CN104861011A - /-Borneol-alpha-D-glucopyranoside - Google Patents
/-Borneol-alpha-D-glucopyranoside Download PDFInfo
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- CN104861011A CN104861011A CN201410058204.0A CN201410058204A CN104861011A CN 104861011 A CN104861011 A CN 104861011A CN 201410058204 A CN201410058204 A CN 201410058204A CN 104861011 A CN104861011 A CN 104861011A
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- C—CHEMISTRY; METALLURGY
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- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/203—Monocyclic carbocyclic rings other than cyclohexane rings; Bicyclic carbocyclic ring systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
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Abstract
The invention relates to a synthesis method for an important active ingredient /-borneol-alpha-D-glucopyranoside of an herb ophiopogon japonicas, wherein the synthesis method comprises two steps such as an addition reaction and a decarboxylation protection reaction. According to the present invention, borneol and D-glucose are adopted as the starting raw materials and the simple two-step reaction is performed to successfully synthesize the /-borneol-alpha-D-glucopyranoside, and the technical difficulties of raw material refining, low reaction yield, and the like are successfully overcome.
Description
Technical field
The present invention relates to the synthetic method of an important activity composition borneol time glycosides (d-Bomeol glucoside) of medicinal material tuber of dwarf lilyturf.
Background technology
Borneol time glycosides (d-Bomeol glucoside) is main Chinese medicinal materials---the important activity composition of the tuber of dwarf lilyturf in Shenmai injection; there is protection apoptosis of cardiac muscle, promote the effects such as myocardium endotheliocyte NO release and anti-low-density lipoprotein oxydasis; research before inventor also shows the apoptosis of cardiac muscle that borneol time glycosides can obviously suppress ischemia/reperfusion (I/R) to cause; and have concentration dependant effect; the effect having stronger promotion NO to discharge and stronger antioxidant effect are one of Major cardiovascular activeconstituentss in the tuber of dwarf lilyturf.The production place of dwarf lilyturf root selected by Shenmai injection gone on the market at present is different, be mainly the Zhejiang tuber of dwarf lilyturf and river tuber of dwarf lilyturf, through multinomial research, contriver finds that the content of borneol time glycosides in Zhejiang tuber of dwarf lilyturf is much larger than river tuber of dwarf lilyturf, therefore this composition may be used for determining that the medicinal material base of the tuber of dwarf lilyturf is former, thus contribute to the quality good or not evaluating Shenmai injection.
As far back as nineteen eighty-three, (the .Studies on the Components of such as Jin Tianxuan such as Jin Tianxuan
ophiopogonroots (China). I [J] .Yakugaku zasshi.1983,103 (11): 1133-1139.) first from Zhejiang tuber of dwarf lilyturf of 20kg (
ophiopogon japonicusker-Gawler) get borneol time glycosides 300 mg in, utilize MS,
1h-NMR and
13c-NMR, and the method for TLC and GLC standard control after acid hydrolysis, confirm that the absolute chemical structure of borneol time glycosides is:
l-Borneol-α-D-glucopyranoside.
In addition, there is report from composite family feverwort (Motoo Tori. Sesquiterpenoids Isolated from Eupatorium glehnii.Isolation of Guaiaglehnin A, Structure Revision of Hiyodorilactone B and Genetic Comparison [J] .Chem.Pharm.Bull. 2008,56 (5): 677-681.) and Labiatae Thymus plant
thymus vulgarisleaf L. (Junichi Kitajima.Monoterpenoids and their glycosides from the leaf of thyme [J]. Phytochemistry. 2004 (65): 3279 – 3287.) in, also get borneol time glycosides.The plant reported containing borneol time glycosides only has the Zhejiang tuber of dwarf lilyturf (yield 300mg/20kg),
eupatorium glehnii(yield 4.5mg/4.4kg medicinal material) and thyme leaf (yield 120mg/2kg), wherein the content of thyme leaf is the highest, is about 4 times of Zhejiang tuber of dwarf lilyturf.Borneol time glycosides is extracted from plant, even if calculate with the thyme leaf that content is the highest, the borneol time glycosides obtaining 10g also needs the medicinal material of at least 200kg, workload is very large and exceed the equipment requirements in laboratory, and the synthesis of borneol time glycosides does not have reported in literature, therefore be badly in need of fast a kind of, easy at present, the borneol time glycosides synthetic method that yield is higher.
Summary of the invention
Technical problem solved by the invention finds one fast, and easy borneol time glycosides synthesis technique, replaces the method extracted in the natural phant of high production cost.
The present invention intend d-Bomeol (
i) and acetyl bromide-alpha-D-glucose (
iI) carry out borneolum syntheticum time glycosides as raw material, the technical scheme provided comprises following two reactions steps:
1) with protection of inert gas, in anhydrous organic solution, with compound
i((-)-Borneol, CAS:464-45-9) and compound
iI(Acetobromo-α-D-glucose, CAS:572-09-8) is raw material, is that phase-transfer catalyst carries out lucifuge reaction, needs to add siccative in reaction with silver carbonate.Wherein organic solvent is methylene dichloride, toluene, ether, dimethyl sulfoxide (DMSO) or methyl alcohol; The mass ratio of Compound I and Compound II per is 1:0.5 ~ 8; The mass ratio of Compound I and catalyzer silver carbonate is 1:0.5 ~ 6; Siccative is molecular sieve, Calcium Chloride Powder Anhydrous, anhydrous magnesium sulfate or soda-lime; Temperature of reaction is 0 DEG C ~ 60 DEG C; Reaction times is 10 ~ 48h.Concentrated after reacting liquid filtering, obtain reactant crude product, crude product recrystallization after silica gel column chromatography separation and Extraction, obtains intermediate compound III.
2) under protection of inert gas condition, by the product Compound in reactions steps 1
iIIbe dissolved in anhydrous methanol, add 1 M sodium methoxide solution of fresh preparation, room temperature reaction, to completely, is adjusted reacting liquid pH value to neutral stopped reaction, is filtered, concentrated, obtain reactant crude product, crude product reversed-phase silica gel column chromatography method separation and Extraction, concentrated, drying, obtains the compound borneol time glycosides of white powder after recrystallization.
This reactions steps 1) preferably organic solvent be methylene dichloride, the mass ratio of Compound I and Compound II per is 1:2 ~ 4; The mass ratio of Compound I and catalyzer silver carbonate is 1:2 ~ 4; Siccative is molecular sieve; Temperature of reaction is 20 DEG C ~ 40 DEG C; Reaction times is 20 ~ 30h.
accompanying drawing explanation
The operational path of accompanying drawing 1 invention.
embodiment
The present invention is described further by following embodiment, and described embodiment is not understood to further restriction.Ad hoc approach described in those skilled in the art's easy to understand and result are only illustrative.
Embodiment 1
1) synthesis of compound III
Under argon shield condition, by 4.0 grams of (-)-Borneol, 2 grams of acetyl bromide-alpha-D-glucoses, and appropriate Calcium Chloride Powder Anhydrous adds in dry methylene chloride, stirs 5 minutes, then adds 14 grams of silver carbonates, lucifuge stirring reaction 24 hours.Reacting liquid filtering, silica gel column chromatography roughing out after concentrated, obtains compound
iIIcrude product, obtain the compound of white, needle-shaped crystals with sherwood oil recrystallization
iII, yield is 24.0%.
2) synthesis of borneol time glycosides
Under argon shield condition; 3 g of compound III are dissolved in anhydrous methanol; add the 1M sodium methoxide solution of the fresh preparation of 6.2 mL, after thin-layer chromatography monitoring reacts completely, filter; concentrated; reversed phase column chromatography is separated, and by methanol-eluted fractions, obtains white powder compound; structural identification is borneol time glycosides, and yield is 54.0%.
Embodiment 2
The present embodiment method is with embodiment 1, and difference is that the charging capacity of Compound II per in reaction 1 becomes 12.0g, and reacting 1 ultimate yield is 56.2%
Embodiment 3
The present embodiment method is with embodiment 1, and difference is that the charging capacity of Compound II per in reaction 1 becomes 32.0g, and reacting 1 ultimate yield is 52.1%.
Embodiment 4
The present embodiment method is with embodiment 1, and difference is that the charging capacity of catalyzer in reaction 1 becomes 2.0g, and reacting 1 ultimate yield is 12.7%.
Embodiment 5
The present embodiment method is with embodiment 1, and difference is that the charging capacity of catalyzer in reaction 1 becomes 40.0g, and reacting 1 ultimate yield is 44.7%.
Embodiment 6
The present embodiment method is with embodiment 2, and difference is that the water-retaining agent of reaction 1 changes molecular sieve into, and reacting 1 ultimate yield is 63.0%.
Embodiment 7
The present embodiment method is with embodiment 2, and difference is that the water-retaining agent of reaction 1 changes anhydrous magnesium sulfate into, and reacting 1 ultimate yield is 53.3%.
Embodiment 8
The present embodiment method is with embodiment 2, and difference is that the water-retaining agent of reaction 1 changes soda-lime into, and reacting 1 ultimate yield is 40.0%.
Embodiment 9
The present embodiment method is with embodiment 6, and difference is that the organic solvent of reaction 1 changes toluene into, and reacting 1 ultimate yield is 42.8%.
Embodiment 10
The present embodiment method is with embodiment 6, and difference is that the organic solvent of reaction 1 changes ether into, and reacting 1 ultimate yield is 22.5%.
Embodiment 11
The present embodiment method is with embodiment 6, and difference is that the organic solvent of reaction 1 changes methyl-sulphoxide into, and reacting 1 ultimate yield is 52.1%.
Embodiment 12
The present embodiment method is with embodiment 6, and difference is that the organic solvent of reaction 1 changes methyl alcohol into, reaction
1 ultimate yield is 12.4%.
Embodiment 13
The present embodiment method is with embodiment 6, and difference is that the reaction times of reaction 1 is 10 hours, and reacting 1 ultimate yield is 43.2%.
Embodiment 14
The present embodiment method is with embodiment 6, and difference is that the reaction times of reaction 1 is 48 hours, and reacting 1 ultimate yield is 34.0%.
Embodiment 15
The present embodiment method is with embodiment 6, and difference is that the reaction times of reaction 1 is 0 DEG C, and reacting 1 ultimate yield is 37.7%.
Embodiment 16
The present embodiment method is with embodiment 6, and difference is that the reaction times of reaction 1 is 60 DEG C, and reacting 1 ultimate yield is 27.4%.
Claims (10)
1. the synthetic method of borneol time glycosides, comprise the following steps: with d-Bomeol and acetyl bromide-alpha-D-glucose for starting raw material, under protection of inert gas condition, add water-retaining agent, anhydrous organic solvent, be that catalyst reaction is to abundant with silver carbonate, reacting liquid filtering, column chromatography for separation, recrystallization obtains intermediate product; Under inert gas conditions, be dissolved in by intermediate product in anhydrous methanol, with the 1M sodium methoxide solution of fresh preparation for catalyzer, room temperature reaction is to complete, and separating-purifying obtains borneol time glycosides.
2. the synthetic method of intermediate product according to claim 1, is characterized in that the mass ratio of d-Bomeol described in it and acetyl bromide-alpha-D-glucose is 1:0.5 ~ 8.
3. the synthetic method of intermediate product according to claim 2, is characterized in that preferred 1:2 ~ 4 of mass ratio of d-Bomeol described in it and acetyl bromide-alpha-D-glucose.
4. the synthetic method of intermediate product according to claim 1, is characterized in that the mass ratio of d-Bomeol described in it and catalyzer silver carbonate is 1:0.5 ~ 6.
5. the synthetic method of compound III according to claim 4, is characterized in that preferred 1:2 ~ 4 of mass ratio of d-Bomeol described in it and catalyzer silver carbonate.
6. the synthetic method of intermediate product according to claim 1, is characterized in that the water-retaining agent described in it can be molecular sieve, Calcium Chloride Powder Anhydrous, anhydrous magnesium sulfate or soda-lime.
7. the synthetic method of intermediate product according to claim 1, is characterized in that the organic solvent described in it can be methylene dichloride, toluene, ether, dimethyl sulfoxide (DMSO) or methyl alcohol.
8. the synthetic method of intermediate product according to claim 1, is characterized in that temperature of reaction described in it is 0 DEG C ~ 60 DEG C.
9. synthetic method according to claim 1, is characterized in that the rare gas element described in it can be argon gas or nitrogen.
10. the synthetic method of intermediate product according to claim 1, is characterized in that the reaction times described in it is 10-48 hour.
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| CN201410058204.0A CN104861011A (en) | 2014-02-21 | 2014-02-21 | /-Borneol-alpha-D-glucopyranoside |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105388228A (en) * | 2015-12-04 | 2016-03-09 | 正大青春宝药业有限公司 | Method for discriminating different producing areas of dwarf lilyturf tubers |
| CN107595862A (en) * | 2017-10-16 | 2018-01-19 | 正大青春宝药业有限公司 | A kind of borneol time glycosides is preparing the application in treating cardiovascular disease medicine |
| CN107693683A (en) * | 2017-10-16 | 2018-02-16 | 正大青春宝药业有限公司 | A kind of borneol time glycosides Shenmai injection and its application |
| CN110426486A (en) * | 2019-08-01 | 2019-11-08 | 正大青春宝药业有限公司 | The discrimination method of Zhejiang Radix Ophiopogonis in Chinese materia medica preparation |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101735018A (en) * | 2010-01-22 | 2010-06-16 | 嘉兴金满林木有限责任公司 | Method for extracting natural D-bornel from branches and leaves of camphor trees |
-
2014
- 2014-02-21 CN CN201410058204.0A patent/CN104861011A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101735018A (en) * | 2010-01-22 | 2010-06-16 | 嘉兴金满林木有限责任公司 | Method for extracting natural D-bornel from branches and leaves of camphor trees |
Non-Patent Citations (2)
| Title |
|---|
| S. A. PATOV, ET AL.,: "Synthesis of certain monoterpenoid glucosides.", 《CHEMISTRY OF NATURAL COMPOUNDS》 * |
| 程志红等，: "中药麦冬脂溶性化学成分的研究.", 《中国药学杂志》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105388228A (en) * | 2015-12-04 | 2016-03-09 | 正大青春宝药业有限公司 | Method for discriminating different producing areas of dwarf lilyturf tubers |
| CN107595862A (en) * | 2017-10-16 | 2018-01-19 | 正大青春宝药业有限公司 | A kind of borneol time glycosides is preparing the application in treating cardiovascular disease medicine |
| CN107693683A (en) * | 2017-10-16 | 2018-02-16 | 正大青春宝药业有限公司 | A kind of borneol time glycosides Shenmai injection and its application |
| CN110426486A (en) * | 2019-08-01 | 2019-11-08 | 正大青春宝药业有限公司 | The discrimination method of Zhejiang Radix Ophiopogonis in Chinese materia medica preparation |
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