D-果糖 | 470-23-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: D-果糖
• 中文别名: B-D-呋喃果糖；哌非尼酮；d-呋喃果糖
• 英文名称: D-fructose
• 英文别名: fructose；β-D-fructofuranose；beta-D-fructofuranose；(2R,3S,4S,5R)-2,5-bis(hydroxymethyl)oxolane-2,3,4-triol
• CAS: 470-23-5；53188-23-1
• 化学式: C₆H₁₂O₆
• 分子量: 180.158
• InChiKey: RFSUNEUAIZKAJO-ARQDHWQXSA-N

物化性质

• 沸点：
  440.1±45.0 °C(Predicted)
• 密度：
  1.694±0.06 g/cm3(Predicted)
• 物理描述：
  Solid
• 熔点：
  119-122°C
• 溶解度：
  778 mg/mL at 20 °C

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  110
• 氢给体数：
  5
• 氢受体数：
  6

ADMET

代谢

自由果糖直接被小肠吸收。当果糖以蔗糖的形式摄入时，它被消化（分解）然后以自由果糖的形式被吸收。果糖的吸收发生在粘膜膜上，通过涉及GLUT5和GLUT2运输蛋白的促进运输进行。果糖在肝脏中被果糖激酶（Km=0.5 mM）磷酸化。果糖激酶最初产生果糖1-磷酸，后者被醛缩酶B分解产生三糖二羟基醋酸磷酸（DHAP）和甘油醛。DHAP然后转化为甘油-3-磷酸，刺激三酸甘油酯的生成。几乎所有（45%）摄入的纯果糖在3-6小时内被身体用于能量。如果果糖与葡萄糖一起摄入（通常在自然界中是这样），那么在同一时间框架内有高达66%的果糖被用于能量。大约三分之一（29%）到一半（54%）的摄入果糖转化为葡萄糖。不到1%的果糖似乎直接转化为三酸甘油酯。

Free fructose is absorbed directly by the intestine. When fructose is consumed in the form of sucrose, it is digested (broken down) and then absorbed as free fructose. Fructose absorption occurs on the mucosal membrane via facilitated transport involving GLUT5 and GLUT2 transport proteins. Fructose is phosphorylated in the liver by fructokinase (Km= 0.5 mM). Fructokinase initially produces fructose 1-phosphate, which is split by aldolase B to produce the trioses dihydroxyacetone phosphate (DHAP) and glyceraldehyde. DHAP is then converted to glycerol-3-phophate which stimulates production of triglycerides. Nearly half (45%) of all pure fructose consumed is used up within 3-6 hours by the body for energy. If fructose is consumed with glucose (as it typically is in nature), up to 66% of it is used for energy within the same time frame. Roughly a third (29%) to a half (54%) of all fructose consumed is converted to glucose. Less than 1% of fructose appears to be directly converted to triglycerides.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

果糖与其他糖类不同，它能够导致细胞内ATP（三磷酸腺苷）的耗竭、核苷酸转换以及尿酸的产生。由于果糖在肝脏中迅速被磷酸化（转变为果糖-1-磷酸），导致自由磷酸和ATP迅速下降。ATP的下降刺激了腺苷单磷酸（AMP）脱氨酶，该酶将AMP脱氨生成次黄嘌呤核苷酸（IMP），随后IMP被转化为尿酸。尿酸通常是一种抗氧化剂，但在血浆中没有足够的抗坏血酸（维生素C）存在时，它就会作为促氧化剂。由于许多使用高果糖玉米糖浆增甜的软饮料和食品中不含维生素C，因此产生的尿酸可能导致包括痛风、慢性炎症、高血压、体重增加、脂肪肝疾病和肥胖等多种有害影响。许多研究已经表明，高尿酸血症与多种代谢和心血管疾病有关，包括糖尿病和冠心病。升高的血清尿酸水平也被证明是高血压和肾疾病发生的最可靠的预测因子，以及脂肪肝疾病。果糖诱导的尿酸生成还会导致线粒体氧化应激，刺激脂肪积累，这与过量的热量摄入无关。几项研究表明，氧化应激是血管、肾、肝细胞和暴露于尿酸的脂肪细胞中最早期观察到的现象之一。高果糖摄入也与肝脏ATP更严重的耗竭有关，这可能会损害肝脏的“能量平衡”。高果糖饮料也被证明会导致循环中的胰岛素和瘦素水平降低，以及胃饥饿素水平升高。由于瘦素和胰岛素可以减少食欲，而胃饥饿素可以增加食欲，一些研究者怀疑大量摄入果糖可能会增加体重增加的可能性。

Fructose is distinct from other sugars in its ability to cause intracellular ATP depletion, nucleotide turnover, and the generation of uric acid. Uric acid is generated via fructose due to its rapid phosphorylation (to fructose-1-phosphate) in the liver, leading to a rapid drop in free phosphate and ATP. This drop in ATP leads to the stimulation of adenosine monophosphate (AMP) deaminase which deaminates AMP to produce IMP, which is subsequently converted to uric acid (A15346). Uric acid is normally an anti-oxidant but without sufficient amounts of ascorbic acid (vitamin C) present in the plasma, it functions as a pro-oxidant. Because many soft drinks and foods that are sweetened with high fructose corn syrup do not contain vitamin C, the resulting uric acid can lead to a number of harmful effects, including gout, chronic inflammation, hypertension, increased adiposity, fatty liver disease and obesity (A15346). Many studies have shown that elevated uric acid levels are associated with several metabolic and cardiovascular conditions, including diabetes and coronary artery disease (A15346). Elevated serum uric acid has also been shown to be the most reliable predictor for the development of hypertension and incident renal disease (A15347) as well as fatty liver disease (A15348). Fructose-induced uric acid generation also causes mitochondrial oxidative stress that stimulates fat accumulation independent of excessive caloric intake (A15349). Several studies have demonstrated that oxidative stress is one of the earliest phenomena observed in vascular, renal, liver cells and adipocytes exposed to uric acid (A15347). High fructose consumption is also associated with more severe depletion of liver ATP, which may impair liver "energy balance”. High-fructose beverages have also been shown to lead to lower circulating insulin and leptin levels, and higher ghrelin levels. Since leptin and insulin decrease appetite and ghrelin increases appetite, some researchers suspect that eating large amounts of fructose increases the likelihood of weight gain.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类不具有致癌性（未被国际癌症研究机构IARC列名）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

果糖或高果糖玉米糖浆的急性摄入基本上是无毒的。长期的过量果糖摄入已被证明是痛风、胰岛素抵抗、高血压、肥胖、脂肪肝疾病、LDL胆固醇升高和甘油三酯升高的原因（或间接原因），从而导致代谢综合征。在Wistar大鼠（一种糖尿病的实验室模型）中，与10%葡萄糖喂养相比，10%果糖喂养被发现可以使血液甘油三酯水平增加86%，而相同量的葡萄糖对甘油三酯没有影响。2008年的一项研究发现，摄入果糖或富含果糖的食物与痛风发作有显著的相关风险。人们怀疑软饮料（例如碳酸饮料）和其他加糖饮料中发现的果糖是这种增加发病率的主要原因。

Acute consumption of fructose or high fructose corn syrup is essentially non-toxic. Chronic, excess fructose consumption has been shown to be a cause (or indirect cause) of gout, insulin resistance, hypertension, obesity, fatty liver disease, elevated LDL cholesterol and elevated triglycerides, leading to metabolic syndrome. In Wistar rats, a laboratory model of diabetes, 10% fructose feeding as opposed to 10% glucose feeding was found to increase blood triglyceride levels by 86%, whereas the same amount of glucose had no effect on triglycerides. A 2008 study found a substantial risk of incident gout associated with the consumption of fructose or fructose-rich foods. It is suspected that the fructose found in soft drinks (e.g., carbonated beverages) and other sweetened drinks is the primary reason for this increased incidence.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

摄取

Ingestion

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性数据

每天摄入超过100克纯果糖可能会导致体重每周适度但统计学上显著地增加0.44公斤。每天摄入100克或更多的果糖还会显著提高空腹血清甘油三酯水平。 LD50：15000毫克/千克（静脉注射，兔）

Consuming more than 100 g a day of pure fructose may lead to a modest but statistically significant rise in body weight of 0.44 kg a week. Consuming 100 g or more of fructose a day also significantly increases fasting levels of serum triglycerides. LD50: 15000 mg/kg (intravenous, rabbit)

来源:Toxin and Toxin Target Database (T3DB)

反应信息

• 作为反应物：
  描述：

  D-果糖 在 氢气 作用下， 以 水 为溶剂， 140.0 ℃ 、4.0 MPa 条件下， 反应 4.0h， 生成 甘露醇
  参考文献：
  名称：

  铂催化d-葡萄糖水相加氢制得d-山梨糖醇

  摘要：

  在二氧化硅负载的Pt纳米颗粒上系统地研究了d-葡萄糖水相加氢成d-山梨糖醇的过程，以阐明结构-反应性关系和机理。大Pt颗粒上的d-葡萄糖氢化与其在低配位（电子缺陷）的Pt位置上异构化为d-果糖竞争。前一种方法生产的d-山梨醇对3至17 nm的纳米颗粒不敏感，而较小的颗粒则有利于异构化，两种途径均与气相二氧化硅或中孔SBA-15载体的选择无关。而d -fructose被容易地氢化至d-甘露醇在相同的反应条件下，经历了最小的异构化为d-山梨糖醇，因此，它是d-葡萄糖开环和随后的醛糖构象异构体的直接产物。d -山梨醇生产由低青睐d葡萄糖浓度（<10重量％），高ħ 2点的压力（> 40巴）和低反应温度（<140℃），它抑制了不希望的聚合的副反应。

  DOI：

  10.1021/acscatal.6b02369
• 作为产物：
  描述：

  甘露醇 在 recombinant D-mannitol 2-dehydrohenase (E_.C_. 1.1.1.67) from Pseudomonas fluorescens 、 xylose reductase (E_.C_. 1.1.1.21) from Candida tenuis 、 氧气 、 NADH 、 菲醌 作用下， 生成 D-果糖
  参考文献：
  名称：

  新型过氧化氢形成NAD（P）H氧化酶的化学酶模拟物，可有效再生NAD +和NADP +

  摘要：

  由于操作稳定性，动力学效率或热力学平衡的问题，目前在脱氢酶催化的有机合成中再生NAD +和NADP +的方法在技​​术上还不成熟。我们在这里显示，当使用NADH（12 s -1）或NADPH（1.6 s -1）作为辅酶时，假丝酵母木糖还原酶能以良好的周转频率转换9,10-菲醌，并且对这种醌底物（K m≤13μM）。因为氢醌产物与溶解的分子氧的化学反应以与酶促还原相当的速率再生醌，所以建立了化学酶促过程，其中还原酶，9,10-菲醌（25μM）和分子氧可有效促进NAD（P）H生成NAD（P）+。对苯二酚的氧化反应是通过自由基链反应发生的，该自由基链反应涉及超氧化物作为正在传播的物种，每循环一个9,10-菲醌产生摩尔当量的过氧化氢。使用NAD + -或NADP +D-甘露醇（25 mM）依赖性转化为D-果糖作为模型转化，一次批量转化中获得的9,10-菲醌和辅酶的总周转数分别为1000和≤125。

  DOI：

  10.1002/adsc.200800357
• 作为试剂：
  描述：

  4-碘代苯乙酮 在 copper(I) oxide 、 D-果糖 、 水 、 potassium carbonate 作用下， 反应 3.0h， 以60%的产率得到对羟基苯乙酮
  参考文献：
  名称：

  Cu(I)/蔗糖催化芳烃在水中羟基化：蔗糖的双重作用

  摘要：

  已经开发了一种在纯水中由铜 ( I ) 和蔗糖催化的芳基卤化物的羟基化方案。结合实验和理论技术研究了蔗糖的双重作用、反应途径和羟基化的高选择性。

  DOI：

  10.1039/d0ob01683g

文献信息

• [EN] TARGETED DELIVERY AND PRODRUG DESIGNS FOR PLATINUM-ACRIDINE ANTI-CANCER COMPOUNDS AND METHODS THEREOF<br/>[FR] ADMINISTRATION CIBLÉE ET CONCEPTIONS DE PROMÉDICAMENTS POUR COMPOSÉS ANTICANCÉREUX À BASE DE PLATINE ET D'ACRIDINE ET MÉTHODES ASSOCIÉES
  申请人：WAKE FOREST SCHOOL OF MEDICINE

  公开号：WO2013033430A1

  公开（公告）日：2013-03-07

  Acridine containing cispiaiin compounds have been disclosed that show greater efficacy against cancer than other cisplatin compounds. Methods of delivery of those more effective eisp!aiin compounds to the nucleus in cancer ceils is disclosed using one or more amino acids, one or more sugars, one or more polymeric ethers, C i^aikylene-phenyl-NH-C(0)-R.15, folic acid, av03 iniegriii RGD binding peptide, tamoxifen, endoxifen, epidermal growth factor receptor, antibody conjugates, kinase inhibitors, diazoles, triazol.es, oxazoies, erlotinib, and/or mixtures thereof; wherein R]§ is a peptide.

  含有环丙啶结构的吖啶类化合物已被披露，显示出比其他顺铂类化合物更有效地对抗癌症。使用一种或多种氨基酸、一种或多种糖、一种或多种聚合醚、C i^aikylene-phenyl-NH-C(0)-R.15、叶酸、av03整合RGD结合肽、他莫昔芬、恩多西芬、表皮生长因子受体、抗体结合物、激酶抑制剂、二唑类化合物、三唑类化合物、噁唑类化合物、厄洛替尼和/或它们的混合物将这些更有效的吖啶类化合物传递到癌细胞核中的方法被披露；其中R]§是一个肽。
• Additives and products including oligoesters
  申请人：——

  公开号：US20030199593A1

  公开（公告）日：2003-10-23

  The present invention relates to oligoesters and their use or the creation of additives. Oligoester containing additives and/or oligoesters themselves may be used for formulating pharmaceutical preparations, cosmetics or personal care products such as shampoos and conditioners. These oligoesters are particularly useful for the creation of multi-purpose additives that can impart conditioning, long substantivity and/or UV protection. Individual oligoesters and oligoester mixtures are described.

  本发明涉及寡酯及其用途或添加剂的制备。含有寡酯的添加剂和/或寡酯本身可用于配制药物制剂、化妆品或个人护理产品，如洗发水和护发素。这些寡酯对于制备能够赋予调理、长效性和/或紫外线保护的多功能添加剂特别有用。描述了单独的寡酯和寡酯混合物。
• [EN] PSMA-TARGETING AMANITIN CONJUGATES<br/>[FR] CONJUGUÉS D'AMANITINE CIBLANT LE PSMA
  申请人：HEIDELBERG PHARMA RES GMBH

  公开号：WO2019057964A1

  公开（公告）日：2019-03-28

  The invention relates to a PSMA-targeting conjugate comprising (a) an amatoxin; (b) a small molecule PSMA-targeting moiety; and (c) optionally a linker linking said amatoxin and said small molecule PSMA-targeting moiety. The invention furthermore relates to a pharmaceutical composition comprising such conjugate.

  这项发明涉及一种PSMA靶向共轭物，包括(a)阿马毒素；(b)小分子PSMA靶向基团；以及(c)可选地连接所述阿马毒素和所述小分子PSMA靶向基团的连接剂。此外，该发明还涉及包含这种共轭物的药物组合物。
• [EN] 3,5-DIAMINO-6-CHLORO-N-(N-(4-PHENYLBUTYL)CARBAMIMIDOYL) PYRAZINE-2- CARBOXAMIDE COMPOUNDS<br/>[FR] COMPOSÉS 3,5-DIAMINO -6-CHLORO-N-(N- (4-PHÉNYLBUTYL)CARBAMIMIDOYL) PYRAZINE-2-CARBOXAMIDE
  申请人：PARION SCIENCES INC

  公开号：WO2014099673A1

  公开（公告）日：2014-06-26

  The present invention relates compounds of the formula: or pharmaceutically acceptable salts thereof, useful as sodium channel blockers, as well as compositions containing the same, processes for the preparation of the same, and therapeutic methods of use therefore in promoting hydration of mucosal surfaces and the treatment of diseases including cystic fibrosis, chronic obstructive pulmonary disease, asthma, bronchiectasis, acute and chronic bronchitis, emphysema, and pneumonia.

  本发明涉及以下化合物的公式：或其药学上可接受的盐，用作钠通道阻滞剂，以及含有这些化合物的组合物，制备这些化合物的方法，以及在促进粘膜表面水合和治疗包括囊性纤维化、慢性阻塞性肺病、哮喘、支气管扩张、急性和慢性支气管炎、肺气肿和肺炎等疾病的治疗方法。
• CHLORO-PYRAZINE CARBOXAMIDE DERIVATIVES WITH EPITHELIAL SODIUM CHANNEL BLOCKING ACTIVITY
  申请人：Parion Sciences, Inc.

  公开号：US20140171447A1

  公开（公告）日：2014-06-19

  This invention provides compounds of the formula I: and their pharmaceutically acceptable salts, useful as sodium channel blockers, compositions containing the same, therapeutic methods and uses for the same and processes for preparing the same.

  这项发明提供了式I的化合物及其药用盐，可用作钠通道阻滞剂，包含这些化合物的组合物，以及用于这些化合物的治疗方法和用途，以及制备这些化合物的方法。