CN113896702A - 一种槲皮万寿菊素-3-衍生物及用途 - Google Patents
一种槲皮万寿菊素-3-衍生物及用途 Download PDFInfo
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- quercetagetin
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 34
- 238000006243 chemical reaction Methods 0.000 claims description 16
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 claims description 14
- 150000001875 compounds Chemical class 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- 238000010511 deprotection reaction Methods 0.000 claims description 8
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- 229960001285 quercetin Drugs 0.000 claims description 8
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 claims description 7
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 claims description 7
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
- C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
- C07D311/30—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/116—Heterocyclic compounds
- A23K20/121—Heterocyclic compounds containing oxygen or sulfur as hetero atom
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- Polymers & Plastics (AREA)
- Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Animal Husbandry (AREA)
- Zoology (AREA)
- Botany (AREA)
- Mycology (AREA)
- Health & Medical Sciences (AREA)
- Nutrition Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明提供一种槲皮万寿菊素‑3‑衍生物及用途。一种槲皮万寿菊素‑3‑衍生物,其结构如通式(I)所示,其中,R1为任意基团。本发明对槲皮万寿菊素的C‑3位羟基进行修饰,在其活性,如抗氧化性不受影响的前提下,可以达到优化其理化性质和生物活性的目的,从而进一步拓宽槲皮万寿菊素应用场景,扩大其应用范围。
Description
技术领域
本发明涉及化学技术领域,尤其涉及一种槲皮万寿菊素-3-衍生物及用途。
背景技术
黄酮是一类广泛存在于植物中的多羟基酚类物质。它们在植物体的叶、木、皮、壳和果肉中均有一定含量,水果、谷物表皮中均含有较高植物多酚。研究表明,黄酮类物质具有很好的生物活性,如抗氧化、抗炎、抗过敏、降血压、抗心律失常、抗肿瘤等功效。槲皮万寿菊素是万寿菊花提取叶黄素后产生的万寿菊渣的主要成分,化学名称为3,5,6,7,3’,4’-六羟基黄酮,其结构与槲皮素接近,仅在C-6位上比槲皮素多一个羟基,具有很好的生物活性。
槲皮万寿菊素多个羟基结构的存在使得其脂溶性和水溶性较低,因此限制了其应用,难以达到有效抗氧化浓度阈值。另外较低的脂溶性还导致了槲皮万寿菊素分子不易透过细胞膜脂双层,使得其生物利用度较低,较低的水溶性会限制其在饮料及动物饮水等多方面的用途。
鉴于此,特提出本发明。
发明内容
本发明探究并提供了一种槲皮万寿菊素-3-衍生物及用途,通过对槲皮万寿菊素的C-3位羟基进行修饰,在其活性得到兼顾的同时,还可以达到优化其理化性质和生物活性的目的。
本发明提供了一种槲皮万寿菊素-3-衍生物,其结构如通式(I)所示:
其中,R1为任意基团。
优选地,R1为烷基、杂环基。
具体而言,本发明所述“烷基”指含1-22个碳原子的直链和支链以及环状烃基团,例如C12-22的直链或直链烷基,进一步优选正十一碳烷基、正十三碳烷基、正十五碳烷基、正十七碳烷基、正十九碳烷基、正二十一碳烷基等,或为取代烷基,如羧基烷基。
本发明所述“杂环基”为3-8个原子组成的杂环基,是指包含3-8个环原子的、单价或多价的、饱和或部分不饱和的、非芳香性的单环,其中至少一个环原子选自氮、硫和氧原子。除非另外说明,3-8个原子组成的杂环基可以是碳基或氮基,且-CH2-基团可以任选地被-C(=O)-替代。环的硫原子可以任选地被氧化成S-氧化物。环的氮原子可以任选地被氧化成N-氧化合物。例如葡萄糖基、哌嗪基、C1-C6取代的哌嗪基,如甲基哌嗪基、乙基哌嗪基等。
本发明提供了上述槲皮万寿菊素-3-衍生物的制备方法,包括如下步骤:
1)槲皮万寿菊素与羟基保护剂进行选择性羟基保护反应得到3’,4’,6,7羟基保护化合物;
2)在缚酸剂的作用下,3’,4’,6,7羟基保护化合物与酰化剂进行酰化反应得到3-酯基-3’,4’,6,7羟基保护化合物;
3)3-酯基-3’,4’,6,7羟基保护化合物与羟基脱保护剂进行选择性羟基脱保护反应得到目标化合物。
具体的,所述步骤1)中,所述选择性羟基保护反应在无溶剂下进行,且采用二氯二苯甲烷作为羟基保护剂。发明人经大量研究后发现,上述羟基保护剂可选择性地与槲皮万寿菊素的3’,4’位羟基以及6,7位羟基进行反应,进而使3’,4’以及6,7位羟基得到保护,以便C-3羟基能够更高效与酰化剂进行酰化反应,从而提高目标产物的收率。
和/或,所述槲皮万寿菊素与羟基保护剂的摩尔比为1:(2-10)。
和/或,所述选择性羟基保护反应的温度为20-200℃,优选80-100℃。
所述步骤2)中,缚酸剂选自三级铵、吡啶、DMAP、无机碱中的一种或多种。
和/或,所述酰化剂为R1COX,其中,R1的定义同权利要求1中式(I)中R1的定义,X为卤素。
和/或,所述3’,4’,6,7羟基保护化合物、酰化剂和缚酸剂的摩尔比为1:(1.5-3):(1.5-3)。
和/或,所述酰化反应的温度为0-40℃。
和/或,所述酰化反应在有机溶剂存在下进行,所述有机溶剂选自二氯甲烷、DMF、THT、乙酸乙酯、乙腈、丙酮中的一种或多种。
所述步骤3)中,羟基脱保护剂选自盐酸、磷酸、三氟乙酸、冰醋酸、氨基酸中的一种或多种。
和/或,所述选择性羟基脱保护反应的温度为0-100℃。
和/或,所述选择性羟基脱保护反应在溶剂存在下进行,所述溶剂选自四氢呋喃、DMF、二氯甲烷、甲醇、乙醇、乙酸乙酯、丙酮、水中的一种或多种。
和/或,所述3-酯基-3’,4’,6,7羟基保护化合物、羟基脱保护剂、有机溶剂的质量体积比为1g:(2-100)ml:(2-100)ml。
本发明还提供上述的槲皮万寿菊素-3-衍生物在制备功能食品中的应用。
本发明还提供上述的槲皮万寿菊素-3-衍生物在制备药品中的应用。
本发明还提供上述的槲皮万寿菊素-3-衍生物在制备饲料添加剂中的应用。
基于上述方案,本发明的有益效果如下:
本发明对槲皮万寿菊素的C-3位羟基进行修饰,在其活性,如抗氧化性不受影响的前提下,可以达到优化其理化性质和生物活性的目的,从而进一步拓宽槲皮万寿菊素应用场景,扩大其应用范围。
具体实施方式
以下实施例用于说明本发明,但不用来限制本发明的范围。
以下实施例及对比例中未注明具体技术或条件者,按照本领域内的文献所描述的技术或条件,或者按照产品说明书进行。所用试剂或仪器未注明生产厂商者,均为可通过正规渠道商购买得到的常规产品。
实施例1
0.5ml玻璃反应瓶中加入槲皮万寿菊素(32mg)、二氯二苯甲烷(90mg),在90℃下搅拌反应12h,冷却到室温,用碳酸氢钠水溶液调成中性,乙酸乙酯萃取并减压浓缩,所得产物溶于0.5ml二氯甲烷中,加入棕榈酰氯(45μL)和三乙胺(20μL),室温反应4h,待反应结束后再加入冰乙酸(0.5ml),回流反应12h,待反应结束后用乙酸乙酯进行萃取,浓缩后用二氯甲烷结晶,经过滤、洗涤得到万寿菊素-3-棕榈酸酯(40mg),收率71%。
万寿菊素-3-棕榈酸酯核磁数据:
1HNMR(DMSO-d6):δ12.04(s,1H),10.68(br,1H),9.84(br,1H),9.50(br,1H),8.90(br,1H),7.30(d,J=2.0Hz,1H),7.23(dd,J=8.3,2.0Hz,1H),6.89(d,J=8.3Hz,1H),6.56(s,1H),2.62(t,J=7.4,2H),1.62(m,2H),1.22(m,24H),0.83(m,3H)。
13C NMR(DMSO-d6):175.059,170.612,155.738,153.922,149.095,149.051,146.397,145.457,129.387,129.168,120.368,119.886,115.854,114.957,103.787,93.908,33.142,31.312,29.073,29.044,28.950,28.862,28.738,28.643,28.293,24.327,22.118,13.959ppm。
质谱显示成分为减氢分子离子峰555.28。
脂溶性测定:
20℃下,槲皮万寿菊和槲皮万寿菊素-3-棕榈酸酯在大豆油中溶解度分别为10μg/ml和500μg/ml,与槲皮万寿菊相比,槲皮万寿菊素-3-棕榈酸酯的脂溶性提高了50倍。
DPPH自由基清除能力测定:
用无水乙醇配置2×10-4mol/L的DPPH溶液,配置槲皮万寿菊素-3-棕榈酸酯样品溶液,取DPPH溶液和样品溶液2ml,30℃避光反应30min后在519nm测试吸光度,并计算半数清除率,其中对其进行自由基DPPH清除能力测定,叔丁基对苯二酚(TBHQ)和槲皮万寿菊素做阳性对照,其中槲皮万寿菊-3-棕榈酸酯的IC50值为18.74μmol/ml;TBHQ的IC50值为34.53μmol/ml;槲皮万寿菊素的IC50值为17.57μmol/ml,结果表明:槲皮万寿菊-3-棕榈酸酯具有较优异的自由基清除能力,同时3位取代后不影响槲皮万寿菊素的自由基清除能力。
实施例2
0.5ml玻璃反应瓶中加入加入槲皮万寿菊素(32mg)、二氯二苯甲烷(90mg),在90℃下搅拌反应12h,冷却到室温,用碳酸氢钠水溶液调成中性,乙酸乙酯萃取并减压浓缩,所得产物溶于0.5ml二氯甲烷中,加入4-甲基哌嗪-1-甲酰氯(20mg)和三乙胺(20μL),室温反应4h,待反应结束后在加入250μl乙酸乙酯和250μl冰乙酸,反应4h,待反应结束后用乙酸乙酯进行萃取,浓缩后用二氯甲烷结晶,经过滤、洗涤得到槲皮万寿菊素3-甲基哌嗪(35.5mg),收率80%。
质谱显示成分为减氢分子离子峰443.12。
水溶性测定:
25℃下,槲皮万寿菊和槲皮万寿菊素3-甲基哌嗪在水中溶解度分别为0.6mg/ml和35mg/ml,与槲皮万寿菊相比,槲皮万寿菊素3-甲基哌嗪的水溶性提高了58倍。
按照实施例1记载的方法对槲皮万寿菊素3-甲基哌嗪的自由基DPPH清除能力进行测定,其IC50值为17.37μmol/ml,与槲皮万寿菊清除能力相当,结果表明3位取代后不影响槲皮万寿菊素的自由基清除能力。
实施例3
在二氯二苯甲烷(90mg)中加入槲皮万寿菊素(32mg),在90℃下搅拌反应5h后降温至室温,冷却到室温,体系加入0.5ml二氯甲烷进行稀释溶解,然后加入三乙胺(20μL)和丙二酰氯(50μL),室温反应2h后,加入水(0.5ml)进行水解1h,用0.5ml二氯甲烷进行萃取,二氯甲烷相加入三氟乙酸(0.5ml),25℃反应4h,产品经硅胶纯化得槲皮万寿菊素3-甲酯乙酸30mg,收率73.8%。
质谱显示成分为减氢分子离子峰403.0。
水溶性测定:
25℃下,槲皮万寿菊素3-丙酸在水中溶解度为15mg/ml。
DPPH自由基清除能力测定:
按照实施例1记载的方法对槲皮万寿菊素3-甲酯乙酸的自由基DPPH清除能力进行测定,其IC50值为19.42μmol/ml。
对比例1
在乙酸乙酯(1ml)中加入槲皮万寿菊素(32mg),棕榈酰氯(45μL)和三乙胺(20μL),室温反应4h,反应液加入乙酸乙酯和水后进行萃取,乙酸乙酯相进行干燥旋干后进行硅胶分离,流动相为石油醚:乙酸乙酯:乙醇=15:5:1,得到33mg非定点取代的槲皮万寿菊素棕榈酸酯,收率58.6%,进行质谱检测,质谱显示成分为减氢分子离子峰555.28。
脂溶性测定:
20℃下,非定点取代的槲皮万寿菊素棕榈酸酯在大豆油中溶解度为550μg/ml。
按照实施例1记载的方法对非定点取代的槲皮万寿菊素棕榈酸酯的自由基DPPH清除能力进行测定,其IC50值为27.42μmol/ml。数据显示:槲皮万寿菊素的A环和B环上羟基取代会导致槲皮万寿菊素的自由基清除能力下降。
最后应说明的是:以上实施例仅用以说明本发明的技术方案,而非对其限制;尽管参照前述实施例对本发明进行了详细的说明,本领域的普通技术人员应当理解: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;而这些修改或者替换,并不使相应技术方案的本质脱离本发明各实施例技术方案的精神和范围。
Claims (10)
2.根据权利要求1所述的槲皮万寿菊素-3-衍生物,其特征在于,R1为烷基、杂环基。
3.根据权利要求1或2所述的槲皮万寿菊素-3-衍生物,其特征在于,R1为取代或未取代的C1-C22的直链或支链烷基。
4.根据权利要求1或2所述的槲皮万寿菊素-3-衍生物,其特征在于,R1为葡萄糖基、哌嗪基、C1-C6取代的哌嗪基。
5.一种权利要求1-4任一项所述的槲皮万寿菊素-3-衍生物的制备方法,其特征在于,包括如下步骤:
1)槲皮万寿菊素与羟基保护剂进行选择性羟基保护反应得到3’,4’,6,7羟基保护化合物;
2)在缚酸剂的作用下,3’,4’,6,7羟基保护化合物与酰化剂进行酰化反应得到3-酯基-3’,4’,6,7羟基保护化合物;
3)3-酯基-3’,4’,6,7羟基保护化合物与羟基脱保护剂进行选择性羟基脱保护反应得到目标化合物。
6.根据权利要求5所述的槲皮万寿菊素-3-衍生物的制备方法,其特征在于,所述步骤1)中,所述选择性羟基保护反应在无溶剂下进行,且采用二氯二苯甲烷作为羟基保护剂。
7.根据权利要求5或6所述的槲皮万寿菊素-3-衍生物的制备方法,其特征在于,所述选择性羟基保护反应的温度为20-200℃,优选80-100℃。
8.权利要求1-4任一种所述的槲皮万寿菊素-3-衍生物在制备功能食品中的应用。
9.权利要求1-4任一项所述的槲皮万寿菊素-3-衍生物在制备药品中的应用。
10.权利要求1-4任一项所述的槲皮万寿菊素-3-衍生物在制备饲料添加剂中的应用。
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CN115819390A (zh) * | 2022-10-28 | 2023-03-21 | 晨光生物科技集团股份有限公司 | 一种槲皮万寿菊素脂溶性衍生物的制备方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1466454A (zh) * | 2000-07-28 | 2004-01-07 | ���·�ķ��˾ | 治疗普通感冒、过敏性鼻炎和呼吸道相关感染的症状的方法 |
EP2468741A1 (en) * | 2010-12-16 | 2012-06-27 | Bel/Novamann International s.r.o. | Novel quercetin derivatives, their preparation, pharmaceutical compositions containing them and their use |
CN104387358A (zh) * | 2014-10-27 | 2015-03-04 | 广东东阳光药业有限公司 | 淫羊藿苷类化合物及其应用 |
-
2021
- 2021-10-29 CN CN202111272595.2A patent/CN113896702A/zh active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1466454A (zh) * | 2000-07-28 | 2004-01-07 | ���·�ķ��˾ | 治疗普通感冒、过敏性鼻炎和呼吸道相关感染的症状的方法 |
EP2468741A1 (en) * | 2010-12-16 | 2012-06-27 | Bel/Novamann International s.r.o. | Novel quercetin derivatives, their preparation, pharmaceutical compositions containing them and their use |
CN104387358A (zh) * | 2014-10-27 | 2015-03-04 | 广东东阳光药业有限公司 | 淫羊藿苷类化合物及其应用 |
Non-Patent Citations (2)
Title |
---|
ANTONELLA SAIJA等: ""’In vitro’ antioxidant and photoprotective properties and interaction with model membranes of three new quercetin esters"", 《EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS》 * |
CHENJUAN LU等: ""Synthesis and Bioactivity of Quercetin Aspirinates"", 《BULL. KOREAN CHEM. SOC.》 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115819390A (zh) * | 2022-10-28 | 2023-03-21 | 晨光生物科技集团股份有限公司 | 一种槲皮万寿菊素脂溶性衍生物的制备方法 |
CN115819390B (zh) * | 2022-10-28 | 2024-06-14 | 晨光生物科技集团股份有限公司 | 一种槲皮万寿菊素脂溶性衍生物的制备方法 |
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