4-甲酰基苯基(2,3,4,6-O-四乙酰基)-β-D-葡萄糖苷衍生物的有效合成
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摘要
为克服目前合成方法存在收率较低,反应时间长、产品分离困难等不足,本文以β-D-葡萄糖、乙酰溴为原料,经乙酰化、溴代反应合成了糖基体2,3,4,6-O-四乙酰基-α-D-溴代葡萄糖,再与4-羟基苯甲醛衍生物经糖苷化反应合成了5种4-甲酰基苯基(2,3,4,6-O-四乙酰基)-β-D-葡萄糖苷衍生物。在合成4-甲酰基苯基(2,3,4,6-O-四乙酰基)-β-D-葡萄糖苷衍生物的过程中,采用10%(质量分数) Na OH溶液为缚酸剂,三(3,6-二氧杂庚基)胺(TDA-1)为相转移催化剂,反应物的收率为61%～69%,并应用核磁共振技术确定了产品的结构。该方法具有产品收率较高,反应温和、操作简单等优点。
In order to overcome the low yield,long reaction time,and the difficult product separation in current methods,2,3,4,6-O-tetraacetyl-α-D-glucopyranosyl bromide(1) was firstly prepared from β-Dglucose and acetyl bromide via acetylation and bromination. Then,five kinds of 4-formylphenyl(2,3,4,6-Otetraacetyl)-β-D-glucoside derivatives were obtained via glycosylation between intermediate 1 and4-hydroxybenzaldhyde derivatives. The yields of products reached 61% ～ 69% when 10%(mass fraction)NaOH solution and tris(3,6-dioxaheptyl) amine(TDA-1) were used as base and phase transfer catalyst,respectively. The obtained compounds were confirmed by nuclear magnetic resonance(NMR). This method shows advantages in high yield,mild conditions and simple operation.
In order to overcome the low yield,long reaction time,and the difficult product separation in current methods,2,3,4,6-O-tetraacetyl-α-D-glucopyranosyl bromide(1) was firstly prepared from β-Dglucose and acetyl bromide via acetylation and bromination. Then,five kinds of 4-formylphenyl(2,3,4,6-Otetraacetyl)-β-D-glucoside derivatives were obtained via glycosylation between intermediate 1 and4-hydroxybenzaldhyde derivatives. The yields of products reached 61% ～ 69% when 10%(mass fraction)NaOH solution and tris(3,6-dioxaheptyl) amine(TDA-1) were used as base and phase transfer catalyst,respectively. The obtained compounds were confirmed by nuclear magnetic resonance(NMR). This method shows advantages in high yield,mild conditions and simple operation.
引文
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[16]YANG Qinggang,ZHAO Hong,NIE Dong,et al. Facile Preparation of Acetobromoglucose and Acetobromorhamnose[J]. J Fine Chem,2017,34(8):949-953(in Chinese).杨青刚,赵洪,聂东,等.溴代乙酰葡萄糖和溴代乙酰鼠李糖的便捷合成[J].精细化工,2017,34(8):949-953.
[17]LI Yuwen,LI Yingxia,ZHANG Wei,et al. A Convenient One-Pot Preparation of Acetylated Glycopyranosyl Bromides[J].Chinese J Org Chem,2004,24(4):438-439(in Chinese).李玉文,李英霞,张伟,等.一锅法制备全乙酰吡喃溴代糖[J].有机化学,2004,24(4):438-439.
[18]DENG Xiaojuan,WAN Qianhong. Synthesis and Application of 2,3,4,6-Tetra-O-acetyl-β-D-glycosyl Isothiocyanate[J]. J Fine Chem,2005,22(4):307-310(in Chinese).邓小娟,万谦宏. 2,3,4,6-四-O-乙酰基-β-D-吡喃葡萄糖基异硫氰酸酯的合成与应用[J].精细化工,2005,22(4):307-310.
[19]Poalasek C A,Wu J,Stripe W A,et al.[13C]-Enriched Methyl Aldopyranosides:Structural Interpretations of13C-SpinCoupling Constants and1H Chemical Shifts[J]. J Am Chem Soc,1995,117:8635-8644.
[2]WANG Yingying,TIAN Leiyu,YANG Yan,et al. Research Progress in Natural Allopyranosides[J]. Acta Pharmacol Sin,2017,52(3):378-389(in Chinese).王莹莹,田雷瑜,杨燕,等.天然阿洛糖苷的研究进展[J].药学学报,2017,52(3):378-389.
[3]ZHU Qianli,LI Ying,LI Jing,et al. Synthesis and Sedation Activity of 4-Substituted Methylene Phenyl-β-D-allosupranoside[J]. West China J Pharm Sci,2008,23(1):12-16(in Chinese).祝钱莉,李颖,李静,等. 4-取代亚甲基苯基-β-D-吡喃阿洛糖苷的合成及其镇静活性[J].华西药志,2008,23(1):12-16.
[4]Wen H,Lin C L,Que L,et al. Synthesis and Biological Evaluation of Helicid Analogues as Novel Acetylcholinesterase Inhibitors[J]. Eur J Med Chem,2008,43(1):166-173.
[5]LIU Min,LI Ying,YIN Shufan. Synthesis and Calm Activity of 3-(4-β-D-Allopyranosyloxyphenyl)-4-aryl-5-aryl-1,2,4-oxadiazoline[J]. Chinese J Org Chem,2008,28(2):348-352(in Chinese).刘敏,李颖,尹述凡. 3-(4-β-D-吡喃阿洛糖苷-苯基)-4-芳基-5-芳基-1,2,4-噁二唑啉的合成及其镇静活性的研究[J].有机化学,2008,28(2):348-352.
[6]LI Jialin,FAN Bo,LUO Hualing,et al. Synthesis and Calm Activity of 2-(4-β-D-Allopyranosyloxyphenyl)-5-substitutedaryl-1,3,4-oxadiazoles[J]. Chinese J Org Chem,2011,31(1):110-114(in Chinese).李家林,樊波,罗华玲,等. 2-(4-β-D-吡喃阿洛糖苷-苯基)-5-取代芳基-1,3,4-噁二唑的合成及镇静活性研究[J].有机化学,2011,31(1):110-114.
[7]Dahmen J,Frejd T,Magnusson G,et al. Boron Trifluoride Etherate-Induced Glycosidation:Formation of Alkyl Glycosides and Thioglycosides of 2-Deoxy-2-phthalimidoglycopyranoses[J]. Carbohydr Res,1983,114(2):328-330.
[8]Joachim A,Heribert W,Tobias H,et al. Utilizing Genetically Engineered Bacteria to Produce Plant-Specific Glucosides[J]. Biotech Bioeng,2001,76(2):126-131.
[9]Schimidt R R. New Methods for the Synthesis of Glycosides and Oligosaccharides—Are There Alternatives to the KoenigsKnorr Method?[J]. Angew Chem Int Ed,1986,25(2):212-235.
[10]Laurent B,Guyla D,Nicholas B D,et al. Dde as a Protecting Group for Carbohydrate Synthesis[J]. J Carbohydr Chem,2006,22(1):1-18.
[11] LIANG Juan,WENG Weizhi,SONG Jian. Synthesis of(2,3-Dimethoxy-6-Formyl)Phenyl-β-D-Glucoside[J]. J Fine Chem,2017,34(5):596-600(in Chinese).梁娟,翁伟智,宋健.(2,3-二甲氧基-6-甲酰基)苯基-β-D-葡萄糖苷的合成[J].精细化工,2017,34(5):596-600.
[12]Alexander M,Lester S M. Phase-Transfer Catalysed Permanganate Oxidations Using Tris[2-(2-methoxyethoxy)ethyl]amine(Tda-1)[J]. Synth Commun,1987,17(6):647-655.
[13]XU Zhaohui,YAN Nan,ZHOU Peng,et al. Synthesis of Cyclopentanol Catalyzed by Niobic Acid[J]. Petrochem Technol,2010,39(1):28-31(in Chinese).许招会,严楠,周鹏,等.铌酸催化合成环戊醇[J].石油化工,2010,39(1):28-31.
[14]LEI Yingjie,YANG Yicheng. Synthesis of Isoflavone 7-O-Glucosides Catalyzed with Tri(3,6-dioxaheptyl)amine[J].Chinese J Appl Chem,2009,26(3):306-310(in Chinese).雷英杰,杨易成.三(3,6-二氧杂庚基)胺催化合成异黄酮7-O-葡萄糖糖苷[J].应用化学,2009,26(3):306-310.
[15]LEI Yingjie,YANG Liang,OUYANG Jie. Synthesis of Flavone 7-O-Glucosides in the Presence of Tri(3,6-dioxaheptyl)amine[J]. Chem Reagents,2009,31(10):831-834,836(in Chinese).雷英杰,杨亮,欧阳杰.三(3,6-二氧杂庚基)胺催化合成黄酮糖苷的研究[J].化学试剂,2009,31(10):831-834,836.
[16]YANG Qinggang,ZHAO Hong,NIE Dong,et al. Facile Preparation of Acetobromoglucose and Acetobromorhamnose[J]. J Fine Chem,2017,34(8):949-953(in Chinese).杨青刚,赵洪,聂东,等.溴代乙酰葡萄糖和溴代乙酰鼠李糖的便捷合成[J].精细化工,2017,34(8):949-953.
[17]LI Yuwen,LI Yingxia,ZHANG Wei,et al. A Convenient One-Pot Preparation of Acetylated Glycopyranosyl Bromides[J].Chinese J Org Chem,2004,24(4):438-439(in Chinese).李玉文,李英霞,张伟,等.一锅法制备全乙酰吡喃溴代糖[J].有机化学,2004,24(4):438-439.
[18]DENG Xiaojuan,WAN Qianhong. Synthesis and Application of 2,3,4,6-Tetra-O-acetyl-β-D-glycosyl Isothiocyanate[J]. J Fine Chem,2005,22(4):307-310(in Chinese).邓小娟,万谦宏. 2,3,4,6-四-O-乙酰基-β-D-吡喃葡萄糖基异硫氰酸酯的合成与应用[J].精细化工,2005,22(4):307-310.
[19]Poalasek C A,Wu J,Stripe W A,et al.[13C]-Enriched Methyl Aldopyranosides:Structural Interpretations of13C-SpinCoupling Constants and1H Chemical Shifts[J]. J Am Chem Soc,1995,117:8635-8644.