CN103819438B - 柚皮苷一步法制备芹菜素新技术 - Google Patents
柚皮苷一步法制备芹菜素新技术 Download PDFInfo
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- CN103819438B CN103819438B CN201410042942.6A CN201410042942A CN103819438B CN 103819438 B CN103819438 B CN 103819438B CN 201410042942 A CN201410042942 A CN 201410042942A CN 103819438 B CN103819438 B CN 103819438B
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- KZNIFHPLKGYRTM-UHFFFAOYSA-N apigenin Chemical compound C1=CC(O)=CC=C1C1=CC(=O)C2=C(O)C=C(O)C=C2O1 KZNIFHPLKGYRTM-UHFFFAOYSA-N 0.000 title claims abstract description 54
- XADJWCRESPGUTB-UHFFFAOYSA-N apigenin Natural products C1=CC(O)=CC=C1C1=CC(=O)C2=CC(O)=C(O)C=C2O1 XADJWCRESPGUTB-UHFFFAOYSA-N 0.000 title claims abstract description 50
- 235000008714 apigenin Nutrition 0.000 title claims abstract description 50
- 229940117893 apigenin Drugs 0.000 title claims abstract description 50
- 239000001606 7-[(2S,3R,4S,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-5-hydroxy-2-(4-hydroxyphenyl)chroman-4-one Substances 0.000 title claims abstract description 27
- 238000000034 method Methods 0.000 title claims abstract description 27
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- RPMNUQRUHXIGHK-PYXJVEIZSA-N apigenin 7-O-neohesperidoside Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=C2C(=O)C=C(C=3C=CC(O)=CC=3)OC2=C1 RPMNUQRUHXIGHK-PYXJVEIZSA-N 0.000 description 3
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Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/582—Recycling of unreacted starting or intermediate materials
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
柚皮苷一步法制备芹菜素新技术，该技术经以下步骤：一锅烩反应；浓缩物的制备；粗品制备；精品制备；干燥，粉碎，检测，混合，包装。用较为廉价的溶剂替代现有的溶剂，且不影响反应，目前已寻找到合适的溶剂；脱氢试剂在反应中的用量大幅下降。反应过程中，在反应釜上安装自动控温仪，避免了以前温度的上升或下降靠人工操作，极大提高了生产效率；反应终点的判断以高效液相控制，极大的提高了反应的精确性，反应条件温和，时间短，收率和纯度均较高，无环境污染问题，生产成本大幅降低。
Description
技术领域
本发明涉及柚皮苷一步法制备芹菜素新技术
背景技术
芹菜素(Apigenin)，别名：4′,5,7-三羟基黄酮，芹黄素；黄色针状结晶(吡啶水溶液)，几乎不溶于水，部分溶于热酒精，溶于稀KOH溶液。化学名：5,7-Dihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one；分子式：C15H10O5；分子量：270.24；熔点345-350℃，来源于伞形科植物旱芹ApiumgraveolensL.var.dulceDC.叶，此外广泛存在于多种水果、蔬菜、豆类和茶叶，玄参科植物水蔓青，蓼科虎杖，百合科毛叶藜芦，松科植物中。
公元前9世纪荷马史诗中首次提到野生芹菜被应用在医学上，公元7世纪中国从尼泊尔统治者送来的礼品中得到了芹菜这种植物。然而，芹菜作为蔬菜广泛食用是在中世纪，18世纪欧洲作为蔬菜食用，19世纪初引到美国。中华大地的芹菜分为旱芹和水芹。旱芹生于旱地，口感较差，但药用功能较强，水芹含有多种游离氨基酸、芳香油、甘露糖及多种维生素，营养丰富，清香扑鼻，可增进食欲，促进血液循环和健脑作用。芹菜叶中矿物质、维生素的含量高；叶柄中水份高，热量低；种子含蛋白质、脂肪、维生素、钙、磷、镁、钾、铁和锌，热量高。芹菜中还含有芹菜素、佛手苷内酯、糖类、有机酸、挥发油等。挥发油中的α-芹子烯对大脑中枢神经有安定和抗痉挛作用；挥发油中的丁基苯酸是旱芹特殊气味的来源。在欧美，芹菜可用于消除水肿，吃了芹菜有利尿作用。
芹菜中的重要成分芹菜素能降压和影响中枢神经，还有一定的扩张末梢血管的作用，这与降压作用也有一定关系。芹菜素能降低大鼠癫痫发作的程度和次数，延长潜伏期，对大脑顶叶皮层细胞，胶质细胞，和小脑细胞有一定的保护作用，能对抗震颤素引起的中枢性震颤，能对抗可卡因引起的兴奋，具有保护心脏的作用以及治疗帕金森氏症的效果。
目前，国内外制备芹菜素有两种方式：天然提取和半合成。半合成是直接从柚皮素制备或从柚皮苷经两步反应得到芹菜素。柚皮苷制备柚皮素，柚皮素再制备芹菜素，或者柚皮苷制备野漆树苷，再由野漆树苷制备芹菜素。无论是从柚皮素直接制备还是从柚皮苷开始制备，若采用柚皮苷为原料都要经过两步反应才能制备，而且碘的用量较大。天然提取步骤繁杂，收率低。综观国内外文献，黄酮类化合物的氧化脱氢大致有三种方式：溴脱氢；碘脱氢；NBS／过氧化甲苯酰脱氢。1)溴水对黄酮类化合物脱氢分两步反应，工艺繁琐，条件复杂，而且要用到有毒试剂溴水，成本高；溴气对黄酮类化合物脱氢，收率低，且要用到醋酐，二氯甲烷，试剂较多，操作困难。2)NBS／过氧化甲苯酰对黄酮类化合物脱氢，工艺复杂，大体分为三个步骤：①母核乙酰化以保护所有羟基；②母核2、3位双键的生成以氧化剂或溴化剂处理乙酰化母核；③母核乙酰基的脱除以碱的稀醇溶液处理上述产物脱除乙酰基，需要特殊试剂，成本较高，收率低，都不适合工业化生产。3)碘对黄酮类化合物脱氢，采用碘／吡啶脱氢，只有一步反应，收率和含量较高，但成本较高，主要是碘的用量太大，如何降低碘的用量成为技术的核心。传统工艺的主要特点是工艺路线复杂、生产周期长、收率低、成本高。野漆树苷制备芹菜素，目前条件苛刻，需要特殊设备，加压高温下长时间反应，收率和纯度不高，环境污染大。
本发明采用柚皮苷为原料一步法制备芹菜素，一锅烩反应中加入合适的辅料使得柚皮苷经过一个步骤直接得到芹菜素，将原本需要两个操作步骤的反应一步进行，大大缩短反应步骤，反应条件温和，时间短，收率和纯度均较高，无环境污染问题，尤其是关键试剂的用量只有目前传统工艺的1～5％，极大的降低了生产成本。
发明内容
第一一锅烩反应：一定量的柚皮苷溶于计量的溶剂中，加入辅料，在一定温度下反应，高效液相检测控制反应终点，得到芹菜素反应液。
第二粗品制备：反应液呈红棕色，减压浓缩，得到浓缩物，加入纯化水充分搅拌，过滤，滤饼再加入纯化水搅成糊状，沉淀，过滤，得到沉淀物。
第三精品制备：芹菜素粗品以一定量的溶剂溶解后，加入活性炭脱色，过滤，浓缩，结晶，离心，得到芹菜素湿的精品；或者滤液调酸性，沉淀，压滤，洗涤，得到芹菜素湿的精品。
第三精品干燥：将芹菜素湿品转移到干燥机中干燥，烘干后称重。
第四成品粉碎，检测，混合，包装：将干燥后的香叶木素用粉碎机粉碎，粉碎完成后取样检测，混合，包装。
具体实施方式
方式一：500Kg反应釜中，加入400.0Kg吡啶，缓缓加入柚皮苷100.0kg，加入辅料A1.0～5.0kg，辅料B1.0～3.0kg和辅料C0.5～2.5kg，搅拌下缓慢加热到90～110℃，此温度下反应5～10h。取样品检测芹菜素的含量，当柚皮苷含量低于0.5％后停止反应，得到芹菜素的反应液。该反应液在75～95℃，真空度为-(0.01～0.06)Mpa下回收溶剂，得到稠膏状反应物，在此反应物中加入300～800kg纯化水，微微加热，充分搅拌成糊状后过滤，得到黄色滤饼，将滤饼以纯化水洗涤，得到芹菜素粗品。将芹菜素粗品投入精制罐中加入250～500L乙醇，充分搅拌，加热溶解，加入1.5～2.5kg活性炭，加热至50～60℃保温30min，过滤，滤液呈清亮黄色，在低于20℃下结晶10～24h，抽滤，滤饼用纯净水约3×500L洗涤，压滤干，得芹菜素湿的精品，转移到双锥回转真空干燥机中，温度60±2℃干燥。将干燥后的芹菜素粉碎，粉碎完成后交中间站检测。确定混批批次加入到总混机，以2r／min的转速旋转30min，混合完成。物料分装在聚乙烯包装袋中，取样检测，扎封口，套第2层包装袋，扎封口，然后从传递窗口转移到外包装间，外包，贴签入库。
方式二：1000Kg反应釜中，加入600～800Kg二甲基甲酰胺，将柚皮苷150kg缓慢加入反应釜中，充分搅拌，加热溶解，再加入辅料A3.0～10.0kg，辅料B3.0～7.0kg，辅料C1.5～3.5kg，充分搅拌，缓缓加热到90～110℃，在此温度下反应5～8h，取反应液检测芹菜素的含量，当柚皮苷含量低于0.5％后停止反应，得到芹菜素反应液。在80～95℃，真空度为-(0.01～0.05)Mpa下浓缩该反应液，得到芹菜素浓缩液，在此浓缩液中加入800～1500L纯化水充分搅拌30min，离心过滤，得浅黄色滤饼，将滤饼以500～800L纯化水搅成糊状，过滤，得到芹菜素粗品。将此芹菜素粗品投入精制罐中，加入1000～1500L纯化水加热至40～60℃，充分搅拌成糊状后，加入氢氧化钾溶液80～180L，充分搅拌溶解，加入1.5～2.5kg活性炭在40～60℃保温30min，过滤，滤液用醋酸调pH5～6后沉淀5～12h，压滤，滤饼用纯净水约3×800L洗涤，得芹菜素湿的精品，转移到双锥回转真空干燥机中，温度60±2℃干燥。将干燥后的芹菜素粉碎，粉碎完成后交中间站检测。确定混批批次加入到总混机，以2r／min的转速旋转30min，混合完成。物料分装在聚乙烯包装袋中，取样检测，扎封口，套第2层包装袋，扎封口，然后从传递窗口转移到外包装间，外包，贴签入库。
Claims (6)
1.一种柚皮苷一步法制备芹菜素的方法，其特征在于，以柚皮苷为原料，该方法依次经以下步骤：
(1)一锅烩反应：柚皮苷在溶剂A中溶解后，加入脱氢试剂B，辅料C在一定温度下反应，得到芹菜素反应液，所述的溶剂A为吡啶、二甲基甲酰胺、甲酰胺、吗啉或异戊醇中之一；脱氢试剂B为碘、溴水中之一；辅料C为碳酸钠、碳酸氢钠、氢氧化钠或氢氧化钾中之一；柚皮苷与溶剂A的质量比(w/w)为1∶1～1∶6；柚皮苷与脱氢试剂B的质量比(w/w)为1∶0.01～1∶0.05；柚皮苷与辅料C的质量比(w/w)为1∶0.03～1∶0.1；反应温度为80～110℃；
(2)浓缩物的制备：将反应好的反应液在减压下浓缩；
(3)粗品制备：芹菜素浓缩物中加入纯化水充分搅拌，压滤，滤饼再以纯化水洗涤，得到芹菜素粗品；
(4)精品制备：方法一：芹菜素湿的粗品烘干，加入精制釜中，加入溶剂，搅拌下加热溶解，加入活性炭脱色，过滤，滤液沉淀，过滤，洗涤，得芹菜素湿的精品；方法二：步骤(3)中的湿品直接采用碱水溶解，加活性炭脱色，过滤去不溶物，得到纯净的水液，调节酸碱度，沉淀，抽滤，洗涤，干燥，得到芹菜素湿的精品；
(5)干燥，粉碎，检测，混合，包装：芹菜素湿的精品在干燥机中干燥，粉碎后取样检测，混合包装后入库。
2.如权利要求1所述的一种柚皮苷一步法制备芹菜素的方法，其特征在于，步骤(2)中浓缩温度为70～100℃，浓缩真空度为-(0.01～0.06)Mpa。
3.如权利要求1所述的一种柚皮苷一步法制备芹菜素的方法，其特征在于，步骤(3)中浓缩物中搅拌下加入纯化水，搅成稀糊状，压滤，水洗，水洗液成无色为止。
4.如权利要求1所述的一种柚皮苷一步法制备芹菜素的方法，其特征在于，步骤(4)的方法一中的芹菜素粗品以5～10倍量(w/w)的甲醇或乙醇加热溶解，加入0.3～0.6倍量(w/w)的活性炭脱色，浓缩，低温结晶，抽滤，洗涤，干燥，得到芹菜素精品。
5.如权利要求1所述的一种柚皮苷一步法制备芹菜素的方法，其特征在于，步骤(4)的方法二中的湿品直接采用碱水溶解，加活性炭脱色，过滤去不溶物，得到纯净的芹菜素溶液，调节酸碱度，沉淀，压滤，洗涤，干燥，得到芹菜素精品。
6.如权利要求1所述的一种柚皮苷一步法制备芹菜素的方法，其特征在于，步骤(4)的方法二中碱液为1～30％氢氧化钠或氢氧化钾中之一；所用酸液为硫酸，盐酸，醋酸，磷酸中之一；pH值调节至2～7。
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