TW201945382A - Xylose derivatives and process for preparation thereof - Google Patents
Xylose derivatives and process for preparation thereof Download PDFInfo
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本發明係關於一種合成木醣衍生物之新方法,以及由其製備之新木醣衍生物。The present invention relates to a new method for synthesizing a xylose derivative and a new xylose derivative prepared therefrom.
綠色化學定義為化學產品及程序的環境友善設計。其為化學研究及工程化的哲學,鼓勵開發可將有害物質的使用及生成最小化的產品及程序。相關實例包括:減少毒性廢棄物,使用可再生原料,進行環境條件反應以降低能量消耗,使用較小量的觸媒,及達成觸媒的高回收百分率等等。綠色化學尋求減少及避免其來源處之污染並應用至生化、有機化學、無機化學、物理化學、分析化學以及甚至碳水化合物化學。最常見地,其著重在工業應用上,諸如將有害廢棄物最小化及效率最大化。Green chemistry is defined as the environmentally friendly design of chemical products and processes. Its philosophy of chemical research and engineering encourages the development of products and procedures that minimize the use and generation of hazardous substances. Relevant examples include: reducing toxic waste, using renewable raw materials, conducting environmental conditions to reduce energy consumption, using smaller amounts of catalyst, and achieving high percentage recovery of catalysts, etc. Green chemistry seeks to reduce and avoid pollution at its source and applies it to biochemistry, organic chemistry, inorganic chemistry, physical chemistry, analytical chemistry, and even carbohydrate chemistry. Most commonly, it focuses on industrial applications, such as minimizing hazardous waste and maximizing efficiency.
最近,水溶性均質觸媒之發展有助於經濟的綠色化學。由於水溶性觸媒容易自有機相分離,其等避免了使用有機溶劑且具成本效益及環境友善性。通常,綠色化學方法需要以下特徵:(1) 使用無毒觸媒及溶劑;及(2) 使用可再生資源來合成化學化合物。Recently, the development of water-soluble homogeneous catalysts has contributed to economic green chemistry. Since water-soluble catalysts are easily separated from the organic phase, they avoid the use of organic solvents and are cost-effective and environmentally friendly. Generally, green chemical methods require the following characteristics: (1) the use of non-toxic catalysts and solvents; and (2) the use of renewable resources to synthesize chemical compounds.
在最近幾年,醣化學在醫學應用上已被廣為接受,諸如生物材料及藥物合成。醣類藥物用來治療癌症、糖尿病、AIDS、流行性感冒、細菌感染及類風濕性關節炎。近年來已針對醣類疫苗進行卓越的研究。然而,大多數的醣類藥物源自天然,諸如植物、動物及微生物之多醣及醣苷。In recent years, sugar chemistry has been widely accepted in medical applications, such as biomaterials and pharmaceutical synthesis. Sugars are used to treat cancer, diabetes, AIDS, influenza, bacterial infections and rheumatoid arthritis. Excellent research on carbohydrate vaccines has been performed in recent years. However, most carbohydrate drugs are derived from natural sources such as polysaccharides and glycosides from plants, animals, and microorganisms.
木醣是第一個從木材分離出的糖,其分類為醛戊醣類的單醣。其衍生自半纖維素,生質主要成份之一。據報告,半纖維素的酸催化降解產生糠醛。此外,由於木醣不含卡路里,其可用作減肥食品。木醣及木醣衍生物可應用在各種領域。具體而言,木醣及其衍生物可應用在綠色化學產業。Xylose was the first sugar isolated from wood and was classified as a monosaccharide of aldopenoses. It is derived from hemicellulose, one of the main ingredients of biomass. It has been reported that acid-catalyzed degradation of hemicellulose produces furfural. In addition, since xylose does not contain calories, it can be used as a diet food. Xylose and xylose derivatives can be used in various fields. Specifically, xylose and its derivatives can be applied in the green chemical industry.
然而,需要經由綠色化學方法發展經濟及有效率的方法以獲得各種木醣衍生物。However, there is a need to develop economical and efficient methods to obtain various xylose derivatives via green chemical methods.
因此,本發明提供一種用於在水相中並且在有機金屬觸媒存在下合成木醣衍生物之新方法。經由該方法,易於修改木醣以自天然獲得新木醣衍生物。由於可回收觸媒且用水作溶劑,該反應是環境友善且經濟的。木醣可經修改以獲得各種官能基,其可影響有機體及/或使其可應用在生物材料中。Therefore, the present invention provides a new method for synthesizing a xylose derivative in an aqueous phase and in the presence of an organometallic catalyst. Through this method, it is easy to modify xylose to obtain a new xylose derivative from nature. Due to the recyclable catalyst and the use of water as a solvent, the reaction is environmentally friendly and economical. Xylose can be modified to obtain various functional groups that can affect the organism and / or make it applicable to biological materials.
在一方面,本發明提供具有通式I之木醣衍生物:式I, 其中(R)m中之m為1至4之整數;R為CH3 、OCH3 、或一鹵素原子。In one aspect, the invention provides xylose derivatives having the general formula I: Formula I, wherein m in (R) m is an integer from 1 to 4; R is CH 3 , OCH 3 , or a halogen atom.
在本發明之具體實施例中,木醣衍生物為選自由以下組成之群組中之一者:2-(4'-氯基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物1);2-(4'-甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物2);2-(4'-甲氧基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物3);2-(2'-甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物4);2-(2'-氯基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物5);2-(2'-甲氧基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物6);2-(3'-甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物7);2-(3'-甲氧基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物8);2-(3'-氯基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物9);及2-(3',5'-二甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物10)。In a specific embodiment of the present invention, the xylose derivative is one selected from the group consisting of: 2- (4'-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 1); 2- (4'-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 2); 2- (4'-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 3); 2- (2'-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 4); 2- (2'-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 5); 2- (2'-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 6); 2- (3'-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 7); 2- (3'-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 8); 2- (3'-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (Compound 9); and 2- (3 ', 5'-dimethylbiphenyl-4-yloxy) tetrahydro- 2H -piran-3,4,5-triol (Compound 10).
在另一方面,本發明提供一種根據本發明合成木醣衍生物之方法。該方法包含以下步驟: 以一保護基保護木醣,接著併入一鹵素原子作為一脫離基; 移去該保護基及使用一水溶性配位體以在水溶液中與鈀觸媒進行鈴木(Suzuki)交叉耦合反應以合成該衍生物。In another aspect, the present invention provides a method for synthesizing a xylose derivative according to the present invention. The method includes the steps of: protecting a xylose with a protecting group, and then incorporating a halogen atom as a leaving group; removing the protecting group and using a water-soluble ligand to perform a palladium catalyst in aqueous solution with Suzuki (Suzuki ) Cross-coupling reaction to synthesize the derivative.
在本發明之一實例中,該鹵素原子為碘原子。In one embodiment of the present invention, the halogen atom is an iodine atom.
在本發明之一實例中,回收該水溶性配位體。In one example of the present invention, the water-soluble ligand is recovered.
在本發明之一實例中,回收該鈀觸媒。In one example of the present invention, the palladium catalyst is recovered.
在本發明之一實例中,該鈀觸媒為PdCl2 (NH3 )2 ,且該水溶性配位體為陽離子2,2'-聯吡啶配位體。In one example of the present invention, the palladium catalyst is PdCl 2 (NH 3 ) 2 , and the water-soluble ligand is a cationic 2,2′-bipyridine ligand.
在本發明之一實例中,陽離子2,2'-聯吡啶配位體溶於水中以形成溶液A;且PdCl2 (NH3 )2 溶於水中以形成溶液B;及將該溶液A添加至溶液B以產生混濁溶液,其最終變清澈以獲得水溶性鈀觸媒。In one example of the present invention, the cationic 2,2'-bipyridine ligand is dissolved in water to form solution A; and PdCl 2 (NH 3 ) 2 is dissolved in water to form solution B; and the solution A is added to Solution B to produce a cloudy solution, which eventually became clear to obtain a water-soluble palladium catalyst.
在本發明之一實例中,該鈴木交叉耦合反應在不高於100°C之溫度下進行。In one embodiment of the present invention, the Suzuki cross-coupling reaction is performed at a temperature not higher than 100 ° C.
除非另外定義,本文所用之所有技術及科學術語具有與熟習本發明所屬領域之技術者普遍了解之相同意義。Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
如本文所用,單數形式「一」(a、an)及「該」包括複數參照,除非另外明確指示內容。因此,例如,對「一樣本」之參照包括複數個此等樣本及熟習本技術者已知之其等同物。As used herein, the singular forms "a" (a, an) and "the" include plural referents unless the content is specifically indicated otherwise. Thus, for example, reference to "the same" includes a plurality of such samples and equivalents thereof known to those skilled in the art.
如本文所用,術語「鹵素原子」係指選自由以下五個化學相關元素組成之週期表中一族之一原子:氟(F)、氯(Cl)、溴(Br)、碘(I)、及砈(At)。As used herein, the term "halogen atom" refers to an atom selected from the group of the Periodic Table consisting of five chemically related elements: fluorine (F), chlorine (Cl), bromine (Br), iodine (I), and砈 (At).
本發明提供一種用於在水相中在水溶性鈀觸媒存在下合成木醣衍生物之方法,其提供一種用於合成木醣衍生物之友善經濟的綠色化學方法。The invention provides a method for synthesizing a xylose derivative in the presence of a water-soluble palladium catalyst in an aqueous phase, and provides a friendly and economical green chemical method for synthesizing a xylose derivative.
涉及本發明之技術及材料說明如下。The technology and materials related to the present invention are described below.
溶劑純化Solvent purification
在氮氣氛下於一蒸餾裝置上,將硫酸鎂添加至蒸餾瓶中之二氯甲烷中且溫度設定在~50 °C。將餾出液收集在含有乾燥分子篩之燒瓶中。On a distillation apparatus under a nitrogen atmosphere, magnesium sulfate was added to dichloromethane in a distillation flask and the temperature was set at ~ 50 ° C. The distillate was collected in a flask containing dry molecular sieves.
不含水與空氣製程Free of water and air
若該反應對水及空氣敏感,則包括反應、萃取、乾燥、濃縮及管柱層析術之所有實驗製程必須在氮條件中空氣不存在下進行。因此,溶劑及化學品在使用前必須不含水及空氣,且液體必須使用注射器及彎針(Teflon)轉移。使用旋轉真空濃縮器及真空馬達濃縮該溶液。If the reaction is sensitive to water and air, all experimental processes including reaction, extraction, drying, concentration, and column chromatography must be performed in the absence of air in nitrogen conditions. Therefore, solvents and chemicals must be free of water and air before use, and liquids must be transferred using a syringe and a needle (Teflon). The solution was concentrated using a rotary vacuum concentrator and a vacuum motor.
反應方案Reaction scheme
根據本發明,在用於合成木醣衍生物之方法中之總反應方案提供如下: According to the present invention, the overall reaction scheme in the method for synthesizing a xylose derivative is provided as follows:
乙醯化反應Acetylation
在本發明之一實例中,乙醯化反應方案提供如下: In one example of the present invention, the acetylation reaction scheme is provided as follows:
將0.75 g木醣(5 mmol)、2.84 mL (30 mmol)乙酸酐、及2.04 g (30 mmol)咪唑在700 mL二氯甲烷中之溶液置於冰浴中30分鐘,接著攪拌12小時。接著藉由添加甲醇及在冰中攪拌30分鐘驟冷該反應。以二氯甲烷稀釋該混合物,使用HCl調整至中性pH值,並以Et2 O萃取。以常用的後處理(work-up)及管柱層析術後得到白色固體狀乙醯化木醣(1.50 g,94%)。A solution of 0.75 g of xylose (5 mmol), 2.84 mL (30 mmol) of acetic anhydride, and 2.04 g (30 mmol) of imidazole in 700 mL of dichloromethane was placed in an ice bath for 30 minutes, followed by stirring for 12 hours. The reaction was then quenched by adding methanol and stirring for 30 minutes on ice. The mixture was diluted with dichloromethane, adjusted to a neutral pH with HCl, and extracted with Et 2 O. Acetylated xylose (1.50 g, 94%) was obtained as a white solid by common work-up and column chromatography.
酚衍生反應Phenol derivative reaction
在本發明之一實例中,酚衍生反應方案提供如下 (Lee等人,CARBOHYDRATE CHEMISTRY . 20(6): 503–506,2001):In one example of the present invention, the phenol-derived reaction scheme is provided as follows (Lee et al., CARBOHYDRATE CHEMISTRY . 20 (6): 503-506, 2001):
在氮氣氛下,將1.59 g (5 mmol)乙醯化木醣、1.29 g (7.5 mmol) 4-溴化酚、0.7 mL (5 mmol)TEA、及0.87 mL (12.5 mmol) 在30 mL之二氯甲烷之溶液中攪拌24小時以將4-溴化酚轉化成4-碘酚。以20 mL之飽和水性NaHCO3(aq) 稀釋該混合物並以Et2 O (30mL ×3)萃取。以常用的後處理及管柱層析術後得到白色固體狀產物(1.29g,54%)。Under a nitrogen atmosphere, mix 1.59 g (5 mmol) of acetylated xylose, 1.29 g (7.5 mmol) of 4-bromophenol, 0.7 mL (5 mmol) of TEA, and 0.87 mL (12.5 mmol) of 30 mL. The solution in methyl chloride was stirred for 24 hours to convert 4-bromophenol to 4-iodophenol. The mixture was diluted with 20 mL of saturated aqueous NaHCO 3 (aq) and extracted with Et 2 O (30 mL × 3). The product was obtained as a white solid (1.29 g, 54%) by common post-treatment and column chromatography.
去乙醯反應Deacetylation reaction
在本發明之一實例中,去乙醯反應方案提供如下 (Will等人,J. Phys CHEM. B , 103:8067,1999):In one example of the present invention, the deacetylation reaction scheme is provided as follows (Will et al., J. Phys CHEM. B , 103: 8067, 1999):
在空氣常壓下,將0.478 g (1 mmol)之起始材料與0.33 g (6 mmol)之甲氧鈉在20 mL之甲醇中之溶液攪拌8小時。藉由添加HCl將該混合物調整至中性pH值,且接著以Et2 O (30 mL ×3)萃取。以常見的後處理及管柱層析術後得到白色固體狀產物(0.32g,91%)。A solution of 0.478 g (1 mmol) of starting material and 0.33 g (6 mmol) of sodium methoxide in 20 mL of methanol was stirred at atmospheric pressure for 8 hours. The mixture was adjusted to a neutral pH by adding HCl, and then extracted with Et 2 O (30 mL × 3). After common post-treatment and column chromatography, a white solid product was obtained (0.32 g, 91%).
陽離子cation 2,2-2,2- 聯吡啶配位體之合成Synthesis of bipyridine ligand
在本發明之具體實施例中,該水溶性配位體為一陽離子2,2-聯吡啶配位體,其可根據以下方案合成 (Xue等人,Carbohydrate Research 344:1646–1653,2009): In a specific embodiment of the present invention, the water-soluble ligand is a cationic 2,2-bipyridine ligand, which can be synthesized according to the following scheme (Xue et al., Carbohydrate Research 344: 1646-1653, 2009):
在本發明中可使用以下配位體: 4,4'-二羧基-2,2'-聯吡啶: 4,4'-二甲氧基羰基-2,2'-聯吡啶; 4,4'-雙(羥甲基)-2,2'-聯吡啶: 4,4'-雙(溴甲基)-2,2'-聯吡啶;或 陽離子2,2'-聯吡啶配位體。The following ligands can be used in the present invention: 4,4'-dicarboxy-2,2'-bipyridine: 4,4'-dimethoxycarbonyl-2,2'-bipyridine; 4,4 ' -Bis (hydroxymethyl) -2,2'-bipyridine: 4,4'-bis (bromomethyl) -2,2'-bipyridine; or a cationic 2,2'-bipyridine ligand.
上述配位體之合成提供如下。Synthesis of the aforementioned ligands is provided below.
(1) 4,4'-(1) 4,4'- 二羧基Dicarboxyl -2,2'--2,2'- 聯吡啶Bipyridine 之合成Synthesis
4,4'-二羧基-2,2'-聯吡啶之合成方案提供如下:The synthesis scheme of 4,4'-dicarboxy-2,2'-bipyridine is provided as follows:
將4,4'-二甲基-2,2'-聯吡啶(5 g)溶於125 mL之H2 SO4 (98%)中。添加K2 Cr2 O7 並將溫度維持在~70-80°C之間。當溶液自黃色變成黑色時,驟冷該反應。在過濾及濃縮後得到黃色固體。將此黃色固體溶於170 mL之HNO3(aq) (50%)中並回流4小時。接著將該溶液稀釋至1L,過濾,並以水及丙酮清洗。在濃縮該溶液後,得到呈白色固體之產物(6.12 g,93%),並使用1 H NMR光譜術鑑別。4,4'-dimethyl-2,2'-bipyridine (5 g) was dissolved in 125 mL of H 2 SO 4 (98%). Add K 2 Cr 2 O 7 and maintain the temperature between ~ 70-80 ° C. When the solution changed from yellow to black, the reaction was quenched. A yellow solid was obtained after filtration and concentration. This yellow solid was dissolved in 170 mL of HNO 3 (aq) (50%) and refluxed for 4 hours. The solution was then diluted to 1 L, filtered, and washed with water and acetone. After concentrating the solution, the product was obtained as a white solid (6.12 g, 93%) and identified using 1 H NMR spectroscopy.
(2) 4,4'-(2) 4,4'- 二甲氧基羰基Dimethoxycarbonyl -2,2'--2,2'- 聯吡啶之合成Synthesis of bipyridine
4,4'-二甲氧基羰基-2,2'-聯吡啶之合成方案提供如下: The synthesis scheme of 4,4'-dimethoxycarbonyl-2,2'-bipyridine is provided as follows:
將4,4'-二羧基-2,2'-聯吡啶(6.12 g)溶於115 mL之MeOH(aq) 及15 mL之H2 SO4(aq) 中。在~90–100 °C下回流該溶液24小時,之後將該反應以300 mL之DDW驟冷。添加NaOH(aq) 直到pH到達~8.0。使用二氯甲烷(2 × 50 mL)萃取該有機層並以MgSO4 乾燥。接著在真空蒸發器中過濾及濃縮以產生固體產物(5.9 g,87%)。使用1 H NMR光譜術鑑別化合物。4,4'-Dicarboxy-2,2'-bipyridine (6.12 g) was dissolved in 115 mL of MeOH (aq) and 15 mL of H 2 SO 4 (aq) . The solution was refluxed at ~ 90–100 ° C for 24 hours, after which the reaction was quenched with 300 mL of DDW. NaOH (aq) was added until the pH reached ~ 8.0. The organic layer was extracted with dichloromethane (2 × 50 mL) and dried over MgSO 4 . It was then filtered and concentrated in a vacuum evaporator to give a solid product (5.9 g, 87%). Compounds were identified using 1 H NMR spectroscopy.
(3) 4,4'-(3) 4,4'- 雙double (( 羥甲基Methylol )-2,2'-) -2,2'- 聯吡啶Bipyridine 之合成Synthesis
4,4'-雙(羥甲基)-2,2'-聯吡啶之合成方案提供如下: The synthesis scheme of 4,4'-bis (hydroxymethyl) -2,2'-bipyridine is provided as follows:
將4,4'-二甲氧基羰基-2,2'-聯吡啶(5.9 g)溶於純EtOH中,將硼氫化鈉(12 g)添加於其中。在~90-100 °C下回流該混合物3小時。在冷卻至室溫後,添加飽和NH4 Cl(aq),接著添加300 mL之DDW。接著使用乙酸乙酯(5 × 250 mL)萃取該溶液,以MgSO4 乾燥,在真空蒸發器中過濾然後濃縮以獲得所需固體(4.46 g,95%)。使用1 H NMR光譜術鑑別該產物。4,4'-dimethoxycarbonyl-2,2'-bipyridine (5.9 g) was dissolved in pure EtOH, and sodium borohydride (12 g) was added thereto. The mixture was refluxed at ~ 90-100 ° C for 3 hours. After cooling to room temperature, saturated NH 4 Cl (aq) was added, followed by 300 mL of DDW. The solution was then extracted with ethyl acetate (5 × 250 mL), dried over MgSO 4 , filtered in a vacuum evaporator and concentrated to obtain the desired solid (4.46 g, 95%). The product was identified using 1 H NMR spectroscopy.
(4) 4,4'-(4) 4,4'- 雙double (( 溴甲基Bromomethyl )-2,2'-) -2,2'- 聯吡啶之合成Synthesis of bipyridine
4,4'-雙(溴甲基)-2,2'-聯吡啶之合成方案提供如下: The synthesis scheme of 4,4'-bis (bromomethyl) -2,2'-bipyridine is provided as follows:
將4,4'-雙(羥甲基)-2,2'-聯吡啶(4.46 g)溶於30 mL之HBr (48%)及10 mL之濃硫酸中。接著在110 °C下回流該溶液6小時。當該溶液由淡黃色變成金色時,移去熱源並添加100 mL之DDW以驟冷該反應。用NaOH(aq)將溶液的pH值調整至7.0,引發粉色化合物之沉澱。經由過濾收集沉澱物,以DDW清洗,在真空下乾燥。以乙酸乙酯(2 × 50 mL)萃取液體部份,以MgSO4 乾燥、過濾,及在真空蒸發器中濃縮。獲得所需產物(4.39 g,88%)並經由1 H NMR光譜術鑑別。4,4'-bis (hydroxymethyl) -2,2'-bipyridine (4.46 g) was dissolved in 30 mL of HBr (48%) and 10 mL of concentrated sulfuric acid. The solution was then refluxed at 110 ° C for 6 hours. When the solution changed from pale yellow to gold, remove the heat source and add 100 mL of DDW to quench the reaction. The pH of the solution was adjusted to 7.0 with NaOH (aq), which caused the precipitation of pink compounds. The precipitate was collected via filtration, washed with DDW, and dried under vacuum. With ethyl acetate (2 × 50 mL) and extracted liquid fraction, dried MgSO 4, filtered, and concentrated in a vacuum evaporator. The desired product (4.39 g, 88%) was obtained and identified via 1 H NMR spectroscopy.
(5)(5) 陽離子cation 2,2'-2,2'- 聯吡啶配位體之合成Synthesis of bipyridine ligand
陽離子2,2'-聯吡啶配位體之合成方案提供如下: The synthetic scheme of the cationic 2,2'-bipyridine ligand is provided as follows:
將4,4'-雙(溴甲基)-2,2'-聯吡啶(0.5 g)溶於二氯甲烷並添加20 mL之三甲胺 (50%)。在室溫下靜置該混合物反應24小時。使用冷凍乾燥器2天以移除所有水,並得到所需產物。4,4'-bis (bromomethyl) -2,2'-bipyridine (0.5 g) was dissolved in dichloromethane and 20 mL of trimethylamine (50%) was added. The mixture was allowed to stand at room temperature for 24 hours to react. A freeze dryer was used for 2 days to remove all water and to obtain the desired product.
水溶性鈀觸媒之製備Preparation of water-soluble palladium catalyst
在本發明之一具體實施例中,鈀觸媒為PdCl2 (NH3 )2 ,其亦稱為Pd(NH3 )2 Cl2 。該水溶性鈀觸媒可根據以下方案製備: In a specific embodiment of the present invention, the palladium catalyst is PdCl 2 (NH 3 ) 2 , which is also referred to as Pd (NH 3 ) 2 Cl 2 . The water-soluble palladium catalyst can be prepared according to the following scheme:
在一圓底燒瓶中將該陽離子2,2'-聯吡啶基配位體(0.2 mmol)溶於5 mL水中以形成溶液A。在不同的圓底燒瓶中將PdCl2 (NH3 )2 (0.2 mmol)溶於10 mL水中以形成溶液B。在超音波振動下將溶液A慢慢添加至溶液B中以產生混濁溶液,其最終會變清澈。最後,使用5 mL水將溶液B完全轉換成溶液A,直到該溶液完全清澈。所得水溶性鈀觸媒具有0.2 mmol/20 mL(即,0.01 mmol/mL)之濃度。稀釋本溶液以製備鈀觸媒水溶液,其濃度為0.001及0.0001 mmol/mL。This cationic 2,2'-bipyridyl ligand (0.2 mmol) was dissolved in 5 mL of water in a round bottom flask to form solution A. PdCl 2 (NH 3 ) 2 (0.2 mmol) was dissolved in 10 mL of water in different round bottom flasks to form solution B. Solution A was slowly added to solution B under ultrasonic vibration to produce a cloudy solution, which eventually became clear. Finally, solution B was completely converted into solution A using 5 mL of water until the solution was completely clear. The obtained water-soluble palladium catalyst had a concentration of 0.2 mmol / 20 mL (ie, 0.01 mmol / mL). This solution was diluted to prepare an aqueous palladium catalyst solution, the concentration of which was 0.001 and 0.0001 mmol / mL.
鈴木交互耦合反應Suzuki interactive coupling reaction
該鈴木交互耦合反應方案提供如下 (Wu等人,Tetrahedron Letters. 47: 9267–9270,2006): The Suzuki interactive coupling reaction scheme is provided as follows (Wu et al., Tetrahedron Letters. 47: 9267-9270, 2006):
將起始材料(1 mmol)、芳基硼酸(1.5 mmol)、K2 CO3 (2 mmol)、及H2 O (2 mL)裝填在配備有磁性攪拌子之可密封管中。在苯乙烯例中,必須添加TBAB (1 mmol)。在添加Pd(NH3 )2 Cl2 /L水溶液後,在空氣下使用Teflon塗布之螺帽密封該管。接著將該反應容器在100°C或不高於100°C下置於油浴中24小時。在將反應混合物冷卻至室溫後,以乙酸乙酯萃取該水溶液,在MgSO4 上乾燥有機相,並在真空下移除該溶劑。矽膠上管柱層析術提供所需產物。The starting material (1 mmol), arylboronic acid (1.5 mmol), K 2 CO 3 (2 mmol), and H 2 O (2 mL) were packed in a sealable tube equipped with a magnetic stir bar. In the case of styrene, TBAB (1 mmol) must be added. After adding Pd (NH 3 ) 2 Cl 2 / L aqueous solution, the tube was sealed in air using a Teflon-coated screw cap. The reaction vessel was then placed in an oil bath at 100 ° C or no higher for 24 hours. After the reaction mixture was cooled to room temperature, the aqueous solution extracted with ethyl acetate, the organic phase was dried over MgSO 4, and the solvent was removed in vacuo. Silica-on-column chromatography provides the desired product.
在本發明之一實例中,該鈴木交叉耦合反應在不高於100°C之溫度下進行。In one embodiment of the present invention, the Suzuki cross-coupling reaction is performed at a temperature not higher than 100 ° C.
回收水溶性鈀觸媒Recovery of water-soluble palladium catalyst
回收水溶性鈀觸媒之方案提供如下 (Wu等人,Tetrahedron Letters. 47: 9267–9270,2006):A scheme for recovering water-soluble palladium catalyst is provided as follows (Wu et al., Tetrahedron Letters. 47: 9267-9270, 2006):
將有起始材料(1 mmol)、4-氯苯基硼酸(1.5 mmol)、K2 CO3 (2 mmol)、及H2 O (2 mL) 裝填在配備有磁性攪拌子之可密封管中。在苯乙烯例中,必須添加TBAB(1 mmol)。在添加Pd(NH3 )2 Cl2 /L水溶液後,在空氣下使用Teflon塗布之螺帽密封該管。接著將反應容器在100 °C下置於油浴中24小時。在將反應混合物冷卻至室溫後,以乙酸乙酯萃取該水溶液,在MgSO4 上乾燥有機相,並在真空下移除該溶劑。使用矽膠管柱層析術得到所需產物。在反應後,在劇烈攪拌下以乙酸乙酯清洗該水性反應混合物三次,且根據先前所述之程序將有機產物與組合有機相分離。接著將4-氯苯基硼酸及K2 CO3 裝填於殘餘水溶液以用於下個反應;在苯乙烯例中,需要針對第一次操作添加TBAB。Fill a sealable tube equipped with a magnetic stir bar with starting material (1 mmol), 4-chlorophenylboronic acid (1.5 mmol), K 2 CO 3 (2 mmol), and H 2 O (2 mL) . In the case of styrene, TBAB (1 mmol) must be added. After adding Pd (NH 3 ) 2 Cl 2 / L aqueous solution, the tube was sealed in air using a Teflon-coated screw cap. The reaction vessel was then placed in an oil bath at 100 ° C for 24 hours. After the reaction mixture was cooled to room temperature, the aqueous solution extracted with ethyl acetate, the organic phase was dried over MgSO 4, and the solvent was removed in vacuo. The desired product was obtained using silica column chromatography. After the reaction, the aqueous reaction mixture was washed three times with ethyl acetate with vigorous stirring, and the organic product was separated from the combined organic phase according to the procedure previously described. Next, 4-chlorophenylboronic acid and K 2 CO 3 were charged in the residual aqueous solution for the next reaction. In the case of styrene, TBAB needs to be added for the first operation.
保護基Protection group
通常用於本技術中之任何保護基可用在本發明中。例如,醯基保護基常用在碳水化合物化學,烷基醚用於醚保護以鑑別分析在縮醛酮保護中之多醣、環縮醛或環縮酮,用於胺基部份之保護基(諸如:N -乙醯基及鄰苯二甲基)及其它保護基。一些常用之保護基列舉如下: (1) 酯: Ac; Bz; Piz; (2) 醚: 苯甲基(Bn);p MBn; All; (3) 縮醛(縮酮): Tr; TES; TBDMS; (4) 胺基: N -Ac; AcCl; THP。Any protecting group commonly used in the technology can be used in the present invention. For example, fluorenyl protecting groups are commonly used in carbohydrate chemistry, and alkyl ethers are used for ether protection to identify and analyze polysaccharides, cyclic acetals, or cyclic ketals in acetal protection, and protecting groups such as : N -ethenyl and phthalate) and other protecting groups. Some commonly used protecting groups are listed below: (1) Ester: Ac; Bz; Piz; (2) Ether: Benzyl (Bn); p MBn; All; (3) acetal (ketal): Tr; TES; TBDMS; (4) Amine: N- Ac; AcCl; THP.
根據本發明,已合成新木醣衍生物,其具有通式I式I, 其中(R)m中之m為1至4之整數;R為CH3 、OCH3 、或一鹵素原子。 在本發明之實例中,木醣衍生物為選自由以下組成之群組中之一者:2-(4'-氯基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物1);2-(4'-甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物2);2-(4'-甲氧基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物3);2-(2'-甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物4);2-(2'-氯基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物5);2-(2'-甲氧基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物6);2-(3'-甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物7);2-(3'-甲氧基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物8);2-(3'-氯基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物9);及2-(3',5'-二甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物10)。According to the present invention, a new xylose derivative having the general formula I Formula I, wherein m in (R) m is an integer from 1 to 4; R is CH 3 , OCH 3 , or a halogen atom. In an example of the present invention, the xylose derivative is one selected from the group consisting of: 2- (4'-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 1); 2- (4'-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 2); 2- (4'-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 3); 2- (2'-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 4); 2- (2'-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 5); 2- (2'-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 6); 2- (3'-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 7); 2- (3'-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 8); 2- (3'-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (Compound 9); and 2- (3 ', 5'-dimethylbiphenyl-4-yloxy) tetrahydro- 2H -piran-3,4,5-triol (Compound 10).
以下實施例進一步說明本發明,其作示範之用而非限制。The following examples further illustrate the present invention, which is intended to be exemplary rather than limiting.
實施例Examples
實施例1 起始材料之製備Example 1 Preparation of starting materials
關於木醣衍生物的合成,如下所示之2-(4-碘苯氧基)四氫-2H -哌喃-3,4,5-三醇用作起始材料: Regarding the synthesis of xylose derivatives, 2- (4-iodophenoxy) tetrahydro-2 H -piperan-3,4,5-triol is used as a starting material as follows:
起始材料之總反應方案提供如下: The overall reaction scheme of the starting materials is provided as follows:
藉由矽膠管柱層析術純化粗產物,並得到呈白色粉末之產物,產量為45.9%。圖1A顯示2-(4-碘苯氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR光譜,其特徵為四氫呋喃及羥基部份中之氫原子之峰值在δ~3.00–5.50 ppm之範圍中。圖1B顯示2-(4-碘苯氧基)四氫-2H -哌喃-3,4,5-三醇之13 C NMR光譜,其中該溶劑峰值出現在δ43.5 ppm且在木醣之C1位置處之該羥基出現在δ2.0 ppm。然而,在δ2.0 ppm處之峰值在圖1A中消失,而非對應於苯環之峰值。因此,確認得到預期之產物。The crude product was purified by silica gel column chromatography and the product was obtained as a white powder with a yield of 45.9%. Figure 1A shows the 1 H NMR spectrum of 2- (4-iodophenoxy) tetrahydro-2 H -piperan-3,4,5-triol, which is characterized by the peaks of hydrogen atoms in the tetrahydrofuran and hydroxyl groups In the range of δ ~ 3.00–5.50 ppm. FIG. 1B shows the 13 C NMR spectrum of 2- (4-iodophenoxy) tetrahydro-2 H -piperan-3,4,5-triol, in which the solvent peak appears at δ 43.5 ppm and at xylose The hydroxyl group at the C1 position appears at δ 2.0 ppm. However, the peak at δ 2.0 ppm disappeared in Figure 1A, rather than the peak corresponding to the benzene ring. Therefore, it was confirmed that the expected product was obtained.
1 H NMR (400 MHz,CD6 SO):δ7.59 (d,J = 8.8 Hz,2H),6.84 (d,J = 8.8Hz,2H)。13 C NMR (50 MHz,CD6 SO):δ160.37,141.89,122.97,104.79,86.72,80.27,76.93,73.24,69.62。針對C11 H13 IO4 計算之質量:336.08。 1 H NMR (400 MHz, CD 6 SO): δ 7.59 (d, J = 8.8 Hz, 2H), 6.84 (d, J = 8.8 Hz, 2H). 13 C NMR (50 MHz, CD 6 SO): δ 160.37, 141.89, 122.97, 104.79, 86.72, 80.27, 76.93, 73.24, 69.62. Mass calculated for C 11 H 13 IO 4 : 336.08.
合成木醣衍生物之製備例Preparation Examples of Synthetic Xylose Derivatives
在實施例1中獲得之起始材料用來經由在水溶液中與鈀觸媒進行鈴木交互耦合反應合成木醣衍生物,其方案提供如下: Ar-B(OH)2 The starting material obtained in Example 1 was used to synthesize a xylose derivative via a Suzuki interactive coupling reaction with a palladium catalyst in an aqueous solution. Ar-B (OH) 2
合成10種木醣衍生物,以下實例提供其純化及特徵。木醣及芳基硼酸(Ar-B(OH)2
)之催化結果提供在表1中。 表1:木醣及芳基硼酸之催化結果。
實施例2Example 2
2-(4'-氯基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物1): 2- (4'-Chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (Compound 1):
藉由矽膠管柱層析術純化粗產物以產出呈白色粉末之純化產物,產量為79.2%。圖2A及2B顯示2-(4'-氯基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR光譜。圖2C及2D顯示2-(4'-氯基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之13 C NMR光譜。在該光譜中,在δ ~3.00–5.50 ppm範圍中之峰值對應於羥基及四氫呋喃部份之氫原子。由於在起始材料中存在碘,即2-(4-碘苯氧基)四氫-2H -哌喃-3,4,5-三醇,氫峰值自δ7.71轉移至7.59 ppm。如圖2A-2D所示,確認獲得所需產物。The crude product was purified by silica gel column chromatography to yield a purified product as a white powder with a yield of 79.2%. 2A and 2B show 1 H NMR spectra of 2- (4′-chlorobiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol. FIGS. 2C and 2D show 2- (4'-chloro-biphenyl-4-yloxy) tetrahydro -2 H - pyran-3,4,5-triol The 13 C NMR spectra. In this spectrum, the peaks in the range of δ to 3.00 to 5.50 ppm correspond to the hydrogen atoms of the hydroxyl and tetrahydrofuran portions. Due to the presence of iodine in the starting material, namely 2- (4-iodophenoxy) tetrahydro- 2H -piperan-3,4,5-triol, the hydrogen peak shifted from δ7.71 to 7.59 ppm. As shown in Figures 2A-2D, it was confirmed that the desired product was obtained.
1 H NMR (200 MHz,CD6 SO):δ7.64 (d,J = 8.8Hz,2H),7.59 (d,J = 8Hz,2H),7.46(d,J = 8.6,2H),7.08 (d,J = 8.8Hz,2H)。13 C NMR (50 MHz,CD6 SO):δ156.89,138.4,132.39,131.55,128.86,127.86,127.52,116.73,100.86,76.3,72.97,69.26,65.61。針對C17 H18 O5 計算之質量:302.12。 1 H NMR (200 MHz, CD 6 SO): δ 7.64 (d, J = 8.8 Hz, 2H), 7.59 (d, J = 8 Hz, 2H), 7.46 (d, J = 8.6, 2H), 7.08 ( d, J = 8.8 Hz, 2H). 13 C NMR (50 MHz, CD 6 SO): δ156.89, 138.4, 132.39, 131.55, 128.86, 127.86, 127.52, 116.73, 100.86, 76.3, 72.97, 69.26, 65.61. Mass calculated for C 17 H 18 O 5 : 302.12.
實施例3Example 3
2-(4'-甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物2): 2- (4'-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 2):
藉由矽膠管柱層析術純化粗產物,並得到呈白色粉末之產物,產量為54.5%。圖3A及3B顯示2-(4'-甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR光譜。圖3C顯示2-(4'-甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之13 C NMR光譜。在該光譜中,在δ~3.00–5.50 ppm範圍內之峰值對應於羥基及四氫呋喃部份之氫原子。由於在起始材料中存在碘,即2-(4-碘苯氧基)四氫-2H -哌喃-3,4,5-三醇,該氫共振自δ7.71轉移至7.55 ppm。如圖3A-3C所示,確認獲得所需產物。The crude product was purified by silica gel column chromatography and the product was obtained as a white powder with a yield of 54.5%. 3A and 3B show 1 H NMR spectra of 2- (4′-methylbiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol. FIG. 3C shows a 13 C NMR spectrum of 2- (4′-methylbiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol. In this spectrum, the peaks in the range of δ to 3.00 to 5.50 ppm correspond to the hydrogen atoms of the hydroxyl group and the tetrahydrofuran portion. Due to the presence of iodine in the starting material, ie 2- (4-iodophenoxy) tetrahydro- 2H -piperan-3,4,5-triol, this hydrogen resonance was transferred from δ7.71 to 7.55 ppm. As shown in Figures 3A-3C, it was confirmed that the desired product was obtained.
1 H NMR (200 MHz,CD6 SO):δ7.55 (d,J = 8.6Hz,2H),7.49 (d,J =8.0Hz,2H),7.23 (d,J =7.8Hz,2H),7.06 (d,J = 8.8Hz,2H),2.32 (s,3H)。13 C NMR (50 MHz,CD6 SO):δ156.45,136.77,135.96,133.79,129.25,127.25,125.99,116.70,101.01,76.37,69.30,65.63,20.53。針對C18 H20 O5 計算之質量:316.13。 1 H NMR (200 MHz, CD 6 SO): δ 7.55 (d, J = 8.6 Hz, 2H), 7.49 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 7.8 Hz, 2H), 7.06 (d, J = 8.8Hz, 2H), 2.32 (s, 3H). 13 C NMR (50 MHz, CD 6 SO): δ156.45, 136.77, 135.96, 133.79, 129.25, 127.25, 125.99, 116.70, 101.01, 76.37, 69.30, 65.63, 20.53. Mass calculated for C 18 H 20 O 5 : 316.13.
實施例4Example 4
2-(4'-甲氧基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物3): 2- (4'-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 3):
藉由矽膠管柱層析術純化粗產物,得到呈白色粉末之產物,產量為78.6%。圖4A及4B分別顯示2-(4'-甲氧基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR及13 C NMR光譜。在該光譜中,在δ~3.00–5.50 ppm範圍內之峰值對應於羥基及四氫呋喃部份之氫原子。由於在起始材料中存在碘,即2-(4-碘苯氧基)四氫-2H -哌喃-3,4,5-三醇,該氫原子之化學轉移自δ7.71轉移至7.54 ppm。如圖4A及4B所示,確認獲得所需產物。The crude product was purified by silica gel column chromatography to obtain the product as a white powder with a yield of 78.6%. Figures 4A and 4B show the 1 H NMR and 13 C NMR spectra of 2- (4'-methoxybiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol, respectively. . In this spectrum, the peaks in the range of δ to 3.00 to 5.50 ppm correspond to the hydrogen atoms of the hydroxyl group and the tetrahydrofuran portion. Due to the presence of iodine in the starting material, namely 2- (4-iodophenoxy) tetrahydro- 2H -piperan-3,4,5-triol, the chemical transfer of this hydrogen atom was transferred from δ7.71 to 7.54 ppm. As shown in Figures 4A and 4B, it was confirmed that the desired product was obtained.
1 H NMR (200 MHz,CD6 SO):δ7.54 (d,J = 4.0Hz,2H),7.47 (d,J = 8Hz,2H),3.69 (s,3H)。13 C NMR (50 MHz,CD6 SO):δ158.59,156.16,133.64,127.25,127.03,116.72,114.23,101.04,76.39,73.03,69.33,65.64,55.10。針對C18 H20 O6 計算之質量:316.13。 1 H NMR (200 MHz, CD 6 SO): δ 7.54 (d, J = 4.0 Hz, 2H), 7.47 (d, J = 8 Hz, 2H), 3.69 (s, 3H). 13 C NMR (50 MHz, CD 6 SO): δ158.59, 156.16, 133.64, 127.25, 127.03, 116.72, 114.23, 101.04, 76.39, 73.03, 69.33, 65.64, 55.10. Mass calculated for C 18 H 20 O 6 : 316.13.
實施例5Example 5
2-(2'-甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物4): 2- (2'-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 4):
藉由矽膠管柱層析術純化粗產物,獲得白色粉末之產物,產量為51.8%。圖5A及5B顯示2-(2'-甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR光譜。圖5C顯示2-(2'-甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之13 C NMR光譜。在該光譜中,在δ~3.00–5.50 ppm範圍內之峰值對應於羥基及四氫呋喃部份之氫原子。由於在起始材料中存在碘,即2-(4-碘苯氧基)四氫-2H -哌喃-3,4,5-三醇,該氫原子之共振自δ7.71轉移至7.25 ppm。如圖5A-5C所示,確認獲得所需產物。The crude product was purified by silica gel column chromatography to obtain a white powder product with a yield of 51.8%. 5A and 5B show 1 H NMR spectra of 2- (2′-methylbiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol. FIG. 5C shows a 13 C NMR spectrum of 2- (2′-methylbiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol. In this spectrum, the peaks in the range of δ to 3.00 to 5.50 ppm correspond to the hydrogen atoms of the hydroxyl group and the tetrahydrofuran portion. Due to the presence of iodine in the starting material, namely 2- (4-iodophenoxy) tetrahydro- 2H -piperan-3,4,5-triol, the resonance of this hydrogen atom was transferred from δ7.71 to 7.25 ppm. As shown in Figures 5A-5C, it was confirmed that the desired product was obtained.
1 H NMR (400 MHz,CD6 SO):δ7.25 (d,J =7.28Hz,3H),7.23 (t,J =7.4Hz,2H),7.16 (d,J =4.48Hz,2H),7.06 (d,J =4.48Hz.2H),2.22(s,3H)。13 C NMR (100 MHz,CD6 SO):δ156.66,141.34,135.36,135.22,130.76,130.44,130.01,127.52,126.38,116.46,101.45,76.95,73.58,69.87,66.20,20.71。針對C18 H20 O5 計算之質量:316.13。 1 H NMR (400 MHz, CD 6 SO): δ 7.25 (d, J = 7.28 Hz, 3H), 7.23 (t, J = 7.4 Hz, 2H), 7.16 (d, J = 4.48 Hz, 2H), 7.06 (d, J = 4.48 Hz. 2H), 2.22 (s, 3H). 13 C NMR (100 MHz, CD 6 SO): δ156.66, 141.34, 135.36, 135.22, 130.76, 130.44, 130.01, 127.52, 126.38, 116.46, 101.45, 76.95, 73.58, 69.87, 66.20, 20.71. Mass calculated for C 18 H 20 O 5 : 316.13.
實施例6Example 6
2-(2'-氯基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物5): 2- (2'-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 5):
藉由矽膠管柱層析術純化粗產物,得到呈白色粉末之產物,產量為59.3%。如圖6A及6B所示,其分別提供2-(2'-氯基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR及13 C NMR光譜。在δ~3.00–5.50 ppm範圍內之該等峰值對應於羥基及四氫呋喃部份之氫原子。由於在起始材料中存在碘,即2-(4-碘苯氧基)四氫-2H -哌喃-3,4,5-三醇,該氫原子之共振自δ7.71轉移至7.39 ppm。如圖6A及6B所示,確認獲得所需產物。The crude product was purified by silica gel column chromatography to obtain the product as a white powder with a yield of 59.3%. 6A and 6B, which are provided 2- (2'-chloro-biphenyl-4-yloxy) tetrahydro - 2H - pyran-3,4,5-triol The 1 H NMR and 13 C NMR spectrum. These peaks in the range of δ ~ 3.00-5.50 ppm correspond to the hydrogen atoms of the hydroxyl and tetrahydrofuran portions. Due to the presence of iodine in the starting material, namely 2- (4-iodophenoxy) tetrahydro- 2H -piperan-3,4,5-triol, the resonance of this hydrogen atom was transferred from δ7.71 to 7.39 ppm. As shown in Figures 6A and 6B, it was confirmed that the desired product was obtained.
1 H NMR (400 MHz,CD6 SO):δ7.53(d,6.8Hz,1H),7.39 (d,J = 4.8Hz,2H),7.37 (d,J =4.4Hz,1H),7.35 (t,6.8Hz,2H),7.08 (d,J = 8.8 MHz,2H)。13 C NMR (100 MHz,CD6 SO):δ156.24,138.87,131.78,130.94,130.85,129.81,129.27,128.34,126.94,115.44,100.37,75.92,72.55,68.85,65.20。針對C17 H17 ClO5 計算之質量:336.13。 1 H NMR (400 MHz, CD 6 SO): δ 7.53 (d, 6.8 Hz, 1H), 7.39 (d, J = 4.8 Hz, 2H), 7.37 (d, J = 4.4 Hz, 1H), 7.35 ( t, 6.8Hz, 2H), 7.08 (d, J = 8.8 MHz, 2H). 13 C NMR (100 MHz, CD 6 SO): δ156.24, 138.87, 131.78, 130.94, 130.85, 129.81, 129.27, 128.34, 126.94, 115.44, 100.37, 75.92, 72.55, 68.85, 65.20. Mass calculated for C 17 H 17 ClO 5 : 336.13.
實施例7Example 7
2-(2'-甲氧基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物6): 2- (2'-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 6):
藉由矽膠管柱層析術純化粗產物,得到呈白色粉末之產物,產量為60.8%。圖7A及7B顯示2-(2'-甲氧基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR光譜。圖7C顯示2-(2'-甲氧基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之13 C NMR光譜。在該光譜中,在δ~3.00–5.50 ppm範圍內之峰值對應於羥基及四氫呋喃部份之氫原子。由於在起始材料中存在碘,即2-(4-碘苯氧基)四氫-2H -哌喃-3,4,5-三醇,該氫原子之共振自δ7.71轉移至7.39 ppm。如圖7A-7C所示,確認獲得所需產物。The crude product was purified by silica gel column chromatography to obtain the product as a white powder with a yield of 60.8%. 7A and 7B show 1 H NMR spectra of 2- (2′-methoxybiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol. FIG. 7C shows a 13 C NMR spectrum of 2- (2′-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol. In this spectrum, the peaks in the range of δ to 3.00 to 5.50 ppm correspond to the hydrogen atoms of the hydroxyl group and the tetrahydrofuran portion. Due to the presence of iodine in the starting material, namely 2- (4-iodophenoxy) tetrahydro- 2H -piperan-3,4,5-triol, the resonance of this hydrogen atom was transferred from δ7.71 to 7.39 ppm. As shown in Figures 7A-7C, it was confirmed that the desired product was obtained.
1 H NMR (400 MHz,CD6 SO):δ7.39 (d,6.84Hz,2H),7.32 (t,5.24Hz,1H),7.25 (d,7.32Hz,1H),7.09 (d,6.16Hz,1H),7.04(d,7.04Hz,1H),7.00(d,5.96Hz,2H)。13 C NMR (100 MHz,CD6 SO):δ159.19,156.34,140.70,133.25,129.35,127.22,118.10,116.18,111.92,111.32,100.46,75.90,72.54,68.83,65.16,54.54。針對C18 H20 O6 計算之質量:332.13。 1 H NMR (400 MHz, CD 6 SO): δ 7.39 (d, 6.84 Hz, 2H), 7.32 (t, 5.24 Hz, 1H), 7.25 (d, 7.32 Hz, 1H), 7.09 (d, 6.16 Hz 1H), 7.04 (d, 7.04 Hz, 1H), 7.00 (d, 5.96 Hz, 2H). 13 C NMR (100 MHz, CD 6 SO): δ159.19, 156.34, 140.70, 133.25, 129.35, 127.22, 118.10, 116.18, 111.92, 111.32, 100.46, 75.90, 72.54, 68.83, 65.16, 54.54. Mass calculated for C 18 H 20 O 6 : 332.13.
實施例8Example 8
2-(3'-甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物7): 2- (3'-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 7):
藉由矽膠管柱層析術純化粗產物,得到呈白色粉末之產物,產量為87.5%。圖8A及8B顯示2-(3'-甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR光譜。圖8C顯示2-(3'-甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之13 C NMR光譜。在該光譜中,在δ~3.00–5.50 ppm範圍內之峰值對應於羥基及四氫呋喃部份之氫原子。由於在起始材料中存在碘,即2-(4-碘苯氧基)四氫-2H -哌喃-3,4,5-三醇,該氫之共振自δ7.71轉移至7.57 ppm。如圖8A-8C所示,確認獲得所需產物。The crude product was purified by silica gel column chromatography to obtain the product as a white powder with a yield of 87.5%. 8A and 8B show 1 H NMR spectra of 2- (3′-methylbiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol. FIG. 8C shows a 13 C NMR spectrum of 2- (3′-methylbiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol. In this spectrum, the peaks in the range of δ to 3.00 to 5.50 ppm correspond to the hydrogen atoms of the hydroxyl group and the tetrahydrofuran portion. Due to the presence of iodine in the starting material, namely 2- (4-iodophenoxy) tetrahydro- 2H -piperan-3,4,5-triol, the resonance of this hydrogen shifted from δ7.71 to 7.57 ppm . As shown in Figures 8A-8C, it was confirmed that the desired product was obtained.
1 H NMR (400 MHz,CD6 SO):δ 7.57 (d,11.6Hz,2H),7.41 (s,1H),7.30 (t,6.4Hz,1H),7.12 (d,8H,1H),7.05 (d,2.8Hz,2H),2.49 (s,3H)。13 C NMR (100 MHz,CD6 SO):δ159.19,139.16,137.39,133.51,128.19,127.8,126.41,122.87,116.20,100.49,75.90,72.55,68.84,65.17,20.56。針對C18 H20 O5 計算之質量:316.12。 1 H NMR (400 MHz, CD 6 SO): δ 7.57 (d, 11.6 Hz, 2H), 7.41 (s, 1H), 7.30 (t, 6.4 Hz, 1H), 7.12 (d, 8H, 1H), 7.05 (d, 2.8 Hz, 2H), 2.49 (s, 3H). 13 C NMR (100 MHz, CD 6 SO): δ159.19, 139.16, 137.39, 133.51, 128.19, 127.8, 126.41, 122.87, 116.20, 100.49, 75.90, 72.55, 68.84, 65.17, 20.56. Mass calculated for C 18 H 20 O 5 : 316.12.
實施例9Example 9
2-(3'-甲氧基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物8): 2- (3'-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 8):
藉由矽膠管柱層析術純化粗產物,得到呈白色粉末之產物,產量為92.0%。圖9A及9B顯示2-(3'-甲氧基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR光譜。圖9C顯示2-(3'-甲氧基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之13 C NMR光譜。在該光譜中,在δ~3.00–5.50 ppm範圍內之峰值對應於羥基及四氫呋喃部份之氫原子。由於在起始材料中存在碘,即2-(4-碘苯氧基)四氫-2H -哌喃-3,4,5-三醇,該氫原子之共振自δ7.71轉移至7.59 ppm。如圖9A-9C所示,確認獲得所需產物。The crude product was purified by silica gel column chromatography to obtain the product as a white powder with a yield of 92.0%. 9A and 9B show 1 H NMR spectra of 2- (3′-methoxybiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol. FIG. 9C shows a 13 C NMR spectrum of 2- (3′-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol. In this spectrum, the peaks in the range of δ to 3.00 to 5.50 ppm correspond to the hydrogen atoms of the hydroxyl group and the tetrahydrofuran portion. Due to the presence of iodine in the starting material, namely 2- (4-iodophenoxy) tetrahydro- 2H -piperan-3,4,5-triol, the resonance of this hydrogen atom was transferred from δ7.71 to 7.59 ppm. As shown in Figures 9A-9C, it was confirmed that the desired product was obtained.
1 H NMR (400 MHz,CD6 SO):δ7.59 (d,J = 3.6Hz,2H),7.34 (t,J = 8.0Hz,1H),7.17 (d,J = 8.8Hz,1H),7.12 (s,1H),7.07 (D,J = 8.8Hz,2H),6.88 (d,J = 8.4,1H),3.75 (s,3H)。13 C NMR (100 MHz,CD6 SO):δ159.18,156.34,140.70,133.25,129.34,127.21,118.09,116.18,111.91,111.30,100.46,75.89,72.53,68.83,65.16,54.54。針對C18 H20 O6 計算之質量:332.13。 1 H NMR (400 MHz, CD 6 SO): δ 7.59 (d, J = 3.6 Hz, 2H), 7.34 (t, J = 8.0 Hz, 1H), 7.17 (d, J = 8.8 Hz, 1H), 7.12 (s, 1H), 7.07 (D, J = 8.8Hz, 2H), 6.88 (d, J = 8.4, 1H), 3.75 (s, 3H). 13 C NMR (100 MHz, CD 6 SO): δ159.18, 156.34, 140.70, 133.25, 129.34, 127.21, 118.09, 116.18, 111.91, 111.30, 100.46, 75.89, 72.53, 68.83, 65.16, 54.54. Mass calculated for C 18 H 20 O 6 : 332.13.
實施例10Example 10
2-(3'-氯基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物9): 2- (3'-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (Compound 9):
藉由矽膠管柱層析術純化粗產物,得到呈白色粉末之產物,產量為77.2%。圖10A及10B顯示2-(3'-氯基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR光譜。圖10C顯示2-(3'-甲氧基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之13 C NMR光譜。在該光譜中,在δ~3.00–5.50 ppm範圍內之峰值對應於羥基及四氫呋喃部份之氫原子。由於在起始材料中存在碘,即2-(4-碘苯氧基)四氫-2H -哌喃-3,4,5-三醇,該氫原子之共振自δ7.71轉移至7.63 ppm。如圖10A-10C所示,確認獲得所需產物。The crude product was purified by silica gel column chromatography to obtain the product as a white powder with a yield of 77.2%. 10A and 10B show 1 H NMR spectra of 2- (3'-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol. FIG. 10C shows a 13 C NMR spectrum of 2- (3′-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol. In this spectrum, the peaks in the range of δ to 3.00 to 5.50 ppm correspond to the hydrogen atoms of the hydroxyl group and the tetrahydrofuran portion. Due to the presence of iodine in the starting material, namely 2- (4-iodophenoxy) tetrahydro- 2H -piperan-3,4,5-triol, the resonance of this hydrogen atom was transferred from δ7.71 to 7.63 ppm. As shown in Figures 10A-10C, it was confirmed that the desired product was obtained.
1 H NMR (400 MHz,CD6 SO):δ7.66 (s,J =8.0Hz,1H),7.63 (d,J = 8.0Hz,2H),7.59 (d,J =9.8Hz,1H),7.45 (t,J = 8.0 Hz 1H),7.35 (d,J =2 Hz,1H),7.10(d,J = 11.6 Hz,2H)。13 C NMR (100 MHz,CD6 SO):δ156.23,138.86,131.77,130.93,130.84,129.80,129.26,128.31,126.92,115.43,110.36,75.91,72.54,68.86,65.19。針對C17 H17 ClO5 計算之質量:336.08。 1 H NMR (400 MHz, CD 6 SO): δ 7.66 (s, J = 8.0 Hz, 1H), 7.63 (d, J = 8.0 Hz, 2H), 7.59 (d, J = 9.8 Hz, 1H), 7.45 (t, J = 8.0 Hz 1H), 7.35 (d, J = 2 Hz, 1H), 7.10 (d, J = 11.6 Hz, 2H). 13 C NMR (100 MHz, CD 6 SO): δ156.23, 138.86, 131.77, 130.93, 130.84, 129.80, 129.26, 128.31, 126.92, 115.43, 110.36, 75.91, 72.54, 68.86, 65.19. Mass calculated for C 17 H 17 ClO 5 : 336.08.
實施例11Example 11
2-(3',5'-二甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇(化合物10): 2- (3 ', 5'-dimethylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 10):
藉由矽膠管柱層析術純化粗產物,得到呈白色粉末之產物,產量為98.0%。如圖11A及11B分別顯示2-(3',5'-二甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR及13 C NMR光譜。在該光譜中,在δ~3.00–5.50 ppm範圍內之峰值對應於羥基及四氫呋喃部份之氫原子。由於在起始材料中存在碘,即2-(4-碘苯氧基)四氫-2H -哌喃-3,4,5-三醇,該氫原子之共振自δ7.71轉移至7.07 ppm。如圖11A及11B所示,確認獲得所需產物。The crude product was purified by silica gel column chromatography to obtain the product as a white powder with a yield of 98.0%. 11A and 11B show the 1 H NMR of 2- (3 ', 5'-dimethylbiphenyl-4-yloxy) tetrahydro-2 H -piran-3,4,5-triol and 13 C NMR spectrum. In this spectrum, the peaks in the range of δ to 3.00 to 5.50 ppm correspond to the hydrogen atoms of the hydroxyl group and the tetrahydrofuran portion. Due to the presence of iodine in the starting material, that is, 2- (4-iodophenoxy) tetrahydro- 2H -piperan-3,4,5-triol, the resonance of this hydrogen atom was transferred from δ7.71 to 7.07 ppm. As shown in FIGS. 11A and 11B, it was confirmed that the desired product was obtained.
1 H NMR (400 MHz,CD6 SO):δ7.56 (d,J = 8.8Hz,2H),7.21 (s,2H),7.07 (d,J = 8.8Hz,2H),6.95 (s,1H),2.32 (s,6H)。13 C NMR (100 MHz,CD6 SO):δ156.12,139.14,137.21,133.62,127.74,127.60,123.60,116.14,110.49,75.89,72.54,68.83,65.17,20.47。針對C19 H22 O5 計算之質量:330.15。 1 H NMR (400 MHz, CD 6 SO): δ 7.56 (d, J = 8.8 Hz, 2H), 7.21 (s, 2H), 7.07 (d, J = 8.8 Hz, 2H), 6.95 (s, 1H ), 2.32 (s, 6H). 13 C NMR (100 MHz, CD 6 SO): δ156.12, 139.14, 137.21, 133.62, 127.74, 127.60, 123.60, 116.14, 110.49, 75.89, 72.54, 68.83, 65.17, 20.47. Mass calculated for C 19 H 22 O 5 : 330.15.
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當結合隨附圖式閱讀時將更加了解前述之發明內容以及以下本發明之實施方式。The foregoing summary of the invention and the following embodiments of the present invention will be better understood when read in conjunction with the accompanying drawings.
在該等圖式中:In these schemes:
圖1A顯示起始材料2-(4-碘苯氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR光譜,其特徵為四氫呋喃與羥部份之氫原子的峰值在δ~3.00–5.50 ppm之範圍中,其中在2.0 ppm之峰值消失,而非對應於苯環之峰值。Figure 1A shows the 1 H NMR spectrum of the starting material 2- (4-iodophenoxy) tetrahydro-2 H -piperan-3,4,5-triol, which is characterized by hydrogen atoms of the tetrahydrofuran and the hydroxyl moiety The peak in the range of δ ~ 3.00–5.50 ppm, where the peak at 2.0 ppm disappears, instead of corresponding to the peak of the benzene ring.
圖1B顯示2-(4-碘苯氧基)四氫-2H -哌喃-3,4,5-三醇之13 C NMR光譜,其特徵為在∂ 43.5 ppm之溶劑峰值且在木醣之C1位置處的羥基出現在δ2.0 ppm。Figure 1B shows the 13 C NMR spectrum of 2- (4-iodophenoxy) tetrahydro-2 H -piperan-3,4,5-triol, which is characterized by a solvent peak at ∂ 43.5 ppm and at xylose The hydroxyl group at the C1 position appears at δ 2.0 ppm.
圖2A顯示2-(4'-氯基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR光譜,其特徵為在δ~3.00–5.50 ppm範圍內之峰值對應於羥基及四氫呋喃部份的氫原子。FIG. 2A shows a 1 H NMR spectrum of 2- (4′-chlorobiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol, which is characterized by δ to 3.00. Peaks in the range of –5.50 ppm correspond to the hydrogen atoms of the hydroxyl and tetrahydrofuran moieties.
圖2B顯示2-(4'-氯基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR光譜的放大圖。FIG. 2B shows an enlarged view of a 1 H NMR spectrum of 2- (4′-chlorobiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol.
圖2C顯示2-(4'-氯基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之13 C NMR光譜。FIG. 2C shows a 13 C NMR spectrum of 2- (4′-chlorobiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol.
圖2D顯示2-(4'-氯基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之13 C NMR光譜之放大圖。FIG. 2D shows an enlarged 13 C NMR spectrum of 2- (4′-chlorobiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol.
圖3A顯示2-(4'-甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR光譜,其特徵為在δ~3.00–5.50 ppm範圍中之峰值對應於羥基及四氫呋喃部份的氫原子。FIG. 3A shows a 1 H NMR spectrum of 2- (4′-methylbiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol, which is characterized by δ to 3.00 The peaks in the –5.50 ppm range correspond to the hydrogen atoms of the hydroxyl and tetrahydrofuran portions.
圖3B顯示2-(4'-甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR光譜的放大圖。FIG. 3B shows an enlarged view of a 1 H NMR spectrum of 2- (4′-methylbiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol.
圖3C顯示2-(4'-甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之13 C NMR光譜。FIG. 3C shows a 13 C NMR spectrum of 2- (4′-methylbiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol.
圖4A顯示2-(4'-甲氧基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR光譜,其特徵為在δ~3.00–5.50 ppm範圍內之峰值對應於羥基及四氫呋喃部份的氫原子。FIG. 4A shows a 1 H NMR spectrum of 2- (4′-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol, which is characterized by δ to 3.00 Peaks in the range of –5.50 ppm correspond to the hydrogen atoms of the hydroxyl and tetrahydrofuran moieties.
圖4B顯示2-(4'-甲氧基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之13 C NMR光譜。FIG. 4B shows a 13 C NMR spectrum of 2- (4′-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol.
圖5A顯示2-(2'-甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR光譜。在δ~3.00-5.50 ppm範圍內之峰值對應於羥基及四氫呋喃部份之氫原子。FIG. 5A shows a 1 H NMR spectrum of 2- (2′-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol. The peak in the range of δ to 3.00-5.50 ppm corresponds to the hydrogen atom of the hydroxyl group and the tetrahydrofuran portion.
圖5B顯示2-(2'-甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR光譜的放大圖。FIG. 5B shows an enlarged view of a 1 H NMR spectrum of 2- (2′-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol.
圖5C顯示2-(2'-甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之13 C NMR光譜。FIG. 5C shows a 13 C NMR spectrum of 2- (2′-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol.
圖6A顯示2-(2'-氯基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR光譜,其特徵為在δ~3.00–5.50 ppm範圍內之峰值對應於羥基及四氫呋喃部份的氫原子。FIG. 6A shows the 1 H NMR spectrum of 2- (2'-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol, which is characterized by δ ~ 3.00– The peaks in the 5.50 ppm range correspond to the hydrogen atoms of the hydroxyl and tetrahydrofuran moieties.
圖6B顯示2-(2'-氯基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之13 C NMR光譜。FIG. 6B shows a 13 C NMR spectrum of 2- (2′-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol.
圖7A顯示2-(2'-甲氧基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR光譜,其特徵為在δ~3.00–5.50 ppm範圍內之峰值對應於羥基及四氫呋喃部份的氫原子。FIG. 7A shows the 1 H NMR spectrum of 2- (2'-methoxybiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol, which is characterized by δ ~ Peaks in the range of 3.00–5.50 ppm correspond to the hydrogen atoms of the hydroxyl and tetrahydrofuran portions.
圖7B顯示2-(2'-甲氧基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR光譜的放大圖。FIG. 7B shows an enlarged view of the 1 H NMR spectrum of 2- (2′-methoxybiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol.
圖7C顯示2-(2'-甲氧基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之13 C NMR光譜。FIG. 7C shows a 13 C NMR spectrum of 2- (2′-methoxybiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol.
圖8A顯示2-(3'-甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR光譜,其特徵為在δ~3.00–5.50 ppm範圍中之峰值對應於羥基及四氫呋喃部份的氫原子。FIG. 8A shows a 1 H NMR spectrum of 2- (3′-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol, which is characterized by δ ~ 3.00– The peaks in the 5.50 ppm range correspond to the hydrogen atoms of the hydroxyl and tetrahydrofuran moieties.
圖8B顯示2-(3'-甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR光譜的放大圖。FIG. 8B shows an enlarged view of the 1 H NMR spectrum of 2- (3′-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol.
圖8C顯示2-(3'-甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之13 C NMR光譜。FIG. 8C shows a 13 C NMR spectrum of 2- (3′-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol.
圖9A顯示2-(3'-甲氧基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR光譜,其特徵為在δ~3.00–5.50 ppm範圍內之峰值對應於羥基及四氫呋喃部份的氫原子。FIG. 9A shows the 1 H NMR spectrum of 2- (3′-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol, which is characterized by δ to 3.00 Peaks in the range of –5.50 ppm correspond to the hydrogen atoms of the hydroxyl and tetrahydrofuran moieties.
圖9B顯示2-(3'-甲氧基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR光譜的放大圖。FIG. 9B shows an enlarged view of the 1 H NMR spectrum of 2- (3′-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol.
圖9C顯示2-(3'-甲氧基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之13 C NMR光譜。FIG. 9C shows a 13 C NMR spectrum of 2- (3′-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol.
圖10A顯示2-(3'-氯基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR光譜,其特徵為在δ~3.00-5.50 ppm範圍內之峰值對應於羥基及四氫呋喃部份的氫原子。FIG. 10A shows a 1 H NMR spectrum of 2- (3′-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol, which is characterized by δ to 3.00- The peaks in the 5.50 ppm range correspond to the hydrogen atoms of the hydroxyl and tetrahydrofuran moieties.
圖10B顯示2-(3'-氯基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR光譜的放大圖。FIG. 10B shows an enlarged view of the 1 H NMR spectrum of 2- (3′-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol.
圖10C顯示2-(3'-甲氧基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之13 C NMR光譜。FIG. 10C shows a 13 C NMR spectrum of 2- (3′-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol.
圖11A顯示2-(3',5'-二甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之1 H NMR光譜,其特徵為在δ~3.00–5.50 ppm範圍內之峰值對應於羥基及四氫呋喃部份的氫原子。FIG. 11A shows a 1 H NMR spectrum of 2- (3 ′, 5′-dimethylbiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol, which is characterized by: The peaks in the range of δ to 3.00–5.50 ppm correspond to the hydrogen atoms of the hydroxyl group and the tetrahydrofuran portion.
圖11B顯示2-(3',5'-二甲基聯苯-4-基氧基)四氫-2H -哌喃-3,4,5-三醇之13 C NMR光譜。FIG. 11B shows a 13 C NMR spectrum of 2- (3 ′, 5′-dimethylbiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol.
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