CN104490894B - The preparation method of Spermacoce latifolia triterpenoid and its preparing the application in glycosidase inhibitor - Google Patents

The preparation method of Spermacoce latifolia triterpenoid and its preparing the application in glycosidase inhibitor Download PDF

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CN104490894B
CN104490894B CN201410718340.8A CN201410718340A CN104490894B CN 104490894 B CN104490894 B CN 104490894B CN 201410718340 A CN201410718340 A CN 201410718340A CN 104490894 B CN104490894 B CN 104490894B
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compound
acid
alpha
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glucosidase
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CN104490894A (en
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谭建文
罗应
周忠玉
任慧
徐巧林
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South China Botanical Garden of CAS
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Abstract

The present invention provides the preparation method of Spermacoce latifolia triterpenoid and its preparing the application in glycosidase inhibitor.Six kinds of tools of the invention are potent inhibit the active compound of alpha-glucosidase be it is highly-safe and in the environment can rapid and natural degrade the native compound of noresidue, they can separate acquisition from the vegetable materials such as Spermacoce latifolia, source of plant material is abundant, and preparation process is easily operated.The monomer of six kinds of compounds is more stable, easy to store, their alpha-glucoside inhibiting activity is significantly stronger than clinical application acarbose, it is most probably further development of the α-glucosidase inhibitors drug of effective, safe prevention and treatment type II diabetes, there is preferable prospect.

Description

The preparation method of Spermacoce latifolia triterpenoid and its preparing glycosidase inhibitor Application in drug
Technical field
The invention belongs to field of natural medicinal chemistry, and in particular to six kinds of triterpene compounds are mesembryanthemoidigenic acid(1)、29-hydroxyhederagenin(2)、3β,6β-dihydroxy- olean-12-ene-28-oic acid(3)、scutellaric acid(4)、arjunic acid(5)、3β,6β,23- Trihydroxy-olean-12-en-28-oic acid (6) or its pharmaceutical salt are in preparing glycosidase inhibitor or drug Application and their preparation method.
Background of invention
Diabetes are clinically common endocrine metabolism dysfunctional disease, high year by year with cardiovascular disease and cancer etc. Hair has important correlation, is the important killer of human health.Currently, the disease incidence of diabetes is mentioning in the world Height is even more the illness rate for having more than 100,000,000 people in China, and increased trend year by year is presented.Diabetes just give the health of our people More and more great loss is caused with national economy.
Diabetes doctor trained in Western medicine is divided into Type I diabetes (or insulin-dependent, DM1) and type II diabetes (or non-pancreas islet Plain dependence, DM2), wherein type II diabetes morbidity is much higher than Type I diabetes with illness rate, thus endangers bigger.It is competitive There is alpha-glucosidase inhibitor postponement glucide to digest and assimilate, blood glucose sharply increases and then blood sugar concentration is made to exist after meal for control Change the functions such as fluctuating range reduction in one day, is the potential drug that can be developed for treating type II diabetes.It has developed at present Listing positive clinic trial to make the important alpha-glucosidase inhibitor for the treatment of type II diabetes includes fiest-tire medication acarbose (A Kabo Sugar), voglibose, miglitol and emigliate etc..
Six kinds of triterpenoid mesembryanthemoidigenic acid (1), 29-hydroxyhederagenin (2)、3β,6β-dihydroxy-olean-12-ene-28-oic acid(3)、scutellaric acid(4)、arjunic Acid (5), 3 β, 6 β, 23-trihydroxy-olean-12-en-28-oic acid (6) were once separated from other plant respectively Acquisition (is specifically shown in document: Magina et al., Quim Nova, 2012,35:1184-1188；Huu et al.,J Chem, 2007,45:363-367；Kuo et al.,Chem Pharm Bull,1988,36:3619-3622；Ponouet al.,Chem Biodivers,2011,8:1301-1309；Lavaud et al.,Phytochemistry,2001,57:469-478；Khan Et al., J Nat Prod, 1993,56:2163-2165), shown in their chemical structural formula such as following formula (I), at present also not Seeing these compounds has the report of glucosidase inhibitor activity, and has no it from Spermacoce latifolia (Spermacoce Latifolia the report of acquisition) is separated in plant.
Summary of the invention
The first purpose of the invention is to provide compound mesembryanthemoidigenic acid (1), 29- hydroxyhedera genin(2)、3β,6β-dihydroxy-olean-12-ene-28-oic acid(3)、 scutellaric acid(4)、arjunic acid(5)、3β,6β,23-trihydroxy-olean-12-en-28-oic Acid (6) or their officinal salt are preparing the application in alpha-glucosidase inhibitor drug.
It is confirmed through external pharmacological evaluation, compound mesembryanthemoidigenic acid (1) provided by the invention, 29-hydroxyhederagenin(2)、3β,6β-dihydroxy-olean-12-ene-28-oic acid(3)、 Scutellaric acid (4), arjunic acid (5) or 3 β, 6 β, 23-trihydroxy-olean-12-en-28-oic Acid (6) all has the potent activity for inhibiting alpha-glucosidase, they inhibit the activity of alpha-glucosidase to be significantly stronger than Diabetes fiest-tire medication acarbose, thus can develop preparation for preventing and treating alpha-glucosidase causes or related physiology changes The potential drug candidate molecules of change or disease.Wherein, cause with alpha-glucosidase or related physiological change or disease include but not It is limited to type II diabetes.
The pharmaceutical salt of six kinds of compounds of the present invention, can under the physiological conditions such as gastric acid in people's alimentary canal Be converted into and correspond to triterpenoid molecule shown in above formula (I), substance inhibit alpha-glucosidase active constituent with Six kinds of triterpenoid molecules illustrated above are identical, thus belong to strict protection range of the invention.
Above-described six kinds of triterpenoid molecules of the invention or its pharmaceutical salt can be with pharmaceutically common auxiliary materials Or carrier combines, any one or more being prepared with six kinds of compound molecules described above inhibits alpha-glucosidase activity The drug or pharmaceutical composition that can be used for preventing and treating type II diabetes.Wettable can be used in the drug or pharmaceutical composition The dosage forms such as pulvis, tablet, granule, capsule, oral solution, dripping pill, also can be used controlled release or sustained-release dosage type well known to pharmaceutical industry or Nanometer formulation.
With one of above six kinds of triterpenoid molecules of the present invention or it is a variety of be effective component include wealthy The extract of the plants such as leaf spermacoce latifolia is preparing the application in alpha-glucosidase inhibitor drug, because it is with of the present invention six One of kind of compound molecule is a variety of for substantive effective component, thus belongs to strict protection range scope of the invention.
A second object of the present invention is to provide compound mesembryanthemoidigenic acid (1), 29- hydroxyhederagenin(2)、3β,6β-dihydroxy-olean-12-ene-28-oic acid(3)、scutellaric Acid (4), arjunic acid (5), 3 β, 6 β, the preparation of 23-trihydroxy-olean-12-en-28-oic acid (6) Method, which is characterized in that compound mesembryanthemoidigenic acid (1), the 29- hydroxyhederagenin(2)、3β,6β-dihydroxy-olean-12-ene-28-oic acid(3)、scutellaric Acid (4), arjunic acid (5), 3 β, 6 β, 23-trihydroxy-olean-12-en-28-oic acid (6) are from wealthy It is isolated in leaf spermacoce latifolia (Spermacoce latifolia Aubl.K.Schum.) plant.
It is preferred that specific steps are as follows:
It is extracted after dry Spermacoce latifolia complete stool is crushed with ethyl alcohol or ethanol water, is obtained after extracting solution is concentrated Medicinal extract, medicinal extract add water to be suspended, and are successively extracted with petroleum ether and ethyl acetate, respectively obtain petroleum ether portion and second after concentration Acetoacetic ester extracts part；Petroleum ether portion is through normal-phase silica gel column chromatography, with petroleum ether/acetone from volume ratio 100:0-0- 100 gradient elutions, collect petroleum ether-acetone volume ratio 10:1 elution fraction E6, and fraction E6 removes depigmentaton through MCI column, uses first Alcohol affords methanol-eluted fractions E6-1, and E6-1 passes sequentially through reverse phase medium pressure column chromatography, and methanol/water volume ratio is from 30:70- 100:0 gradient elution, Sephadex LH-20 gel column, are eluted with methanol and purification on normal-phase silica gel chromatographs, with chloroform/methanol volume It is eluted than 100:1, obtains compound 1；
Ethyl acetate extraction part is washed with chloroform/methanol from volume ratio 100:1-0:100 gradient through normal-phase silica gel column chromatography It is de-, collect the fraction F of chloroform/methanol volume ratio 25:1 elution5, F5Inverted medium pressure column chromatography, methanol/water is from volume ratio 30: 70-100:0, gradient elution collect the fraction F of methanol/water volume ratio 80:20 elution5-4It is eluted with methanol/water volume ratio 90:10 Fraction F5-5；Fraction F5-4It is eluted through Sephadex LH-20 gel column with methanol, then chromatographs column separating purification through purification on normal-phase silica gel, With chloroform/methanol volume ratio 50:1 elution, compound 3,4,5 and 6 is obtained；Fraction F5-5Through Sephadex LH-20 gel column with Methanol elution, obtains compound 2.
Third object of the present invention is to provide Spermacoce latifolias in prepare compound mesembryanthemoidigenic acid(1)、29-hydroxyhederagenin(2)、3β,6β-dihydroxy-olean-12-ene-28-oic acid(3)、 Scutellaric acid (4), arjunic acid (5) or 3 β, 6 β, 23-trihydroxy-olean-12-en-28-oic Application in acid (6).
Six kinds of tool active compounds of potent inhibition alpha-glucosidase of the invention are highly-safe and in the environment can be quick The native compound of natural degradation noresidue, they can separate acquisition from the vegetable materials such as Spermacoce latifolia, and vegetable material comes Source is abundant, and preparation process is easily operated.The monomer of six kinds of compounds is more stable, easy to store, their alpha-glucosidase Inhibitory activity is significantly stronger than or is equivalent to clinical application acarbose, be most probably further development of effective, safe prevention and The α-glucosidase inhibitors drug of type II diabetes is treated, there is preferable prospect.
Detailed description of the invention:
Fig. 1 is compound mesembryanthemoidigenic acid (1)13C NMR spectra.
Fig. 2 is (2) compound 29-hydroxyhederagenin13C NMR spectra.
Fig. 3 is 3 β of compound, 6 β-dihydroxy-olean-12-ene-28-oic acid's (3)13C NMR spectra.
Fig. 4 is compound scutellaric acid (4)13C NMR spectra.
Fig. 5 is compound a rjunic acid (5)1H NMR spectra.
Fig. 6 is 3 β of compound, 6 β, 23-trihydroxy-olean-12-en-28-oic acid's (6)13C NMR figure Spectrum.
Specific embodiment:
The following examples are further illustrations of the invention, rather than limiting the invention, reality according to the present invention The simple modifications that the present invention carries out of verifying belong to the scope of protection of present invention.
Embodiment 1: the preparation of six kinds of triterpenoids in Spermacoce latifolia plant
1.1 plant origins and identification
Spermacoce latifolia (Spermacoce latifolia Aubl.K.Schum.) plant complete stool was adopted in 09 month 2012 From Guangzhou, Guangdong South China Botanical Garden, identified through South China Botanical Garden Chinese Academy of Sciences Xing Fuwu researcher.
1.2 extract and separate
Dry Spermacoce latifolia complete stool (5.0Kg) is mentioned in room temperature with the ethanol water of volume fraction 95% after crushing It takes, extracting solution is concentrated under reduced pressure without alcohol medicinal extract after merging.Medicinal extract adds water to be suspended, successively with petroleum ether and ethyl acetate extraction each 4 It is secondary；Petroleum ether portion (330g) and ethyl acetate extraction part (202g) are obtained after reduced pressure.Obtained petroleum ether extraction Partially (330g) through normal-phase silica gel column chromatography (200-300 mesh, 1000 × 105mm i.d.), with petroleum ether-acetone (100:0-0: 100, v/v, each 3.0L) through the identical flow point of TLC thin-layer chromatography combining data detection principal point 9 components are obtained in gradient elution (E1-E9)。E6(5.0g) [fraction of petroleum ether-acetone (10:1, v/v) elution] removes discoloration through MCI column [200 × 40mm i.d.] Element affords methanol-eluted fractions E with methanol6-1。E6-1(3.0g) passes sequentially through reverse phase medium pressure column chromatography and isolates and purifies, first Alcohol/water (30:70-100:0, v/v, each 1.0L) be eluent gradient elution, Sephadex LH-20 gel column (1550 × 13.4mm i.d.) it is isolated and purified with methanol elution and purification on normal-phase silica gel chromatographic column (200-300 mesh, 400 × 30mm i.d), with chlorine The elution of imitation-carbinol (100:1, v/v) constant gradient, obtains compound 1 (3.4mg).Ethyl acetate extraction part (202g) is through just Phase silica gel column chromatography (200-300 mesh, 1000 × 105mm i.d.), with chloroform-methanol (100:1-0:100, v/v, each 3.0L) gradient elution obtains F through the identical flow point of TLC thin-layer chromatography combining data detection principal point1-F9Totally 9 components.F5(3.3g) [fraction of chloroform-methanol (25:1, v/v) elution] continues inverted medium pressure column chromatography and isolates and purifies, methanol/water (30:70- 100:0, v/v, each 1.0L) it is that eluent gradient elutes, the identical flow point of TLC thin layer combining data detection principal point obtains 6 Asias Component (F5-1-F5-6)。F5-4(2.5g) fraction of elution [methanol/water (80:20, v/v)] through Sephadex LH-20 gel column with Methanol elution, then isolates and purifies through purification on normal-phase silica gel chromatographic column (200-300 mesh, 400 × 30mm i.d.), with chloroform-methanol (50: 1, v/v) constant gradient elutes, and obtains compound 3 (5.6mg), 4 (3.6mg), 5 (5.0mg) and 6 (4.0mg).F5-5(1.0g) [fraction of methanol/water (90:10, v/v) elution] is eluted through Sephadex LH-20 gel column with methanol, obtains compound 2 (4.2mg)。
The Structural Identification of 1.3 compounds
Obtained compound 1 is white powder, ESI-MS m/z 495 [M+Na]+,471[M-H]–Point of the corresponding compound Minor C30H48O4；Its13C NMR spectra as shown in Figure 1,1H-NMR(500MHz,CD3OD): δ 5.25 (1H, t, J=3.5Hz, H- 12), 3.19 (2H, s, H-29), 3.15 (1H, dd, J=11.4,4.7Hz, H-3), 2.88 (1H, dd, J=13.0,4.7Hz, H- 18),1.17(3H,s),0.97(3H,s),0.94(3H,s),0.93(3H,s),0.82(3H,s),0.78(3H,s)；13C-NMR (125MHz,CD3OD):δ38.5(CH2,C-1),27.6(CH2,C-2),79.7(CH,C-3),38.9(C,C-4),56.7(CH, C-5),18.3(CH2,C-6),32.9(CH2,C-7),39.8(C,C-8),46.5(CH,C-9),36.8(C,C-10),23.2 (CH2,C-11),123.7(CH,C-12),145.2(C,C-13),42.7(C,C-14),28.7(CH2,C-15),24.0(CH2, C-16),47.6(C,C-17),40.6(CH,C-18),40.3(CH2,C-19),35.5(C,C-20),29.6(CH2,C-21), 38.0(CH2,C-22),28.3(CH3,C-23),16.3(CH3,C-24),15.9(CH3,C-25),17.7(CH3,C-26),25.4 (CH3,C-27),181.9(C,C-28),74.4(CH2,C-29),19.5(CH3,C-30).According to comprehensive point of the above spectral data Analysis parses the chemical structure of the compound 1 for mesembryanthemoidigenic acid, in structural formula such as formula (I) 1 shown in.
Obtained compound 2 is white powder, ESI-MS m/z 511 [M+Na]+,487[M-H]–, the corresponding compound molecule Formula C30H48O5；Its13C NMR spectra as shown in Fig. 2,1H-NMR(500MHz,CD3OD): δ 5.26 (1H, t, J=3.5Hz, H- 12), 3.60 (1H, dd, J=11.9,4.2Hz, H-3), 3.53,3.33, (each 1H, d, J=11.0Hz, H-23), 3.19 (2H, s, H-29), 2.88 (1H, dd, J=13.9,4.3Hz, H-18), 1.19 (3H, s), 0.98 (3H, s), 0.93 (3H, s), 0.82(3H,s),0.70(3H,s)；13C-NMR(125MHz,CD3OD):δ38.2(CH2,C-1),26.1(CH2,C-2),75.3 (CH,C-3),40.6(C,C-4),49.5(CH,C-5),18.7(CH2,C-6),32.6(CH2,C-7),39.7(C,C-8),47.4 (CH,C-9),36.7(C,C-10),22.8(CH2,C-11),122.8(CH,C-12),144.5(C,C-13),41.4(C,C- 14),27.7(CH2,C-15),23.2(CH2,C-16),47.7(C,C-17),40.7(CH,C-18),40.7(CH2,C-19), 35.6(C,C-20),28.8(CH2,C-21),32.1(CH2,C-22),68.3(CH2,C-23),11.6(CH3,C-24),15.3 (CH3,C-25),16.8(CH3,C-26),25.4(CH3,C-27),182.7(C,C-28),73.4(CH2,C-29),18.8(CH3, C-30).According to the above spectral data comprehensive analysis, the chemical structure for parsing the compound 2 is 29- Hydroxyhederagenin, structural formula is as shown in 2 in formula (I).
Obtained compound 3 is white powder, ESI-MS m/z 495 [M+Na]+,471[M-H]–, the corresponding compound molecule Formula C30H48O4；Its13C NMR spectra as shown in figure 3,1H-NMR(500MHz,CD3OD): δ 5.30 (1H, t, J=3.6Hz, H- 12), 4.51 (1H, br s, H-6), 3.10 (1H, dd, J=11.6,4.1Hz, H-3), 2.89 (1H, dd, J=13.7,4.2Hz, H-18),1.32(3H,s),1.18(3H,s),1.15(3H,s),1.11(3H,s),1.06(3H,s),0.96(3H,s),0.93 (3H,s)；13C-NMR(125MHz,CD3OD):δ42.0(CH2,C-1),28.1(CH2,C-2),80.1(CH,C-3),40.1(C, C-4),57.1(CH,C-5),68.7(CH,C-6),41.6(CH2,C-7),40.7(C,C-8),49.4(CH,C-9),37.7(C, C-10),24.5(CH2,C-11),123.9(CH,C-12),144.5(C,C-13),43.4(C,C-14),28.7(CH2,C-15), 24.0(CH2,C-16),47.7(C,C-17),40.6(CH,C-18),47.3(CH2,C-19),30.5(C,C-20),33.6 (CH2,C-21),32.0(CH2,C-22),28.3(CH3,C-23),17.6(CH3,C-24),17.3(CH3,C-25),18.8 (CH3,C-26),26.4(CH3,C-27),181.9(C,C-28),23.9(CH3,C-29),31.8(CH3,C-30).According to above Spectral data comprehensive analysis, the chemical structure for parsing the compound 3 is 3 β, 6 β-dihydroxy-olean-12-ene-28- Oic acid, structural formula is as shown in 3 in formula (I).
Obtained compound 4 is white powder, ESI-MS m/z 495 [M+Na]+,471[M-H]–, the corresponding compound molecule Formula C30H48O4；Its13C NMR spectra as shown in figure 4,1H-NMR(500MHz,CD3OD): δ 5.26 (1H, t, J=3.6Hz, H- 12), 3.63 (1H, m, H-3), 3.70,3.44, (each 1H, d, J=11.0Hz, H-23), 2.87 (1H, dd, J=13.8, 4.2Hz,H-18),1.15(3H,s),1.10(3H,s),1.06(3H,s),0.93(3H,s),0.87(3H,s),0.72(3H, s)；13C-NMR(125MHz,CD3OD):δ33.2(CH2,C-1),26.1(CH2,C-2),73.9(CH,C-3),40.6(C,C-4), 43.5(CH,C-5),18.7(CH2,C-6),33.6(CH2,C-7),39.7(C,C-8),49.4(CH,C-9),37.7(C,C- 10),23.5(CH2,C-11),122.8(CH,C-12),144.5(C,C-13),42.4(C,C-14),28.7(CH2,C-15), 24.0(CH2,C-16),47.7(C,C-17),42.1(CH,C-18),46.3(CH2,C-19),31.5(C,C-20),34.2 (CH2,C-21),33.1(CH2,C-22),68.3(CH2,C-23),18.6(CH3,C-24),15.3(CH3,C-25),17.8 (CH3,C-26),26.4(CH3,C-27),181.7(C,C-28),23.9(CH3,C-29),33.8(CH3,C-30).According to above Spectral data comprehensive analysis, the chemical structure for parsing the compound 4 is scutellaric acid, structural formula such as formula (I) In 4 shown in.
Obtained compound 5 is white powder, ESI-MS m/z 511 [M+Na]+,487[M-H]–, the corresponding compound molecule Formula C30H48O5；Its1H NMR spectra as shown in figure 5,1H-NMR(500MHz,CD3OD): δ 5.31 (1H, t, J=3.6Hz, H-12), (3.62 1H, m, H-2), 3.24 (1H, d, J=3.7Hz, H-19), 3.05 (1H, d, J=3.7Hz, H-18), 2.90 (1H, d, J =9.6Hz, H-3), 1.31 (3H, s), 1.03 (3H, s), 1.00 (3H, s), 0.96 (3H, s), 0.93 (3H, s), 0.84 (3H, s),0.76(3H,s)；13C-NMR(125MHz,CD3OD):δ48.2(CH2,C-1),69.6(CH,C-2),84.9(CH,C-3), 40.6(C,C-4),57.0(CH,C-5),19.7(CH2,C-6),34.0(CH2,C-7),40.9(C,C-8),49.4(CH,C-9), 39.7(C,C-10),25.1(CH2,C-11),124.8(CH,C-12),144.9(C,C-13),42.7(C,C-14),29.7 (CH2,C-15),28.6(CH2,C-16),46.7(C,C-17),45.1(CH,C-18),82.3(CH,C-19),36.2(C,C- 20),29.5(CH2,C-21),34.1(CH2,C-22),29.3(CH3,C-23),17.5(CH3,C-24),17.1(CH3,C-25), 17.8(CH3,C-26),25.4(CH3,C-27),181.7(C,C-28),25.2(CH3,C-29),28.8(CH3,C-30).According to The above spectral data comprehensive analysis, the chemical structure for parsing the compound 5 is arjunic acid, structural formula such as formula (I) In 5 shown in.
Obtained compound 6 is white powder, ESI-MS m/z 511 [M+Na]+,487[M-H]–, the corresponding compound molecule Formula C30H48O5；Its13C NMR spectra as shown in fig. 6,1H-NMR(500MHz,CD3OD): δ 5.29 (1H, t, J=3.6Hz, H- 12), 4.39 (1H, br s, H-6), 3.56 (1H, m, H-3), 3.60,3.47, (each 1H, d, J=11.0Hz, H-23), 2.87 (1H, dd, J=13.7,3.9Hz, H-18), 1.33 (3H, s), 1.14 (3H, s), 1.10 (3H, s), 1.06 (3H, s), 0.96(3H,s),0.91(3H,s)；13C-NMR(125MHz,CD3OD):δ41.2(CH2,C-1),28.1(CH2,C-2),73.5 (CH,C-3),44.0(C,C-4),49.5(CH,C-5),68.6(CH,C-6),41.0(CH2,C-7),39.3(C,C-8),48.7 (CH,C-9),36.9(C,C-10),23.7(CH2,C-11),122.8(CH,C-12),144.5(C,C-13),42.4(C,C- 14),28.7(CH2,C-15),24.0(CH2,C-16),46.7(C,C-17),42.1(CH,C-18),46.3(CH2,C-19), 31.0(C,C-20),34.2(CH2,C-21),33.1(CH2,C-22),66.7(CH2,C-23),14.6(CH3,C-24),17.5 (CH3,C-25),18.8(CH3,C-26),26.4(CH3,C-27),181.9(C,C-28),23.7(CH3,C-29),33.2(CH3, C-30).According to the above spectral data comprehensive analysis, the chemical structure for parsing the compound 6 is 3 β, 6 β, 23- Trihydroxy-olean-12-en-28-oic acid, structural formula is as shown in 6 in formula (I).
Embodiment 2: the alpha-glucoside inhibiting activity detection of six kinds of triterpenoids
2.1 instruments and reagent
Laboratory apparatus: microplate reader Genois microplate reader (Tecan GENios, Swizerland).
Reagent sample: alpha-glucosidase purchased from Sigma Chemical Co. (Sigma-Aldrich, St.Louis, USA)；Acarbose (Acarbose) is purchased from Tokyo Chemical Industry Co., Ltd. (Japan)；4- nitrophenols- Alpha-D-glucose pyrans glycosides (PNPG) is purchased from Tokyo Chemical Industry Co., Ltd. (Japan)；Six kinds of triterpenes Object mesembryanth emoidigenic acid (compound 1), 29-hydroxyhederagenin (compound 2), 3 β are closed, 6 β-dihydroxy-olean-12-en e-28-oic acid (compound 3), scutellaric acid (compound 4), Arjunic acid (compound 5), 3 β, 6 β, 23-tr ihydroxy-olean-12-en-28-oic acid (compound 6) by It is prepared by the method for the above experimental example 1, can also according to document Ma gina et al., Quim Nova, 2012,35:1184- 1188；Huu et al.,J Chem,2007,45:363-367；Ku o et al.,Chem Pharm Bull,1988,36: 3619-3622；Ponouet al.,Chem Biodivers,2011,8:1301-1309；Lavaud et al., Phytochemistry,2001,57:469-478；Side in Khan et al., J Nat Prod, 1993,56:2163-2165 Method is prepared.
2.2 test methods:
A) untested compound and acarbose compounding pharmaceutical solution: are prepared into 10mg/ by dimethyl sulfoxide (DMSO) respectively The solution of ml, and the phosphate buffer (ultrapure water preparation) of 67mmol/L is prepared, PNPG substrate solution (match by 5mM, phosphate buffer System) and 0.2M NaCO3Solution (phosphate buffer preparation).
B) colorimetric method is used, half-inhibitory concentration of the untested compound to alpha-glucosidase is surveyed by 96 orifice plates It is fixed.Sample well is added in the alpha-glucosidase (0.8U) of 20 μ l first, then by sample solution with phosphate buffer in proportion 120 μ l of sample solution is added in dilution, every hole, makes the ultimate density of test sample (comprising untested compound and acarbose) are as follows: 500 μ g/mL, 250 μ g/mL, 125 μ g/mL, 62.5 μ g/mL, 31.25 μ g/mL, 15.625 μ g/mL finally add reaction bottom 20 μ l (5mM) of object 4- nitrophenols-α-D- glucopyranoside.After 37 DEG C of water-bath 15min, 80 μ l are added in each sample well Na2CO3(0.2M) terminates reaction, the colorimetric estimation at 405nm wavelength.The phosphate buffer of same volume replaces enzyme solutions.Change It closes object inhibiting rate and blank and control OD value is calculated by sample OD value, calculation formula is as follows: inhibiting rate (%)=(ODcontrol– ODneg)-(ODtest–ODtest control)/(ODcontrol–ODneg) × 100%.Six kinds of compounds are wherein tested respectively to α-Portugal Half-inhibitory concentration (the IC of polyglycoside enzyme50) obtained by dose-effect curve.
2.3 experimental datas are referring to table 1:
The a- glucosidase inhibitory active of 1. 6 kinds of triterpenoids of table
2.4 experiment conclusions:
A- glucuroide is the index tested enzyme of a- glycosidase inhibitor class type II diabetes therapeutic agent screening.This The experimental results showed that compound mesembryanthemoidigenic acid (compound 1) provided by the invention, 29- Hydroxyhederagenin (compound 2), 3 β, 6 β-dihydroxy-olean-12-ene-28-oic acid (compounds 3), scutellaric acid (compound 4), arjunic acid (compound 5) and 3 β, 6 β, 23-trihydroxy- Olean-12-en-28-oic acid (compound 6), which all has, is significantly stronger than diabetes fiest-tire medication acarbose inhibition α-Portugal The activity of polyglycoside enzyme, therefore preparation can be developed and caused for preventing and treating alpha-glucosidase or related physiological change or disease Potential drug candidate molecules, have stronger application and development potential quality, it is expected to can be further developed into as new prevention and treatment The medication of type II diabetes is extensive using potential quality.

Claims (2)

1. compound mesembryanthemoidigenic acid or its officinal salt prevent and treat II type glycosuria in preparation Application in the drug of disease, the compound mesembryanthemoidigenic acid are as shown in Equation 1:
2. application according to claim 1, it is characterised in that: the drug for preventing and treating type II diabetes, agent Type is wettable powder, tablet, granule, capsule, oral solution, dripping pill, controlled release or sustained-release dosage type or nanometer formulation.
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