WO2023070480A1 - Halimane diterpenoid in leucas zeylanica, and preparation method and application thereof - Google Patents

Halimane diterpenoid in leucas zeylanica, and preparation method and application thereof Download PDF

Info

Publication number
WO2023070480A1
WO2023070480A1 PCT/CN2021/127232 CN2021127232W WO2023070480A1 WO 2023070480 A1 WO2023070480 A1 WO 2023070480A1 CN 2021127232 W CN2021127232 W CN 2021127232W WO 2023070480 A1 WO2023070480 A1 WO 2023070480A1
Authority
WO
WIPO (PCT)
Prior art keywords
halimane
preparation
ethyl acetate
honeycomb
extract
Prior art date
Application number
PCT/CN2021/127232
Other languages
French (fr)
Chinese (zh)
Inventor
李小宝
赵婷
陈光英
况家才
农旭华
Original Assignee
海南师范大学
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 海南师范大学 filed Critical 海南师范大学
Priority to PCT/CN2021/127232 priority Critical patent/WO2023070480A1/en
Publication of WO2023070480A1 publication Critical patent/WO2023070480A1/en

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C13/00—Cyclic hydrocarbons containing rings other than, or in addition to, six-membered aromatic rings
    • C07C13/28—Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof
    • C07C13/32—Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof with condensed rings
    • C07C13/38—Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof with condensed rings with a bicyclo ring system containing six carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C13/00—Cyclic hydrocarbons containing rings other than, or in addition to, six-membered aromatic rings
    • C07C13/28—Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof
    • C07C13/32—Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof with condensed rings
    • C07C13/54—Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof with condensed rings with three condensed rings
    • C07C13/605—Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof with condensed rings with three condensed rings with a bridged ring system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C7/00—Purification; Separation; Use of additives
    • C07C7/10—Purification; Separation; Use of additives by extraction, i.e. purification or separation of liquid hydrocarbons with the aid of liquids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C7/00—Purification; Separation; Use of additives
    • C07C7/135—Purification; Separation; Use of additives by gas-chromatography

Definitions

  • the invention relates to the technical field of phytochemistry, in particular to a Halimane type diterpene compound in honeycomb grass and its preparation method and application.
  • Diabetes as one of the major diseases facing the world, is a huge hazard to human health, and the number of people suffering from diabetes has been increasing in recent years.
  • the main cause of diabetes is the occurrence of postprandial hyperglycemia
  • the cause of postprandial hyperglycemia is that ⁇ -glucosidase in the human body hydrolyzes polysaccharides, releasing glucose to increase the blood sugar concentration in the human body. Therefore, one of the effective methods for alleviating and treating diabetic patients is to find substances that can inhibit the activity of ⁇ -glucosidase, so as to achieve the purpose of controlling the enzyme activity.
  • the inhibitors currently used in clinical medical treatment include acarbose, voglibose, etc.
  • ⁇ -glucosidase inhibitors are one of the first-line drugs for the clinical treatment of type 2 diabetes. Their main pharmacological mechanism is to inhibit the transformation of carbohydrates by ⁇ -glucosidase on the brush border of the small intestine, thereby reducing postprandial blood sugar. At present, there are many kinds of hypoglycemic drugs used clinically, and most of them are western medicines. Long-term use will inevitably cause many adverse reactions.
  • honeycomb grass (Leucaszeylanica) is a plant of the genus Lamiaceae. It has the effects of dispelling wind and cold, resolving phlegm and relieving cough.
  • the plant contains many types of compounds such as flavonoids and terpenoids, but there are relatively few research reports on its chemical constituents. Therefore, there is still room for exploration of the chemical constituents of this li medicine. It is particularly important to further discuss its source of life. This project intends to further increase the research on the chemical components of Hainan Li medicine on the basis of the previous work.
  • the object of the present invention is to provide the Halimane type diterpene compound in honeycomb and its preparation method and application, so as to solve the problems raised in the above-mentioned background technology.
  • Halimane type diterpene compound in honeycomb grass its structural formula is as follows:
  • the present invention also provides the preparation method of Halimane type diterpene compound in honeycomb grass, comprising the following steps:
  • Step 1 Air-dry and crush the whole honeycomb grass, soak it in ethanol to get a viscous brown extract
  • Step 2 Disperse the extract in distilled water to obtain a suspension solution, extract the suspension solution 3 times with petroleum ether, combine the extracts to obtain the petroleum ether part; continue to extract 3 times with ethyl acetate, combine the extracts, and depressurize Concentrate to obtain the ethyl acetate part and the aqueous phase part;
  • Step 3 prepare the petroleum ether part through column chromatography, thin layer chromatography, molecular sieve chromatography, and liquid phase to obtain the product.
  • the first step 75% ethanol by volume is used for soaking.
  • condition of the column chromatography in the step three is: forward silica gel column chromatography (CC), using petroleum ether-ethyl acetate as the eluent.
  • the thin-layer chromatography conditions in the step three are as follows: a mixed solvent of petroleum ether-ethyl acetate with a volume percentage of ethyl acetate of 5%-40% is used as a developing solvent.
  • the molecular sieve chromatography conditions in the third step are: the molecular sieve is Sephadex LH-20, and a chloroform-methanol mixed solvent with a volume percentage of chloroform of 0%-50% is used as the eluent.
  • the liquid phase preparation conditions are: Agilent DAD detector 1260LC series C-18 column for separation and purification, chromatographic column specifications: length 250mm, inner diameter 9.4mm, silica gel particle size 5 ⁇ m, mobile phase: methanol-water mixture with a methanol volume fraction of 68% The solution is the eluent.
  • the invention also proposes the application of the Halimane-type diterpene compound in the honeycomb grass in the preparation of hypoglycemic drugs.
  • the invention also proposes a hypoglycemic drug, which contains the Halimane type diterpene compound in the honeycomb grass.
  • the present invention provides a Halimane-type diterpene compound in honeycomb, which has hypoglycemic activity and can be applied to the preparation of hypoglycemic drugs.
  • the preparation process is simple, the cost is low, and the source of raw materials is extensive.
  • Fig. 1 is a schematic diagram of 1 H- 1 H COZY related signals of compound 1 of the present invention.
  • Fig. 2 is a schematic diagram of key HMBC-related signals of Compound 1 of the present invention.
  • Fig. 3 is the 1 H NMR spectrum (methanol-d 4 , 400 MHz) of Compound 1 of the present invention.
  • Fig. 4 is the 13 C NMR spectrum (methanol-d 4 , 100 MHz) of Compound 1 of the present invention.
  • Fig. 6 is the DEPT spectrum of compound 1 of the present invention.
  • Fig. 5 is the HSQC spectrogram of compound 1 of the present invention.
  • Fig. 7 is the COZY spectrum of compound 1 of the present invention.
  • Fig. 8 is the HMBC spectrum of compound 1 of the present invention.
  • the preparation method of Halimane type diterpene compound in honeycomb grass comprises the following steps:
  • Step 1 air-dry and crush the whole honeycomb grass, soak it with 75% ethanol to obtain viscous brown extract;
  • Step 3 Prepare the petroleum ether part through column chromatography, thin layer chromatography, molecular sieve chromatography, and liquid phase to obtain a Halimane type diterpene compound, wherein,
  • the thin-layer chromatography conditions are as follows: a mixed solvent of petroleum ether-ethyl acetate with a volume percentage of 5% ethyl acetate is used as a developing solvent;
  • the molecular sieve chromatography conditions are: the molecular sieve is Sephadex LH-20, and the chloroform-methanol mixed solvent with chloroform volume percentage of 10% is the eluent;
  • the liquid phase preparation conditions are: Agilent DAD detector 1260 LC series C-18 column for separation and purification, chromatographic column specifications: length 250mm, inner diameter 9.4mm, silica gel particle size 5 ⁇ m, mobile phase: methanol-water with a methanol volume fraction of 68%
  • the mixed solution is the eluent.
  • the preparation method of Halimane type diterpene compound in honeycomb grass comprises the following steps:
  • Step 1 air-dry and crush the whole honeycomb grass, soak it with 75% ethanol to obtain viscous brown extract;
  • Step 3 Prepare the petroleum ether part through column chromatography, thin layer chromatography, molecular sieve chromatography, and liquid phase to obtain a Halimane type diterpene compound, wherein,
  • the conditions of column chromatography are: forward silica gel column chromatography, using petroleum ether-ethyl acetate as eluent;
  • the thin-layer chromatography conditions are as follows: a mixed solvent of petroleum ether-ethyl acetate with a volume percentage of 20% ethyl acetate is used as a developing solvent;
  • the molecular sieve chromatography conditions are: the molecular sieve is Sephadex LH-20, and the chloroform-methanol mixed solvent with a chloroform volume percentage of 35% is the eluent;
  • the liquid phase preparation conditions are: Agilent DAD detector 1260 LC series C-18 column for separation and purification, chromatographic column specifications: length 250mm, inner diameter 9.4mm, silica gel particle size 5 ⁇ m, mobile phase: methanol-water with a methanol volume fraction of 68%
  • the mixed solution is the eluent.
  • the preparation method of Halimane type diterpene compound in honeycomb grass comprises the following steps:
  • Step 1 air-dry and crush the whole honeycomb grass, soak it with 75% ethanol to obtain viscous brown extract;
  • Step 3 Prepare the petroleum ether part through column chromatography, thin layer chromatography, molecular sieve chromatography, and liquid phase to obtain a Halimane type diterpene compound, wherein,
  • the conditions of column chromatography are: forward silica gel column chromatography, using petroleum ether-ethyl acetate as eluent;
  • the thin-layer chromatography conditions are as follows: a mixed solvent of petroleum ether-ethyl acetate with a volume percentage of 40% ethyl acetate is used as a developing solvent;
  • the molecular sieve chromatography conditions are: the molecular sieve is Sephadex LH-20, and the chloroform-methanol mixed solvent with a chloroform volume percentage of 50% is the eluent;
  • the liquid phase preparation conditions are: Agilent DAD detector 1260 LC series C-18 column for separation and purification, chromatographic column specifications: length 250mm, inner diameter 9.4mm, silica gel particle size 5 ⁇ m, mobile phase: methanol-water with a methanol volume fraction of 68%
  • the mixed solution is the eluent.
  • compound 1 is a new compound.
  • Step 1 prepare PNPG substrate solution (4-nitrophenyl- ⁇ -D-glucopyranoside) 2.5mM, ⁇ -glucosidase solution 1U, acarbose solution 1mg/mL and PBS buffer pH6 respectively .8;
  • Step 2 Take the prepared PBS buffer solution, the sample to be tested (compounds obtained in Examples 1 to 3), ⁇ -glucosidase solution and PNPG substrate solution and mix well, and react in a water bath at 37°C for 15 minutes.
  • the blank control is no compound added;
  • Step 3 Then add 150 ⁇ L NaCO 3 solution to terminate the reaction;
  • Step 4 Measure the absorbance (A) value at a wavelength of 405nm, that is, the amount of nitrophenol released from the substrate under the action of the enzyme;
  • each sample has ⁇ -glucosidase activity inhibitory effect
  • the Halimane type diterpene compound in the honeycomb grass that the present invention proposes has hypoglycemic activity
  • the present invention proposes that the Halimane type diterpene compound in the honeycomb grass is useful in preparing hypoglycemic drugs and a hypoglycemic drug containing the Halimane type diterpene compound in honeycomb.
  • the preparation process of the Halimane type diterpene compound in honeycomb grass provided by the invention is simple, low in cost, wide in source of raw materials, and has good popularization significance.

Abstract

Disclosed is a halimane diterpenoid in Leucas zeylanica, having a structure as described below, a method for preparing the halimane diterpenoid from Leucas zeylanica, and a use of the halimane diterpenoid in Leucas zeylanica in the preparation of a hypoglycemic drug. The halimane diterpenoid in Leucas zeylanica provided in the present invention has a simple preparation process, low costs and wide raw material sources, has a safe and effective effect in terms of blood sugar reduction, and can be well applied in the preparation of a hypoglycemic drug.

Description

蜂窝草中Halimane型二萜化合物及其制备方法与应用Halimane type diterpene compound in honeycomb and its preparation method and application 技术领域technical field
本发明涉及植物化学技术领域，特别涉及蜂窝草中Halimane型二萜化合物及其制备方法与应用。The invention relates to the technical field of phytochemistry, in particular to a Halimane type diterpene compound in honeycomb grass and its preparation method and application.
背景技术Background technique
糖尿病作为全球面临的主要疾病之一，对人类身体健康的危害巨大，且近些年来患糖尿病的人数不断的增加。患糖尿病的主要原因是餐后高血糖的发生，而导致餐后高血糖发生的原因是人体内的α-glucosidase水解多糖，释放出葡萄糖致使人体血糖浓度的升高。因此缓解及治疗糖尿病患者的有效方法之一是寻找出能对α-glucosidase活性有抑制作用的物质，以达到对酶活性进行控制的目的。目前用于临床医学治疗的抑制剂有阿卡波糖、伏格列波糖等，这些人工合成的抑制剂长期服用对人体有毒副作用，常见的副作用有消化***紊乱等。因此，如果能寻找出一种安全、高效、毒性小的抑制剂对医学治疗糖尿病方面的发展是非常重要的。α-glucosidase抑制剂是临床治疗2型糖尿病的一线药物之一，其主要药理机制是抑制小肠刷状缘上的α-glucosidase对于碳水化合物的转化，从而降低餐后血糖。目前，临床上使用的降糖药物种类繁多，且大多为西药，长期服用难免产生很多不良反应。因此，从中药里开发一种安全有效、价格低廉的降糖中药得到了广大学者的关注。近年来，从植物中提取能够抑制α-glucosidase的物质，并进行分离纯化、结构及相关抑制作用机理的研究，是α-glucosidase抑制剂的研究热点。Diabetes, as one of the major diseases facing the world, is a huge hazard to human health, and the number of people suffering from diabetes has been increasing in recent years. The main cause of diabetes is the occurrence of postprandial hyperglycemia, and the cause of postprandial hyperglycemia is that α-glucosidase in the human body hydrolyzes polysaccharides, releasing glucose to increase the blood sugar concentration in the human body. Therefore, one of the effective methods for alleviating and treating diabetic patients is to find substances that can inhibit the activity of α-glucosidase, so as to achieve the purpose of controlling the enzyme activity. The inhibitors currently used in clinical medical treatment include acarbose, voglibose, etc. Long-term use of these synthetic inhibitors has toxic side effects on the human body, and common side effects include digestive system disorders. Therefore, it is very important for the development of medical treatment of diabetes to find out a safe, efficient and less toxic inhibitor. α-glucosidase inhibitors are one of the first-line drugs for the clinical treatment of type 2 diabetes. Their main pharmacological mechanism is to inhibit the transformation of carbohydrates by α-glucosidase on the brush border of the small intestine, thereby reducing postprandial blood sugar. At present, there are many kinds of hypoglycemic drugs used clinically, and most of them are western medicines. Long-term use will inevitably cause many adverse reactions. Therefore, the development of a safe, effective and inexpensive hypoglycemic traditional Chinese medicine has attracted the attention of many scholars. In recent years, the extraction of substances that can inhibit α-glucosidase from plants, and the study of their separation and purification, structure and related inhibitory mechanism have become the research hotspots of α-glucosidase inhibitors.
其中蜂窝草(Leucaszeylanica)，是绣球防风属唇形科植物。具有疏风散寒，化痰止咳等作用。该植物含有黄酮、萜类成分等多种类型化合物，但对其化学成分的研究报道相对较少，因此，对这种黎药的化学成分的发掘还具有空间。进一步讨论其生源途径显得尤为重要。本项目拟在前期工作的基 础上，进一步加大对海南黎药的化学成分研究。主要研究这种黎药中提取、分离和纯化具有生物活性成分的科学方法和技术；鉴定具有生物活性化合物的分子结构与立体构型；确定具有生物活性部位、组分及单体化合物；这对具有活性新药的开发以及海南黎药的宣传和广泛应用都具有非常重要的意义。Among them, honeycomb grass (Leucaszeylanica) is a plant of the genus Lamiaceae. It has the effects of dispelling wind and cold, resolving phlegm and relieving cough. The plant contains many types of compounds such as flavonoids and terpenoids, but there are relatively few research reports on its chemical constituents. Therefore, there is still room for exploration of the chemical constituents of this li medicine. It is particularly important to further discuss its source of life. This project intends to further increase the research on the chemical components of Hainan Li medicine on the basis of the previous work. Mainly study the scientific methods and technologies for extracting, separating and purifying biologically active ingredients in Li medicine; identify the molecular structure and three-dimensional configuration of biologically active compounds; determine the biologically active sites, components and monomeric compounds; The development of active new drugs and the promotion and wide application of Hainan Li medicine are of great significance.
发明内容Contents of the invention
本发明的目的在于提供蜂窝草中Halimane型二萜化合物及其制备方法与应用，以解决上述背景技术中提出的问题。The object of the present invention is to provide the Halimane type diterpene compound in honeycomb and its preparation method and application, so as to solve the problems raised in the above-mentioned background technology.
为实现上述目的，本发明提供如下技术方案：蜂窝草中Halimane型二萜化合物，其结构式如下：In order to achieve the above object, the present invention provides the following technical scheme: Halimane type diterpene compound in honeycomb grass, its structural formula is as follows:
Figure PCTCN2021127232-appb-000001
Figure PCTCN2021127232-appb-000001
本发明还提供了蜂窝草中Halimane型二萜化合物的制备方法，包括以下步骤：The present invention also provides the preparation method of Halimane type diterpene compound in honeycomb grass, comprising the following steps:
步骤一：将蜂窝草全草风干粉碎后，用乙醇浸泡，得粘稠状棕色浸膏；Step 1: Air-dry and crush the whole honeycomb grass, soak it in ethanol to get a viscous brown extract;
步骤二：将浸膏分散在蒸馏水中得到混悬溶液，对混悬溶液用石油醚萃取3次，合并萃取液，得到石油醚部位；继续用乙酸乙酯萃取3次，合并萃取液，减压浓缩得到乙酸乙酯部位和水相部位；Step 2: Disperse the extract in distilled water to obtain a suspension solution, extract the suspension solution 3 times with petroleum ether, combine the extracts to obtain the petroleum ether part; continue to extract 3 times with ethyl acetate, combine the extracts, and depressurize Concentrate to obtain the ethyl acetate part and the aqueous phase part;
步骤三：对石油醚部位经柱层析、薄层层析、分子筛层析，液相制备，即得。Step 3: prepare the petroleum ether part through column chromatography, thin layer chromatography, molecular sieve chromatography, and liquid phase to obtain the product.
优选的，所述步骤一中，采用体积分数75％的乙醇浸泡。Preferably, in the first step, 75% ethanol by volume is used for soaking.
优选的，所述步骤二中萃取过程中，将浸膏分散在蒸馏水中得到混悬溶液，用石油醚萃取，混悬溶液：石油醚体积比＝1：1，萃取3次，合并萃取液， 减压浓缩得到石油醚部位；继续用乙酸乙酯萃取混悬溶液，混悬溶液：乙酸乙酯体积比＝1：1，萃取3次，合并萃取液，减压浓缩得到乙酸乙酯部位和水相部位。Preferably, during the extraction process in step 2, disperse the extract in distilled water to obtain a suspension solution, extract with petroleum ether, suspension solution: petroleum ether volume ratio = 1:1, extract 3 times, combine the extracts, Concentrate under reduced pressure to obtain the petroleum ether part; continue to extract the suspension solution with ethyl acetate, the suspension solution: ethyl acetate volume ratio = 1:1, extract 3 times, combine the extracts, concentrate under reduced pressure to obtain the ethyl acetate part and water phase parts.
优选的，所述步骤三中经柱层析的条件为：正向硅胶柱层析(CC)，以石油醚-乙酸乙酯作为洗脱剂。Preferably, the condition of the column chromatography in the step three is: forward silica gel column chromatography (CC), using petroleum ether-ethyl acetate as the eluent.
优选的，所述步骤三中薄层层析条件为：以乙酸乙酯体积百分数为5％-40％的石油醚-乙酸乙酯混合溶剂为展开剂。Preferably, the thin-layer chromatography conditions in the step three are as follows: a mixed solvent of petroleum ether-ethyl acetate with a volume percentage of ethyl acetate of 5%-40% is used as a developing solvent.
优选的，所述步骤三中分子筛层析条件为：分子筛为Sephadex LH-20，以氯仿体积百分数为0％-50％的氯仿-甲醇混合溶剂为洗脱剂。Preferably, the molecular sieve chromatography conditions in the third step are: the molecular sieve is Sephadex LH-20, and a chloroform-methanol mixed solvent with a volume percentage of chloroform of 0%-50% is used as the eluent.
液相制备条件为：安捷伦DAD检测器1260LC系列C-18柱进行分离纯化，色谱柱规格：长250mm，内径9.4mm，硅胶粒度5μm，流动相为：甲醇体积分数为68％的甲醇-水混合溶液为洗脱剂。The liquid phase preparation conditions are: Agilent DAD detector 1260LC series C-18 column for separation and purification, chromatographic column specifications: length 250mm, inner diameter 9.4mm, silica gel particle size 5μm, mobile phase: methanol-water mixture with a methanol volume fraction of 68% The solution is the eluent.
本发明还提出所述蜂窝草中Halimane型二萜化合物在制备降糖药物中的应用。The invention also proposes the application of the Halimane-type diterpene compound in the honeycomb grass in the preparation of hypoglycemic drugs.
本发明还提出一种降糖药物，含有所述的蜂窝草中Halimane型二萜化合物。The invention also proposes a hypoglycemic drug, which contains the Halimane type diterpene compound in the honeycomb grass.
本发明的技术效果和优点：本发明提供一种蜂窝草中Halimane型二萜化合物，且具有降糖活性，可应用于制备降糖药物中。制备工艺简单、成本低廉、原料来源广泛。Technical effects and advantages of the present invention: the present invention provides a Halimane-type diterpene compound in honeycomb, which has hypoglycemic activity and can be applied to the preparation of hypoglycemic drugs. The preparation process is simple, the cost is low, and the source of raw materials is extensive.
附图说明Description of drawings
图1为本发明化合物1的 1H- 1H COSY相关信号示意图。 Fig. 1 is a schematic diagram of 1 H- 1 H COZY related signals of compound 1 of the present invention.
图2为本发明化合物1的关键HMBC相关信号示意图。Fig. 2 is a schematic diagram of key HMBC-related signals of Compound 1 of the present invention.
图3为本发明化合物1的 1H NMR谱图(methanol-d 4,400MHz)。 Fig. 3 is the 1 H NMR spectrum (methanol-d 4 , 400 MHz) of Compound 1 of the present invention.
图4为本发明化合物1的 13C NMR谱图(methanol-d 4,100MHz)。 Fig. 4 is the 13 C NMR spectrum (methanol-d 4 , 100 MHz) of Compound 1 of the present invention.
图6为本发明化合物1的DEPT谱图。Fig. 6 is the DEPT spectrum of compound 1 of the present invention.
图5为本发明化合物1的HSQC谱图。Fig. 5 is the HSQC spectrogram of compound 1 of the present invention.
图7为本发明化合物1的COSY谱图。Fig. 7 is the COZY spectrum of compound 1 of the present invention.
图8为本发明化合物1的HMBC谱图。Fig. 8 is the HMBC spectrum of compound 1 of the present invention.
具体实施方式Detailed ways
下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。The following will clearly and completely describe the technical solutions in the embodiments of the present invention with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only some, not all, embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by persons of ordinary skill in the art without making creative efforts belong to the protection scope of the present invention.
实施例1Example 1
蜂窝草中Halimane型二萜化合物的制备方法，包括以下步骤：The preparation method of Halimane type diterpene compound in honeycomb grass, comprises the following steps:
步骤一：将蜂窝草全草风干粉碎后，用75％的乙醇浸泡，得到粘稠状棕色浸膏；Step 1: air-dry and crush the whole honeycomb grass, soak it with 75% ethanol to obtain viscous brown extract;
步骤二：将浸膏分散在蒸馏水中得到混悬溶液，用石油醚萃取，混悬溶液：石油醚体积比＝1：1，萃取3次，合并萃取液，减压浓缩得到石油醚部位；继续用乙酸乙酯萃取混悬溶液，混悬溶液：乙酸乙酯体积比＝1：1，萃取3次，合并萃取液，减压浓缩得到乙酸乙酯部位和水相部位；Step 2: Disperse the extract in distilled water to obtain a suspension solution, extract with petroleum ether, suspension solution: petroleum ether volume ratio = 1:1, extract 3 times, combine the extracts, concentrate under reduced pressure to obtain the petroleum ether part; continue Extract the suspension solution with ethyl acetate, suspension solution: ethyl acetate volume ratio = 1:1, extract 3 times, combine the extracts, concentrate under reduced pressure to obtain the ethyl acetate part and the water phase part;
步骤三：对石油醚部位经柱层析、薄层层析、分子筛层析，液相制备，得到Halimane型二萜化合物，其中，Step 3: Prepare the petroleum ether part through column chromatography, thin layer chromatography, molecular sieve chromatography, and liquid phase to obtain a Halimane type diterpene compound, wherein,
经柱层析的条件为：正向硅胶柱层析(CC)，以石油醚-乙酸乙酯作为洗脱剂；The conditions of column chromatography are: forward silica gel column chromatography (CC), with petroleum ether-ethyl acetate as eluent;
薄层层析条件为：以乙酸乙酯体积百分数为5％的石油醚-乙酸乙酯混合溶剂为展开剂；The thin-layer chromatography conditions are as follows: a mixed solvent of petroleum ether-ethyl acetate with a volume percentage of 5% ethyl acetate is used as a developing solvent;
分子筛层析条件为：分子筛为Sephadex LH-20，以氯仿体积百分数为10％的氯仿-甲醇混合溶剂为洗脱剂；The molecular sieve chromatography conditions are: the molecular sieve is Sephadex LH-20, and the chloroform-methanol mixed solvent with chloroform volume percentage of 10% is the eluent;
液相制备条件为：安捷伦DAD检测器1260 LC系列C-18柱进行分离纯化， 色谱柱规格：长250mm，内径9.4mm，硅胶粒度5μm，流动相为：甲醇体积分数为68％的甲醇-水混合溶液为洗脱剂。The liquid phase preparation conditions are: Agilent DAD detector 1260 LC series C-18 column for separation and purification, chromatographic column specifications: length 250mm, inner diameter 9.4mm, silica gel particle size 5μm, mobile phase: methanol-water with a methanol volume fraction of 68% The mixed solution is the eluent.
实施例2Example 2
蜂窝草中Halimane型二萜化合物的制备方法，包括以下步骤：The preparation method of Halimane type diterpene compound in honeycomb grass, comprises the following steps:
步骤一：将蜂窝草全草风干粉碎后，用75％的乙醇浸泡，得到粘稠状棕色浸膏；Step 1: air-dry and crush the whole honeycomb grass, soak it with 75% ethanol to obtain viscous brown extract;
步骤二：将浸膏分散在蒸馏水中得到混悬溶液，用石油醚萃取，混悬溶液：石油醚体积比＝1：1，萃取3次，合并萃取液，减压浓缩得到石油醚部位；继续用乙酸乙酯萃取混悬溶液，混悬溶液：乙酸乙酯体积比＝1：1，萃取3次，合并萃取液，减压浓缩得到乙酸乙酯部位和水相部位；Step 2: Disperse the extract in distilled water to obtain a suspension solution, extract with petroleum ether, suspension solution: petroleum ether volume ratio = 1:1, extract 3 times, combine the extracts, concentrate under reduced pressure to obtain the petroleum ether part; continue Extract the suspension solution with ethyl acetate, suspension solution: ethyl acetate volume ratio = 1:1, extract 3 times, combine the extracts, concentrate under reduced pressure to obtain the ethyl acetate part and the water phase part;
步骤三：对石油醚部位经柱层析、薄层层析、分子筛层析，液相制备，得到Halimane型二萜化合物，其中，Step 3: Prepare the petroleum ether part through column chromatography, thin layer chromatography, molecular sieve chromatography, and liquid phase to obtain a Halimane type diterpene compound, wherein,
经柱层析的条件为：正向硅胶柱层析，以石油醚-乙酸乙酯作为洗脱剂；The conditions of column chromatography are: forward silica gel column chromatography, using petroleum ether-ethyl acetate as eluent;
薄层层析条件为：以乙酸乙酯体积百分数为20％的石油醚-乙酸乙酯混合溶剂为展开剂；The thin-layer chromatography conditions are as follows: a mixed solvent of petroleum ether-ethyl acetate with a volume percentage of 20% ethyl acetate is used as a developing solvent;
分子筛层析条件为：分子筛为Sephadex LH-20，以氯仿体积百分数为35％的氯仿-甲醇混合溶剂为洗脱剂；The molecular sieve chromatography conditions are: the molecular sieve is Sephadex LH-20, and the chloroform-methanol mixed solvent with a chloroform volume percentage of 35% is the eluent;
液相制备条件为：安捷伦DAD检测器1260 LC系列C-18柱进行分离纯化，色谱柱规格：长250mm，内径9.4mm，硅胶粒度5μm，流动相为：甲醇体积分数为68％的甲醇-水混合溶液为洗脱剂。The liquid phase preparation conditions are: Agilent DAD detector 1260 LC series C-18 column for separation and purification, chromatographic column specifications: length 250mm, inner diameter 9.4mm, silica gel particle size 5μm, mobile phase: methanol-water with a methanol volume fraction of 68% The mixed solution is the eluent.
实施例3Example 3
蜂窝草中Halimane型二萜化合物的制备方法，包括以下步骤：The preparation method of Halimane type diterpene compound in honeycomb grass, comprises the following steps:
步骤一：将蜂窝草全草风干粉碎后，用75％的乙醇浸泡，得到粘稠状棕色浸膏；Step 1: air-dry and crush the whole honeycomb grass, soak it with 75% ethanol to obtain viscous brown extract;
步骤二：将浸膏分散在蒸馏水中得到混悬溶液，用石油醚萃取，混悬溶 液：石油醚体积比＝1：1，萃取3次，合并萃取液，减压浓缩得到石油醚部位；继续用乙酸乙酯萃取混悬溶液，混悬溶液：乙酸乙酯体积比＝1：1，萃取3次，合并萃取液，减压浓缩得到乙酸乙酯部位和水相部位；Step 2: Disperse the extract in distilled water to obtain a suspension solution, extract with petroleum ether, suspension solution: petroleum ether volume ratio = 1:1, extract 3 times, combine the extracts, concentrate under reduced pressure to obtain the petroleum ether part; continue Extract the suspension solution with ethyl acetate, suspension solution: ethyl acetate volume ratio = 1:1, extract 3 times, combine the extracts, concentrate under reduced pressure to obtain the ethyl acetate part and the water phase part;
步骤三：对石油醚部位经柱层析、薄层层析、分子筛层析，液相制备，得到Halimane型二萜化合物，其中，Step 3: Prepare the petroleum ether part through column chromatography, thin layer chromatography, molecular sieve chromatography, and liquid phase to obtain a Halimane type diterpene compound, wherein,
经柱层析的条件为：正向硅胶柱层析，以石油醚-乙酸乙酯作为洗脱剂；The conditions of column chromatography are: forward silica gel column chromatography, using petroleum ether-ethyl acetate as eluent;
薄层层析条件为：以乙酸乙酯体积百分数为40％的石油醚-乙酸乙酯混合溶剂为展开剂；The thin-layer chromatography conditions are as follows: a mixed solvent of petroleum ether-ethyl acetate with a volume percentage of 40% ethyl acetate is used as a developing solvent;
分子筛层析条件为：分子筛为Sephadex LH-20，以氯仿体积百分数为50％的氯仿-甲醇混合溶剂为洗脱剂；The molecular sieve chromatography conditions are: the molecular sieve is Sephadex LH-20, and the chloroform-methanol mixed solvent with a chloroform volume percentage of 50% is the eluent;
液相制备条件为：安捷伦DAD检测器1260 LC系列C-18柱进行分离纯化，色谱柱规格：长250mm，内径9.4mm，硅胶粒度5μm，流动相为：甲醇体积分数为68％的甲醇-水混合溶液为洗脱剂。The liquid phase preparation conditions are: Agilent DAD detector 1260 LC series C-18 column for separation and purification, chromatographic column specifications: length 250mm, inner diameter 9.4mm, silica gel particle size 5μm, mobile phase: methanol-water with a methanol volume fraction of 68% The mixed solution is the eluent.
通过上述3个实施例中的制备方法得到Halimane型二萜化合物，结构式如下：Obtain Halimane type diterpene compound by the preparation method in above-mentioned 3 embodiments, structural formula is as follows:
Figure PCTCN2021127232-appb-000002
Figure PCTCN2021127232-appb-000002
其中，化合物1为新化合物。Among them, compound 1 is a new compound.
化合物理化性质检测数据如下：The physical and chemical properties of the compounds are as follows:
化合物1的NMR数据( 1H NMR 400MHz， 13C NMR 100MHz，methanol-d 4) NMR data of compound 1 ( 1 H NMR 400MHz, 13 C NMR 100MHz, methanol-d 4 )
Figure PCTCN2021127232-appb-000003
Figure PCTCN2021127232-appb-000003
Figure PCTCN2021127232-appb-000004
Figure PCTCN2021127232-appb-000004
Figure PCTCN2021127232-appb-000005
Figure PCTCN2021127232-appb-000005
蜂窝草中Halimane型二萜化合物具有降糖活性的试验Experiment on Hypoglycemic Activity of Halimane-Type Diterpenoids in Honeycomb Plant
试验方法：experiment method:
步骤一：分别配制PNPG底物溶液(4-硝基苯基-α-D-吡喃葡萄糖苷)2.5mM、α-葡萄糖苷酶溶液1U、阿卡波糖溶液1mg/mL和PBS缓冲液pH6.8；Step 1: prepare PNPG substrate solution (4-nitrophenyl-α-D-glucopyranoside) 2.5mM, α-glucosidase solution 1U, acarbose solution 1mg/mL and PBS buffer pH6 respectively .8;
步骤二：依次取已配制好的PBS缓冲液，待测样品(实施例1至3获得的化合物)，α-葡萄糖苷酶溶液和PNPG底物溶液充分混匀，于37℃水浴反应15分钟，空白对照为不添加化合物；Step 2: Take the prepared PBS buffer solution, the sample to be tested (compounds obtained in Examples 1 to 3), α-glucosidase solution and PNPG substrate solution and mix well, and react in a water bath at 37°C for 15 minutes. The blank control is no compound added;
步骤三：然后加入150μL NaCO 3溶液使反应终止； Step 3: Then add 150 μL NaCO 3 solution to terminate the reaction;
步骤四：在405nm波长处测定吸光度(A)值，即在酶的作用下底物释放出的硝基酚量；Step 4: Measure the absorbance (A) value at a wavelength of 405nm, that is, the amount of nitrophenol released from the substrate under the action of the enzyme;
步骤五：平行测定3次，根据下述公式计算出各样品和空白对照的抑制率：抑制率＝[(A对照-A空白)-(A样品-A样品空白)]/(A对照-A空白)×100％，再通过SPSS软件计算IC 50值。 Step 5: Measure in parallel 3 times, calculate the inhibition rate of each sample and blank control according to the following formula: inhibition rate=[(A control-A blank)-(A sample-A sample blank)]/(A control-A Blank) × 100%, and then calculate the IC 50 value by SPSS software.
结果表明各样品具有α-葡萄糖苷酶活性抑制作用，本发明提出的蜂窝草中Halimane型二萜化合物具有降糖活性，因此本发明提出所述蜂窝草中Halimane型二萜化合物在制备降糖药物中的应用以及一种降糖药物其含有所述的蜂窝草中Halimane型二萜化合物。本发明提供的蜂窝草中Halimane型二萜化合物制备工艺简单、成本低廉、原料来源广泛，具有很好的推广意义。The result shows that each sample has α-glucosidase activity inhibitory effect, and the Halimane type diterpene compound in the honeycomb grass that the present invention proposes has hypoglycemic activity, so the present invention proposes that the Halimane type diterpene compound in the honeycomb grass is useful in preparing hypoglycemic drugs and a hypoglycemic drug containing the Halimane type diterpene compound in honeycomb. The preparation process of the Halimane type diterpene compound in honeycomb grass provided by the invention is simple, low in cost, wide in source of raw materials, and has good popularization significance.
最后应说明的是：以上所述仅为本发明的优选实施例而已，并不用于限制本发明，尽管参照前述实施例对本发明进行了详细的说明，对于本领域的 技术人员来说，其依然可以对前述各实施例所记载的技术方案进行修改，或者对其中部分技术特征进行等同替换,凡在本发明的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。Finally, it should be noted that: the above is only a preferred embodiment of the present invention, and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, for those skilled in the art, it still The technical solutions recorded in the foregoing embodiments may be modified, or some of the technical features may be replaced equivalently, and any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included in the within the protection scope of the present invention.

Claims (10)

  1. 蜂窝草中Halimane型二萜化合物，其特征在于，其结构式如下：Halimane type diterpene compound in honeycomb grass, it is characterized in that, its structural formula is as follows:
    Figure PCTCN2021127232-appb-100001
    Figure PCTCN2021127232-appb-100001
  2. 根据权利要求1所述的蜂窝草中Halimane型二萜化合物的制备方法，其特征在于，包括以下步骤：The preparation method of Halimane type diterpene compound in honeycomb according to claim 1, is characterized in that, comprises the following steps:
    步骤一：将蜂窝草全草风干粉碎后，用乙醇浸泡，得粘稠状棕色浸膏；Step 1: Air-dry and crush the whole honeycomb grass, soak it in ethanol to get a viscous brown extract;
    步骤二：将浸膏分散在蒸馏水中得到混悬溶液，对混悬溶液用石油醚萃取3次，合并萃取液，得到石油醚部位；继续用乙酸乙酯萃取3次，合并萃取液，减压浓缩得到乙酸乙酯部位和水相部位；Step 2: Disperse the extract in distilled water to obtain a suspension solution, extract the suspension solution 3 times with petroleum ether, combine the extracts to obtain the petroleum ether part; continue to extract 3 times with ethyl acetate, combine the extracts, and depressurize Concentrate to obtain the ethyl acetate part and the aqueous phase part;
    步骤三：对石油醚部位经柱层析、薄层层析、分子筛层析，液相制备，即得。Step 3: prepare the petroleum ether part through column chromatography, thin layer chromatography, molecular sieve chromatography, and liquid phase to obtain the product.
  3. 根据权利要求2所述的蜂窝草中Halimane型二萜化合物的制备方法，其特征在于：所述步骤一中，采用体积分数75％的乙醇浸泡。The preparation method of Halimane type diterpenoids in honeycomb grass according to claim 2, characterized in that: in said step 1, soaking with ethanol with a volume fraction of 75%.
  4. 根据权利要求2所述的蜂窝草中Halimane型二萜化合物的制备方法，其特征在于：所述步骤二中，萃取过程中，将浸膏分散在蒸馏水中得到混悬溶液，用石油醚萃取，混悬溶液：石油醚体积比＝1：1，萃取3次，合并萃取液，减压浓缩得到石油醚部位；继续用乙酸乙酯萃取混悬溶液，混悬溶液：乙酸乙酯体积比＝1：1，萃取3次，合并萃取液，减压浓缩得到乙酸乙酯部位和水相部位。The preparation method of the Halimane type diterpene compound in honeycomb according to claim 2, is characterized in that: in said step 2, during the extraction process, the extract is dispersed in distilled water to obtain a suspension solution, extracted with petroleum ether, Suspension solution: petroleum ether volume ratio = 1:1, extract 3 times, combine extracts, concentrate under reduced pressure to obtain petroleum ether fraction; continue to extract suspension solution with ethyl acetate, suspension solution: ethyl acetate volume ratio = 1 : 1, extracted 3 times, combined the extracts, concentrated under reduced pressure to obtain the ethyl acetate part and the aqueous phase part.
  5. 根据权利要求2所述的蜂窝草中Halimane型二萜化合物的制备方法，其特征在于：所述步骤三中，经柱层析的条件为：正向硅胶柱层析，以石油醚-乙酸乙酯作为洗脱剂。The preparation method of Halimane type diterpene compound in Honeycomb according to claim 2, is characterized in that: in described step 3, the condition through column chromatography is: forward silica gel column chromatography, with petroleum ether-ethyl acetate Esters as eluents.
  6. 根据权利要求2所述的蜂窝草中Halimane型二萜化合物的制备方法，其特征在于：所述步骤三中，薄层层析条件为：以乙酸乙酯体积百分数为5％-40％的石油醚-乙酸乙酯混合溶剂为展开剂。The preparation method of Halimane type diterpene compound in Honeycomb according to claim 2, is characterized in that: in described step 3, thin-layer chromatography condition is: the petroleum that is 5%-40% with ethyl acetate volume percentage Ether-ethyl acetate mixed solvent was used as developing solvent.
  7. 根据权利要求2所述的蜂窝草中Halimane型二萜化合物的制备方法，其特征在于：所述步骤三中，分子筛层析条件为：分子筛为Sephadex LH-20，以氯仿体积百分数为0％-50％的氯仿-甲醇混合溶剂为洗脱剂。The preparation method of Halimane type diterpene compound in honeycomb according to claim 2, is characterized in that: in described step 3, molecular sieve chromatography condition is: molecular sieve is Sephadex LH-20, is 0%- with chloroform volume percentage 50% chloroform-methanol mixed solvent was used as eluent.
  8. 根据权利要求2所述的蜂窝草中Halimane型二萜化合物的制备方法，其特征在于：所述步骤三中，液相制备条件为：安捷伦DAD检测器1260 LC系列C-18柱进行分离纯化，色谱柱规格：长250mm，内径9.4mm，硅胶粒度5μm，流动相为：甲醇体积分数为68％的甲醇-水混合溶液为洗脱剂。The preparation method of the Halimane type diterpene compound in honeycomb according to claim 2, is characterized in that: in the step 3, the liquid phase preparation conditions are: Agilent DAD detector 1260 LC series C-18 column for separation and purification, Chromatographic column specifications: length 250mm, inner diameter 9.4mm, silica gel particle size 5μm, mobile phase: methanol-water mixed solution with methanol volume fraction 68% as eluent.
  9. 根据权利要求1所述的蜂窝草中Halimane型二萜化合物的应用，其特征在于：所述蜂窝草中Halimane型二萜化合物在制备降糖药物中的应用。The application of the Halimane-type diterpene compound in honeycomb grass according to claim 1, characterized in that: the application of the Halimane-type diterpene compound in the honeycomb grass in the preparation of hypoglycemic drugs.
  10. 一种降糖药物，其特征在于：含有权利要求1所述的蜂窝草中Halimane型二萜化合物。A hypoglycemic drug, characterized in that it contains the Halimane type diterpene compound in honeycomb according to claim 1.
PCT/CN2021/127232 2021-10-29 2021-10-29 Halimane diterpenoid in leucas zeylanica, and preparation method and application thereof WO2023070480A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/CN2021/127232 WO2023070480A1 (en) 2021-10-29 2021-10-29 Halimane diterpenoid in leucas zeylanica, and preparation method and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2021/127232 WO2023070480A1 (en) 2021-10-29 2021-10-29 Halimane diterpenoid in leucas zeylanica, and preparation method and application thereof

Publications (1)

Publication Number Publication Date
WO2023070480A1 true WO2023070480A1 (en) 2023-05-04

Family

ID=86160357

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2021/127232 WO2023070480A1 (en) 2021-10-29 2021-10-29 Halimane diterpenoid in leucas zeylanica, and preparation method and application thereof

Country Status (1)

Country Link
WO (1) WO2023070480A1 (en)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104080466A (en) * 2011-10-21 2014-10-01 韩国海洋科学技术院 Diterpene furanoids compound which inhibits protein tyrosine phosphatase 1B and the use thereof
CN108440292A (en) * 2018-04-03 2018-08-24 中国科学院昆明植物研究所 Different sequence Chinese tallow tree element A-H and its pharmaceutical composition and its application
CN109908133A (en) * 2019-04-04 2019-06-21 山东大学 A kind of pimarane type diterpene is preparing the application in anti-oxidation stress medicine
CN111116329A (en) * 2019-12-11 2020-05-08 海南师范大学 Preparation method and application of isolariciresinol

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104080466A (en) * 2011-10-21 2014-10-01 韩国海洋科学技术院 Diterpene furanoids compound which inhibits protein tyrosine phosphatase 1B and the use thereof
CN108440292A (en) * 2018-04-03 2018-08-24 中国科学院昆明植物研究所 Different sequence Chinese tallow tree element A-H and its pharmaceutical composition and its application
CN109908133A (en) * 2019-04-04 2019-06-21 山东大学 A kind of pimarane type diterpene is preparing the application in anti-oxidation stress medicine
CN111116329A (en) * 2019-12-11 2020-05-08 海南师范大学 Preparation method and application of isolariciresinol

Similar Documents

Publication Publication Date Title
Xu et al. Anti-diabetic effect mediated by Ramulus mori polysaccharides
CN101394858A (en) Intestinal alpha-glucosidase inhibitors and a process for the isolation and use thereof
Obaroakpo et al. Bioactive assessment of the antioxidative and antidiabetic activities of oleanane triterpenoid isolates of sprouted quinoa yoghurt beverages and their anti-angiogenic effects on HUVECS line
WO2023070480A1 (en) Halimane diterpenoid in leucas zeylanica, and preparation method and application thereof
CN105030914B (en) Application of the Ligustrum robust Folum Ilicis extract in alpha-glucosidase restrainer
CN115490637B (en) Preparation method and application of aporphine alkaloid compound
CN107056869A (en) A kind of withanolide class compound and extracting method and application
CN110143989B (en) Ellagitannins alpha-glucosidase inhibitor and preparation method thereof
Peng et al. Chemical components and bioactivity evaluation of extracts from pear (Pyrus Ussuriensis Maxim) fruit
CN108314620A (en) Different sequence chinese tallow tree element i and j and its pharmaceutical composition and its application
CN103005282A (en) Wheat bran extract healthcare food with blood sugar reduction function and preparation method thereof
CN116063313A (en) Halimane diterpenoid compound in honeycomb grass, and preparation method and application thereof
CN106565444A (en) Extraction method and application of phenanthrene compounds from overground part of Chinese yam
CN106749492A (en) A kind of steroid saponin compound and its preparation method and application
CN113200811A (en) Lactarius azulene element, preparation method and application thereof
CN102050862B (en) New honeysuckle chlorogenic acid ester saponin as well as preparation method and use thereof
CN114276339B (en) Sesquilignans compound, and separation method and application thereof
CN106565811B (en) The extracting method of the hypoglycemic active ingredient of Chinese yam aerial part and application
TWI812448B (en) Hydroxyloureirin, production method and use thereof
CN115073374B (en) Alpha-glucosidase inhibitor and preparation method and application thereof
CN114891012B (en) Aporphine alkaloid compound, and extraction method and application thereof
CN116554254B (en) Compound with sedative and insomnia relieving effects and application thereof
CN116693480B (en) Dihydro-fraxinenone A and preparation method and application thereof
CN115141245B (en) Cucurbitane-type tetracyclic triterpene compound with anti-mastitis activity extracted from Chinese hemsleya root, and preparation method and application thereof
CN114569594B (en) Application of schizandrin L in preparation of alpha-glucosidase inhibitor

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 21961845

Country of ref document: EP

Kind code of ref document: A1