三氯蔗糖 | 56038-13-2

• 物质功能分类: 生物化工 - 糖类化合物 - 双糖
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 三氯蔗糖
• 中文别名: 1-(1,6-二氯-1,6-双脱氧-β-D-呋喃果糖)-4-氯-4-脱氧-α-D-半乳糖吡喃糖苷；蔗糖素；4,1',6'-三氯-4,1',6'-三脱氧半乳型蔗糖；三氯蔗糖(甜味剂)
• 英文名称: Sucralose
• 英文别名: (2R,3R,4R,5R,6R)-2-[(2R,3S,4S,5S)-2,5-bis(chloromethyl)-3,4-dihydroxyoxolan-2-yl]oxy-5-chloro-6-(hydroxymethyl)oxane-3,4-diol
• CAS: 56038-13-2
• 化学式: C₁₂H₁₉Cl₃O₈
• mdl: MFCD03648615
• 分子量: 397.637
• InChiKey: BAQAVOSOZGMPRM-QBMZZYIRSA-N

物化性质

• 熔点：
  115-1018°C
• 比旋光度：
  D +68.2° (c = 1.1 in ethanol)
• 沸点：
  104-107 C
• 密度：
  1.375 g/cm
• LogP：
  -0.51 at 20℃
• 物理描述：
  White to off-white, practically odourless, crystalline powder.
• 颜色/状态：
  White to off white, crystalline powder
• 味道：
  Intensely sweet taste
• 溶解度：
  In water, 2.27X10+4 mg/L at 25 °C (est)
• 蒸汽压力：
  3.25X10-14 mm Hg at 25 °C (est)
• 旋光度：
  [α]D/20 + 84,0° to + 87,5° calculated on the anhydrous basis (10 % w/v solution)
• 碰撞截面：
  177.2 Ų [M+Na]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  129
• 氢给体数：
  5
• 氢受体数：
  8

ADMET

代谢

在给予八名男性受试者单次口服剂量的(14)C-三氯蔗糖（1mg/kg，100微居里）后，平均14.5%（范围8.9至21.8%）的放射性物质在尿液中排出，78.3%（范围69.4至89.6%）在粪便中排出，在5天内。放射性物质的总回收率平均为92.8%。血浆中放射性物质的浓度在给药后约2小时达到最大。三氯蔗糖的平均滞留时间（MRT）为18.8小时，而血浆放射性物质下降的有效半衰期为13小时。两名志愿者给予较高的口服剂量（10 mg/kg，22.7微居里）后，5天内尿液中排出的放射性物质平均为11.2%（9.6和12.7%），粪便中为85.5%（84.1和86.8%）。放射性物质的总回收率为96.7%。粪便中的放射性标记物质基本未变，为三氯蔗糖。尿液中主要是三氯蔗糖，还有两个更具极性的成分，这两个代谢物仅占给药剂量的2.6%（范围1.5至5.1%的剂量）；两个代谢物都具有三氯蔗糖葡萄糖苷酸结合物的特征。

Following a single oral dose of (14)C-sucralose (1mg/kg, 100 microCi) to eight male subjects, a mean of 14.5% (range 8.9 to 21.8%) of the radioactivity was excreted in urine and 78.3% (range 69.4 to 89.6%) in the feces, within 5 days. The total recovery of radioactivity averaged 92.8%. Plasma concentrations of radioactivity were maximal at about 2 hours after dosing. The mean residence time (MRT) for sucralose was 18.8 hr, while the effective half-life for the decline of plasma radioactivity was 13 hr. Two volunteers given a higher oral dose (10 mg/kg, 22.7 uCi) excreted a mean of 11.2% (9.6 and 12.7%) of the radioactivity in urine, and 85.5% (84.1 and 86.8%) in feces over 5 days. The total recovery of radioactivity was 96.7%. The radiolabelled material present in feces was essentially unchanged sucralose. Sucralose was the principal component in the urine together with two more polar components which accounted for only 2.6% of the administered dose (range 1.5 to 5.1% of dose); both metabolites possessed characteristics of glucuronide conjugates of sucralose.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用概述：在一些报告称在过去24小时内摄入了人工加糖饮料和甜味剂包的哺乳母亲以及在所有给予糖精苏打的女性中，在她们的母乳中发现了糖精。由于糖精在口服摄入后吸收不良，它不太可能进入婴儿的血液或对哺乳婴儿造成立即的负面影响，或者摄入超过可接受日摄入量的糖精。摄入含有低卡路里甜味剂的饮食饮料可能会增加哺乳婴儿呕吐的风险。一些作者指出，母乳中糖精的水平可能超过牛奶的甜味阈值，并影响肠道酶和微生物组。他们建议，由于对哺乳婴儿的影响未知，妇女可能希望限制在哺乳期间摄入非营养性甜味剂。 ◉ 对哺乳婴儿的影响：一项横断面调查评估了美国母亲在婴儿11至15周大时哺乳的饮食史。该调查用于估计妇女摄入的无糖苏打水和果汁饮料的量。根据低卡路里甜味剂暴露，婴儿的体重或z分数没有统计学上的显著差异。然而，每周只接触一次或更少低卡路里甜味剂的婴儿比那些没有接触的婴儿有统计学上显著更高的呕吐风险。更高暴露与呕吐无关。无法评估特定甜味剂的影响。 ◉ 对泌乳和母乳的影响：截至修订日期，没有找到相关的已发布信息。

◉ Summary of Use during Lactation:Sucralose has been found in the breastmilk of some nursing mothers who report consuming artificially sweetened beverages and sweetener packets in the past 24 hours and in all women given a sucralose-sweetened soda. Because sucralose is poorly absorbed after oral ingestion, it is not likely to reach the bloodstream of the infant or cause immediate adverse effects in breastfed infants or have a sucralose intake greater than the acceptable daily intake. Ingestion of diet drinks containing low-calorie sweeteners might increase the risk of vomiting in breastfed infants. Some authors note that the levels of sucralose in milk can exceed the sweetness threshold in milk and affect intestinal enzymes and the microbiome. They suggest that women may wish to limit the consumption of nonnutritive sweeteners while breastfeeding because their effect on the nursing infants are unknown. ◉ Effects in Breastfed Infants:A cross-sectional survey assessed the dietary history of US mothers nursing infants between 11 and 15 weeks of age. The survey was used to estimate the amount of diet soda and fruit drinks consumed by the women. There were no statistically significant differences in infants’ weight or z-scores based on low calorie sweetener exposure. However, infants exposed to low calorie sweetener in milk once or less per week had a statistically significantly higher risk of vomiting than those who were not exposed. Greater exposure was not associated with vomiting. It was not possible to assess the effects of specific sweeteners. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

毒理性

• 相互作用

这项研究调查了硫酸锌（5、25、50毫摩尔）抑制12种化学多样性甜味剂的能力，这些甜味剂的强度都与300毫摩尔的蔗糖相匹配[800毫摩尔的葡萄糖，475毫摩尔的果糖，3.25毫摩尔的阿斯巴甜，3.5毫摩尔的糖精，12毫摩尔的钠环己胺，14毫摩尔的阿斯巴甜钾，1.04摩尔的山梨醇，0.629毫摩尔的蔗糖素，0.375毫摩尔的尼奥贺珀辛二氢查耳酮（NHDC），1.5毫摩尔的甜菊糖苷和0.0163毫摩尔的奇果蛋白]。硫酸锌以浓度依赖性的方式抑制了大多数化合物的甜味，50毫摩尔时达到80%的最大抑制。有趣的是，硫酸锌从未抑制过钠环己胺的甜味。这表明钠环己胺可能触达了一种与其他甜味剂不同的甜味机制，这些甜味剂在所有浓度的硫酸锌下都被一致抑制（除了奇果蛋白）。

/The study/...investigated the ability of zinc sulfate (5, 25, 50 mM) to inhibit the sweetness of 12 chemically diverse sweeteners, which were all intensity matched to 300 mM sucrose [800 mM glucose, 475 mM fructose, 3.25 mM aspartame, 3.5 mM saccharin, 12 mM sodium cyclamate, 14 mM acesulfame-K, 1.04 M sorbitol, 0.629 mM sucralose, 0.375 mM neohesperidin dihydrochalcone (NHDC), 1.5 mM stevioside and 0.0163 mM thaumatin]. Zinc sulfate inhibited the sweetness of most compounds in a concentration dependent manner, peaking with 80% inhibition by 50 mM. Curiously, zinc sulfate never inhibited the sweetness of Na-cyclamate. This suggests that Na-cyclamate may access a sweet taste mechanism that is different from the other sweeteners, which were inhibited uniformly (except thaumatin) at every concentration of zinc sulfate.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中毒物清除。如果患者停止呼吸，开始人工呼吸，最好使用需求阀复苏器、袋阀面罩装置或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果发生呕吐，让患者前倾或置于左侧（如果可能的话，头部向下）以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗帮助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，协助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要，进行治疗……。监测休克，如有必要，进行治疗……。预期癫痫发作，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用0.9%的生理盐水（NS）持续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能够吞咽、有强烈的干呕反射且不流口水，则用温水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 高级治疗：对于失去意识、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿……。对于严重的支气管痉挛，考虑给予β受体激动剂，如沙丁胺醇……。监测心率和必要时治疗心律失常……。开始静脉输注D5W /SRP: "保持开放"，最小流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸钠林格氏液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象……。用地西泮或劳拉西泮治疗癫痫……。使用丙美卡因氢氯化物协助眼部冲洗……。/毒物A和B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在给狗单次静脉注射2毫克/公斤（5.8微居里/公斤）的（14）C-三氯半乳糖苏糖后，放射性物质主要通过尿液快速排出。在给药后的3、6和12小时内，尿液中分别排出了平均剂量的29.3%，63.9%和74.1%，在5天后增加到剂量的80.9%。在24小时后，粪便中排出了平均剂量的10.4%，在5天后增加到11.9%。血浆中的放射性在给药后5分钟达到最大值（第一次采样时，8.46微克当量/毫升）。血浆中的放射性以多指数方式下降；浓度在给药后12小时内迅速下降到平均0.057微克当量/毫升，但此后下降速度较慢，在所有动物给药后120小时（5天）仍可检测到（平均，0.013微克当量/毫升）。考虑到全血和血浆浓度，表明放射性从血细胞中清除的速度比从血浆中慢。

After single intravenous doses of (14)C-trichlorogalactosucrose to dogs at a dose level of 2 mg/kg (5.8 uCi/kg) radioactivity was rapidly excreted mainly in the urine. Urinary excretion accounted for means of 29.3%, 63.9% and 74.1% of the dose during 3, 6 and 12 hours after dosing respectively, increasing to 80.9% of the dose after 5 days. Fecal excretion accounted for a mean of 10.4% dose after 24 hours, increasing to 11.9% dose after 5 days. Plasma radioactivity was maximal at 5 minutes after dosing (the first time of sampling, 8.46 ug equivalents/mL). Radioactivity in plasma declined in a multi-exponential fashion; concentrations decreased rapidly to a mean of 0.057 ug equivalents/ml at 12 hours after dosing but thereafter declined more slowly, and were still detectable in all animals at 120 hours after dosing (mean, 0.013 ug equivalents/ml). Consideration of whole-blood and plasma concentrations indicated that radioactivity was cleared more slowly from blood cells than from plasma.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

(14)C-三氯半乳糖苏糖(1毫克/千克；100微居里> 98%纯度)溶于水后口服给8名正常、健康的男性志愿者，并在给药后长达5天内收集血液、尿液和粪便。总共回收的(14)C放射性活度为92.7%(范围87.8-99.2%)，其中大部分放射性物质78.3%(范围69.4-89.6%)在粪便中，其余14.4%(范围8.8-21.7%)在尿液中。血浆中(14)C活性的浓度在给药后约2小时达到峰值，(14)C的浓度相当于大约250纳克/毫升的三氯半乳糖苏糖。血浆浓度在2到12小时之间迅速下降，然后更缓慢地下降，到72小时时，放射性水平接近或低于准确测定的极限。根据平均驻留时间(MRT)18.8小时计算出的平均“有效半衰期”为13.0小时。

(14)C-trichlorogalactosucrose (1 mg/kg; 100 uCi > 98% pure) was given orally dissolved in water to 8 normal, healthy male volunteers and blood, urine and feces collected for up to 5 days after the dose. The total recovery of (14)C-activity was 92.7% (range 87.8-99.2%) with most of the radioactivity 78.3% (range 69.4-89.6%) in the feces, and the remainder 14.4% (range 8.8-21.7%) in the urine. The plasma concentrations of (14)C-activity reached a peak at about 2 hr after the dose, with levels of (14)C equivalent to approximately 250 ng/mL of trichlorogalactosucrose. The plasma concentrations fell rapidly between 2 and 12 hr followed by a more gradual decrease until 72 hr by which time the levels of radioactivity were near or below the limit of accurate determination. The mean 'effective half-life' calculated on the basis of a mean residence time (MRT) of 18.8 hr gives a value of 13.0 hr.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

三名男性受试者单次口服给予碳-14均匀标记的三氯半乳糖醛酸（剂量为1.11 mg/kg体重，0.3 uCi/kg），在5天内平均有13.5%的放射性物质通过尿液排出，82.1%通过粪便排出。在给药后最初的8小时内收集的呼出气体中未检测到（14）CO2。血液中放射性物质的最大水平出现在2-3小时内，其中两名受试者的放射性物质水平以大约2.5小时半衰期下降。对0-3小时尿液的色谱分析表明，仅存在单一放射性成分。

Three male subjects given a single oral dose (1.11 mg/kg b.w., 0.3 uCi/kg) of trichlorogalactosucrose uniformly labelled with carbon-14 excreted an average of 13.5% of the radioactivity in urine and 82.1% in feces in 5 days. No (14)CO2 was detected in expired air collected during the initial 8 hours after dosing. Maximum levels of radioactivity in the blood occurred within 2-3 hours and in two of the subjects declined with a half-life of approximately 2.5 hours. Chromatographic examination of the 0-3 hours urines indicated the presence of only a single radioactive component.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在非孕兔和孕兔单次口服给予（14）C-三氯半乳糖苏糖的剂量为10 mg/kg后，放射性物质主要通过粪便排出。在给药后的24小时内，非孕兔粪便中平均排出了剂量的16.8%，在48小时时增加到31.8%，在120小时时增加到54.7%。孕兔粪便中放射性物质的排出情况相似，给药后的24、48和120小时内，分别有27.8%、43.0%和65.2%的剂量通过此途径排出。在96-120小时后，非孕兔和孕兔分别有5.3%和4.2%的剂量通过粪便排出，表明5天后放射性物质的排出并未完成，这可能是由于兔子的食粪行为。在24小时内，非孕兔和孕兔分别有8.3%和8.6%的剂量通过尿液排出。在5天的给药后，非孕兔和孕兔分别有22.3%和21.5%的剂量逐渐通过尿液排出。在96-120小时后，兔子的尿液中仍然在排出放射性物质（达到剂量的2.9%）。5天后，从非孕兔和孕兔的尿液和粪便中回收的放射性物质平均总量分别占剂量的80.3%和87.0%。未计算在内的剂量可能仍然有待排出，因为在96-120小时后，总共有高达8.4%的剂量被排出。非孕兔和孕兔之间在单次口服（14）C-三氯半乳糖苏糖的吸收和排出方面没有显著差异。

After single oral doses of (14)C-trichlorogalactosucrose to non-pregnant and pregnant rabbits at a dose level of 10 mg/kg, radioactivity was excreted mainly in the feces. During 24 hours after dosing, a mean of 16.8% of the dose was excreted in the feces of non-pregnant animals, increasing to 31.8% during 48 hours and 54.7% during 120 hours. Excretion of radioactivity in the feces of pregnant rabbits was similar, with means of 27.8%, 43.0% and 65.2% of the dose excreted by this route during 24, 48 and 120 hours after dosing, respectively. Means of 5.3% and 4.2% dose were excreted in the feces of non-pregnant and pregnant rabbits respectively during 96-120 hours after dosing, indicating that excretion of radioactivity was not completed after 5 days, probably because of the coprophagic behavior of rabbits. During 24 hours, means of 8.3% and 8.6% of the dose were excreted in the urine of non-pregnant and pregnant rabbits, respectively. Mean totals of 22.3% (non-pregnant rabbits) and 21.5% (pregnant rabbits) of the dose was gradually excreted in the urine during 5 days after dosing. Radioactivity was still being excreted in the urine of rabbits (up to 2.9% dose) during 96-120 hours after dosing. Mean total recoveries of radioactivity from the urine and feces of non- pregnant and pregnant rabbits after 5 days accounted for 80.3% and 87.0% of the dose respectively. The dose not accounted for was presumably still to be excreted since a total of up to 8.4% of the dose was excreted during 96-120 hours after dosing. There were no notable differences in the absorption and excretion of single oral doses of (14)C-trichlorogalactosucrose between non-pregnant and pregnant rabbits.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S37/39
• 危险类别码：
  R36/37/38
• WGK Germany：
  2,3
• 海关编码：
  2932999099
• 危险品运输编号：
  NONH for all modes of transport
• RTECS号：
  LW5440140
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

三氯蔗糖的生产工艺主要包括以下几个步骤：

1. 原料准备

• 原料：以蔗糖为起始原料。

2. 基本化学转化 (a) 基团迁移法（主要生产路线）

1. 基团保护与乙酰化：

   • 将蔗糖进行三苯甲基化和乙酰化，以屏蔽部分羟基。

2. **脱去保护基并进行氯代、乙酰基迁移等步骤，最终获得目标产物。

(b) 其他方法

• 单酯法：较为传统但收率较低。

3. 关键化学反应

1. 三苯甲基化与乙酰化：

   • 在50℃下将蔗糖溶于N-甲基吗啉中，滴加三苯甲基氯进行保护，然后进一步用乙酸酐处理以形成六氧五乙酰基蔗糖。

2. 脱去保护基：

   • 通过酸性条件下脱除三苯甲基，得到四氧四乙酰基蔗糖。

3. 乙酰基迁移：

   • 在吡啶催化下进行乙酰基转移反应。

4. 氯化步骤：

   • 使用亚硫酰氯在碱性条件下对产物进行选择性的氯代。

5. 脱去乙酰基并提纯三氯蔗糖：

   • 最终通过甲醇处理和活性炭吸附等手段得到纯净的三氯蔗糖。

4. 后处理

• 对最终产品进行干燥、结晶等步骤以提高产品质量与纯度。

这种多步合成过程体现了精细化工产品的复杂性，但同时也展示了化学工程师在选择合适路线和优化工艺条件方面的能力。三氯蔗糖因其甜味强烈、无热量等特点，在食品工业中得到了广泛应用。

反应信息

• 作为反应物：
  描述：

  三氯蔗糖 在 氢氧化钾 作用下， 以 水 为溶剂， 反应 4.0h， 以89%的产率得到1,4:3,6-dianhydro-β-D-fructofuranosyl 4-chloro-4-deoxy-α-D-galactopyranoside
  参考文献：
  名称：

  一种从氯化蔗糖中脱水半乳糖蔗糖衍生物的简便方法

  摘要：

  三种新的脱水蔗糖衍生物：1,4：3,6-二脱水-β-D-果糖呋喃糖基4-氯-4-脱氧-α-D-吡喃半乳糖苷（4），1,4：3,6-二脱水-β-D -果糖呋喃糖基3,6-脱水-4-氯-4-脱氧-α-D-吡喃半乳糖苷（6）和1,6-二氯-1,6-二脱氧-β-D-呋喃呋喃糖基-3,6-脱水4由氯化蔗糖制备-氯-4-脱氧-α-D-吡喃半乳糖苷（8）。这些酸酐的结构通过其（1）H和（13）C NMR光谱，ESIMS和元素分析得到证实。给出了6的晶体结构和4（5）的乙酸盐。1,6-二氯-1,6-二脱氧-β-d-果呋喃呋喃糖基4,6-二氯-4,6-二脱氧-α-D-吡喃半乳糖苷中氯甲基对S（N）2反应的相对反应性为发现以6> 6'> 1'的顺序排列。

  DOI：

  10.1016/j.carres.2004.09.013
• 作为产物：
  描述：

  3,4-di-O-acetyl-1,6-dichloro-1,6-dideoxy-β-D-fructofuranosyl 2,3,6-tri-O-acetyl-4-chloro-4-deoxy-α-D-glucopyranoside 在 甲醇 、 sodium methylate 作用下， 反应 2.0h， 以93%的产率得到三氯蔗糖
  参考文献：
  名称：

  WO2008/96928

  摘要：

  公开号：

文献信息

• [EN] ORAL FORMULATIONS OF PYRROLIDINE DERIVATIVES<br/>[FR] FORMULATIONS ORALES DE DÉRIVÉS DE PYRROLIDINE
  申请人：OBSEVA SA

  公开号：WO2015091365A1

  公开（公告）日：2015-06-25

  The present invention relates to solid oral formulations comprising a compound of formula (3Z,5S)-5-(hydroxymethyl)-1-[(2'-methyl-1,1'-biphenyl-4-yl)carbonyl]pyrrolidin-3-one- O-methyloxime, and/or an active metabolite thereof, and the use of said formulations in the treatment and/or prevention of preterm labor, premature birth, dysmenorrhea and embryo implantation failure due to uterine contractions. The present invention is furthermore related to processes for their preparation.

  本发明涉及固体口服制剂，包括化合物的配方(3Z,5S)-5-(羟甲基)-1-[(2'-甲基-1,1'-联苯基-4-基)羰基]吡咯烷-3-酮-O-甲氧肟，和/或其活性代谢物，并且涉及所述制剂在治疗和/或预防早产、早产、经前痛经和子宫收缩引起的胚胎着床失败中的使用。本发明还涉及其制备方法。
• ACYL-HYDRAZONE AND OXADIAZOLE COMPOUNDS, PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME AND USES THEREOF
  申请人：Universidade Federal de Santa Catarina

  公开号：US20150191445A1

  公开（公告）日：2015-07-09

  The present invention relates to acyl-hydrazone compounds, in particular 3,4,5-trimethoxyphenyl-hydrazide derivatives, as well as the oxadiazole analogs thereof and other similar compounds, and to the pharmaceutical use of the same for the treatment of various diseases associated with cell proliferation, such as leukemias, including acute lymphoblastic leukemia (ALL), tumours and inflammation. Acyl-hydrazones have been obtained having activity similar to that of the compound used as a standard in experiments (colchicine). The greater selectivity of the compounds according to the invention is an important feature, associated with fewer side effects than the pharmaceuticals used at present in clinical treatments. The synthetised acyl-hydrazones, more particularly the compounds 02 and 07, exhibited important antileukemic activity, which suggests 02 and 07 as candidates to pharmaceutical prototypes, or to pharmaceuticals for the treatment of leukemias, in particular acute lymphoblastic leukemia (ALL), tumours and other proliferative diseases, such as inflammation. The action mechanism of the most active compounds was determined by using DNA microarrays and subsequent tests indicated by the chip, besides selectivity studies in healthy human lymphocytes.

  本发明涉及酰基腙化合物，特别是3,4,5-三甲氧基苯基腙衍生物，以及其噁二唑类似物和其他类似化合物，以及它们在治疗与细胞增殖相关的各种疾病，如白血病（包括急性淋巴细胞白血病（ALL））、肿瘤和炎症方面的药用。已获得具有与实验中使用的化合物（秋水仙碱）相似活性的酰基腙。根据本发明的化合物具有更大的选择性，与目前在临床治疗中使用的药物相比，副作用更少是一个重要特征。合成的酰基腙，尤其是化合物02和07，表现出重要的抗白血病活性，这表明02和07可能成为药物原型的候选，或用于治疗白血病，特别是急性淋巴细胞白血病（ALL）、肿瘤和其他增殖性疾病，如炎症的药物。最活性化合物的作用机制是通过使用DNA微阵列确定的，并且通过芯片指示的后续测试，以及对健康人类淋巴细胞的选择性研究。
• [EN] PHENOTHIAZINE DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS DE PHÉNOTHIAZINE ET LEURS UTILISATIONS
  申请人：CAMP4 THERAPEUTICS CORP

  公开号：WO2019195789A1

  公开（公告）日：2019-10-10

  The present invention provides phenothiazine compounds, processes for their preparation, pharmaceutical compositions comprising the compounds, and the use of the compounds or the compositions in the treatment of various diseases or conditions, for example ribosomal disorders and ribosomopathies, e.g. Diamond Blackfan anemia (DBA).

  本发明提供了吩噻嗪化合物，其制备方法，包含该化合物的药物组合物，以及在治疗各种疾病或症状中使用该化合物或组合物，例如核糖体紊乱和核糖体病，例如钻石-布莱克范贫血（DBA）。
• Pharmaceutical compositions of drug-oligomer conjugates and methods of treating diseases therewith
  申请人：——

  公开号：US20030069170A1

  公开（公告）日：2003-04-10

  Pharmaceutical compositions that include a drug-oligomer conjugate, a fatty acid component, and a bile salt component are described. The drug is covalently coupled to an oligomeric moiety. The fatty acid component and the bile salt component are present in a weight-to-weight ratio of between 1:5 and 5:1. Methods of treating diseases in a subject in need of such treatment using such pharmaceutical compositions are also provided, as are methods of providing such pharmaceutical compositions.

  描述了包括药物-寡聚物共轭物、脂肪酸成分和胆盐成分的药物组合物。药物以共价键连接到寡聚物基团上。脂肪酸成分和胆盐成分以1:5至5:1的重量比存在。还提供了利用这种药物组合物治疗需要此类治疗的受试者的方法，以及提供这种药物组合物的方法。
• [EN] ASH1L INHIBITORS AND METHODS OF TREATMENT THEREWITH<br/>[FR] INHIBITEURS DE ASH1L ET MÉTHODES DE TRAITEMENT AU MOYEN DE CEUX-CI
  申请人：UNIV MICHIGAN REGENTS

  公开号：WO2017197240A1

  公开（公告）日：2017-11-16

  Provided herein are small molecule inhibitors of ASH1L activity and small molecules that facilitate ASH1L degradation and methods of use thereof for the treatment of disease, including acute leukemia, solid cancers and other diseases dependent on activity of ASH1L.

  本文提供了ASH1L活性的小分子抑制剂，促进ASH1L降解的小分子以及它们的使用方法，用于治疗疾病，包括急性白血病、实体肿瘤和其他依赖于ASH1L活性的疾病。