 38-50 year each 20 of the female volunteers of age bracket in every day, sooner or later do not use any other skin care product after clean, the experiment skin care product that add RT-1 or HT-1 are applied to face.Adopt conventional skin care product humidity-holding effect evaluation method, at 1 week, use respectively the rear humidity-holding effect with using postevaluation the compounds of this invention for month.5 are divided into best result, represent that effect is very good; 4 be divided into fine; 3 are divided into successful; 2 be divided into invalid.The results are shown in following table.
| Assessment item | Average |
| RT-1 is used 1 week humidity-holding effect | 4.1 |
| HT-1 is used 1 week humidity-holding effect | 3.8 |
| RT-1 is used 1 month humidity-holding effect | 4.5 |
| HT-1 is used 1 month humidity-holding effect | 4.0 |
| RT-1 is used 1 month whole improvement of skin | 4.5 |
| HT-1 is used 1 month whole improvement of skin | 4.1 |
Visible, RT-1(compound 2) and HT-1(compound 3) all there is good humidity-holding effect, particularly RT-1 effect is more obvious, and its moisturizing activity is better than RT-1.
Test example 2 anti-tumor experiments
Test cell line
Experimental technique:
1) collect logarithmic phase cell, adjust concentration of cell suspension, every hole adds 100ul, and bed board makes cell to be measured adjust density 2000-3000 hole (marginal pore is filled with aseptic PBS).
2) 5%CO
2, hatch for 37 ℃, at the bottom of being paved with hole to cell monolayer (96 hole flat underside), every hole 100ul, establishes 3 multiple holes.After administration, continue to hatch 48 hours, under inverted microscope, observe.
3) every hole adds 20 μ l MTT solution (5mg/ml, i.e. 0.5%MTT), continues to cultivate 4h.
4) stop cultivating, carefully suck nutrient solution in hole.Every hole adds 150ul dimethyl sulfoxide (DMSO), puts low-speed oscillation 10min on shaking table, and crystallisate is fully dissolved.At enzyme-linked immunosorbent assay instrument 570nm place, measure the light absorption value in each hole.
Adopt mammary cancer MDA-MB 231 cell screening dioscin glycosylated derivative anti-tumor activities, the results are shown in Table 1:
Table 1
As seen from the above table, dioscin glycosylated derivative of the present invention has antitumour activity, wherein better with compound 2,3 antitumour activitys, is better than diosgenin.
Dioscin glycosylated derivative of the present invention, not only has good anti-tumor activity, also has skin moisture-keeping activity, for the preparation of cancer therapy drug or functional cosmetics provides new selection.
Claims (10)
1. the dioscin glycosylated derivative shown in formula I:
R is pentose base or lactose base.
2. dioscin glycosylated derivative according to claim 1, is characterized in that: described pentose base is selected from D/L-ribosyl, D/L-aralino, 2-deoxyribosyl base or 5-deoxyribosyl.
3. dioscin glycosylated derivative according to claim 1 and 2, is characterized in that: described dioscin glycosylated derivative is
4. a method of preparing dioscin glycosylated derivative described in claim 1, is characterized in that: it comprises following operation steps:
(1) pentose or lactose, prepare by acylation reaction the carbohydrate intermediate that full acidylate is protected;
(2) get the carbohydrate intermediate that diosgenin, step (1) prepare, directly carry out after glycosylation reaction, under alkaline environment, deprotection base, prepares target compound.
5. preparation method according to claim 4, is characterized in that: in step (1), described pentose is selected from D/L-ribosyl, D/L-aralino, 2-deoxyribosyl, 5-ribodesose.
6. preparation method according to claim 4, is characterized in that: in step (1), adopt acetic anhydride as acetylizing agent, pyridine or sodium acetate are made catalyzer;
In step (2), using tin tetrachloride or trifluoromethanesulfonic acid trimethylsilyl group as catalyzer, carry out glycosylation reaction, alkaline environment is 0.1-0.5mol/L NaOCH
3/ CH
3oH solution room temperature environment.
7. the purposes of the dioscin glycosylated derivative described in claim 1-3 any one in preparing Moisturizer.
8. a Moisturizer, is characterized in that: it is to be activeconstituents by the dioscin glycosylated derivative described in claim 1-3 any one, adds the external preparation that conventional auxiliary material is prepared from.
9. the purposes of the dioscin glycosylated derivative described in claim 1-3 any one in preparing anti-tumor drug.
10. purposes according to claim 9, is characterized in that: described medicine is the medicine for the treatment of mammary cancer.
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| CN105175478A (en) * | 2015-09-16 | 2015-12-23 | 华东师范大学 | Epiandrosterone/dehydrogenated epiandrosterone glycosylation derivatives, and preparation method and application |
| WO2017191893A1 (en) * | 2016-05-03 | 2017-11-09 | 전남대학교산학협력단 | Conjugate of primary amine and diosgenin, preparation method therefor, and anticancer composition comprising same |
| CN110028546A (en) * | 2019-03-30 | 2019-07-19 | 四川大学华西医院 | The pentamethylene and more hydrogen phenanthrene framework compounds and application thereof of antitumor action are played with regulation factor VIII activity level |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105175478A (en) * | 2015-09-16 | 2015-12-23 | 华东师范大学 | Epiandrosterone/dehydrogenated epiandrosterone glycosylation derivatives, and preparation method and application |
| WO2017191893A1 (en) * | 2016-05-03 | 2017-11-09 | 전남대학교산학협력단 | Conjugate of primary amine and diosgenin, preparation method therefor, and anticancer composition comprising same |
| CN110028546A (en) * | 2019-03-30 | 2019-07-19 | 四川大学华西医院 | The pentamethylene and more hydrogen phenanthrene framework compounds and application thereof of antitumor action are played with regulation factor VIII activity level |
| CN110028546B (en) * | 2019-03-30 | 2021-11-16 | 四川大学华西医院 | Cyclopentane-polyhydrophenanthrene framework compound with function of regulating blood coagulation factor VIII level to play anti-tumor role and application thereof |
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