安赛蜜 | 33665-90-6

• 物质功能分类: 食品添加剂 - 甜味剂
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机硫酸及其衍生物
• 中文名称: 安赛蜜
• 中文别名: 6-甲基-1,2,3-氧恶嗪-4-(3H)-酮-2,2-二氧化物；6-甲基-1,2,3-氧恶嗪-4-(3H)-酮-2,2-二氧；6-甲基-2,2-二氧代-1,2,3-氧硫氮杂；AK糖；安塞米
• 英文名称: acetosulfam
• 英文别名: acesulfame；acesulfame K；acesulfamic acid；6-methyl-3,4-dihydro-1,2,3-oxathiazin-4-one 2,2-dioxide；6-methyl-2,2-dioxooxathiazin-4-one
• CAS: 33665-90-6
• 化学式: C₄H₅NO₄S
• mdl: MFCD00868126
• 分子量: 163.154
• InChiKey: YGCFIWIQZPHFLU-UHFFFAOYSA-N

物化性质

• 熔点：
  123-123.5°
• 密度：
  1.83
• 物理描述：
  Odourless, white, crystalline powder. Approximately 200 times as sweet as sucrose
• 颜色/状态：
  Needles from benzene or chloroform
• 味道：
  Sugar equivalence value relative to sucrose = 200
• 溶解度：
  In water, 270 g/L at 20 °C
• 蒸汽压力：
  9.03X10-6 mm Hg at 25 °C (est)
• 稳定性/保质期：
  Stable under recommended storage conditions. /Acesulfame K/
• 分解：
  When heated to decomposition emits toxic fumes of /sulfur oxides/. /Acesulfame potassium/
• 解离常数：
  pKa = 2.0

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  80.8
• 氢给体数：
  1
• 氢受体数：
  4

ADMET

代谢

Acesulfame K的代谢在接受了10毫克/千克体重单次口服剂量的老鼠和狗的尿液和粪便中进行了调查，以及在口服了5毫克/千克体重的猪的尿液和胆汁中进行了调查。使用的分析方法（薄层色谱、质谱和同位素稀释）在这些样本中仅检测到了原始物质。通过对上述研究中使用的老鼠尿液提取物进行TLC分离，仅揭示了一个与Acesulfame K相同的峰。在对照组或预先处理了Acesulfame K的动物中没有检测到代谢物。同样，在预先以1% Acesulfame K处理了7天的动物中也没有检测到代谢物。/Acesulfame K/

The metabolism of Acesulfame K was investigated in the urine and feces of rats and dogs which had received single oral doses of 10 mg/kg bw, and in the urine and bile of pigs dosed orally with 5 mg/kg bw. The analytical methods used (thin-layer chromatography, mass spectrometry and isotope dilution) detected only the original substance in these samples. Separation by TLC of urinary extracts from rats used in the above study revealed only one peak which was identical with Acesulfame K. No metabolites were detected in control or Acesulfame K-pretreated animals. Similarly, no metabolites were detected in animals which had been pretreated with 1% Acesulfame K for 7 days. /Acesulfame K/

来源:Hazardous Substances Data Bank (HSDB)

代谢

Acesulfame K 的代谢情况在志愿者单次服用 30 毫克/人后，通过血清和尿液样本进行了研究。在所有样本中只检测到了原始物质。/Acesulfame K/

The metabolism of Acesulfame K was studied in serum and urine from human volunteers following a single dose of 30 mg/individual. Only the original substance was detected in all samples. /Acesulfame K/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别和使用：阿斯巴甜（AS）是一种固体。它被用作食品中的人工甜味剂，也用于化妆品中。人体研究：报告了一项案例研究，其中一名已知对亚硫酸盐和磺胺类药物过敏的个体在超过一定阈值水平时对牛磺酸以及非营养性甜味剂阿斯巴甜钾产生超敏反应，这些化合物通常不与过敏反应相关。体外研究表明，长期摄入阿斯巴甜可能会通过损害apoA-I和HDL的功能和结构来加速动脉粥样硬化和衰老。动物研究：在兔子的初级皮肤刺激性试验中，阿斯巴甜K不刺激。阿斯巴甜K未显示抗原效应，只有用BSA致敏的豚鼠出现过敏性反应。阿斯巴甜K在小鼠和大鼠中未表现出致癌性。在大鼠中进行了多代研究，其中雄性和雌性在连续三代中通过饮食摄入0、0.3%、1.0%和3.0%的阿斯巴甜K，每代包括两个连续的窝。在最高剂量组的F0和F1代以及F0代中剂量组的生长速率略有下降。在致畸性研究中，在外观、食物消耗、母体解剖、器官重量或窝数据方面未观察到不良影响；没有观察到可归因于处理的内脏或骨骼异常。阿斯巴甜K在体内和体外的遗传毒性研究中为阴性，包括在S. typhimurium TA98、TA100、TA15325、TA1537、TA1538的Ames试验中0-100 mg/plate，4-5000 ug/plate以及在E.Coli WP2uvrA中4-5000 ug/plate。生态毒性研究：由于阿斯巴甜在环境中的持久性和广泛存在，它被列为新兴污染物。观察到在紫外线照射后阿斯巴甜在Carassius auratus肝脏中的毒性增加。胚胎毒性试验表明，在鱼类胚胎发育期间，低g/L水平的阿斯巴甜转化产物在尾部分离、心率、孵化率和存活率方面产生了显著的不良影响。

IDENTIFICATION AND USE: Acesulfame (AS) is a solid. It is used as artificial sweetener for food, also used in cosmetics. HUMAN STUDIES: A case study is reported whereby an individual with known sulfite and sulfonamide allergies develops hypersensitivity to taurine above a threshold level as well as to the non-nutritive sweetener acesulfame potassium, compounds that are not normally associated with allergic reactions. In vitro studies suggested that long-term consumption of AS might accelerate atherosclerosis and senescence via impairment of function and structure of apoA-I and HDL. ANIMAL STUDIES: Acesulfame K was non-irritant in a primary dermal irritation test in the rabbit. Acesulfame K showed no antigenic effect and only the guinea pigs sensitized with BSA showed anaphylactic reactions. Acesulfame K was not carcinogenic in mice or rats. A multigeneration study in rats was carried out, in which males and females received Acesulfame K at dietary levels of 0, 0.3, 1.0 and 3.0% for three successive generations, each comprising two consecutive litters. Growth rate was slightly decreased in the top dose group of the F0 and F1 generations, and the mid-dose group of the F0 generation. In the teratogenicity studies, no adverse effects were seen in appearance, food consumption, autopsy of the dams, organ weights, or litter data; no visceral or skeletal abnormalities attributable to the treatment were observed. Acesulfame K was negative in the genotoxicity studies in vivo and in vitro, including Ames tests in S. typhimurium TA98, TA100, TA15325, TA1537, TA1538 at 0-100 mg/plate, 4-5000 ug/plate and in E.Coli WP2uvrA at 4-5000 ug/plate. ECOTOXICITY STUDIES: AS is listed as an emerging contaminant due to its environmental persistence and wide occurrence in the environment. An increased toxicity of AS after UV irradiance was observed in the liver of Carassius auratus exposed to AS and its irradiation products. Embryotoxicity tests showed that AS transformation products at the low g/L level produced significant adverse effects in tail detachment, heart rate, hatching rate and survival rate during fish embryo development.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：研究发现，在过去24小时内报告摄入人工甜味饮料和甜味剂包的哺乳期母亲母乳中发现了不同浓度的阿斯巴甜。甚至一些报告称没有摄入人工甜味剂的母亲的母乳中也有少量阿斯巴甜。然而，摄入量不太可能超过可接受的每日摄入量。摄入含有低热量甜味剂的减肥饮料可能会增加哺乳婴儿呕吐的风险。一些作者建议，由于对哺乳婴儿的影响未知，女性在哺乳期间可能希望限制非营养性甜味剂的使用。 ◉ 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周大时的饮食史。该调查用于估计女性摄入的减肥苏打水和果汁饮料的数量。根据低热量甜味剂暴露情况，婴儿的体重或z得分没有统计学上的显著差异。然而，每周只接触一次或更少低热量甜味剂牛奶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。更高暴露量与呕吐无关。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:Acesulfame has been found in variable concentrations in the breastmilk of nursing mothers who report consuming artificially sweetened beverages and sweetener packets in the past 24 hours. Even some mothers who reported not consuming artificial sweeteners have small amounts of acesulfame in their breastmilk. However, it is not likely to reach an 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 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

重金属的生态毒性在很大程度上取决于它们的形态，这受到具有螯合能力的其他共存物质的影响。在当前研究中，通过比较96小时内藻类细胞的特定生长率μ和脉冲振幅调制（PAM）参数（最大光合系统II光化学效率Fv/Fm、实际光化学效率Yield和非光化学猝灭NPQ）来检查Cd(2+)和Cu(2+)对绿藻Scenedesmus obliquus的毒性影响，同时测量了在人工甜味剂（ASs）存在下藻细胞对金属的生物浓缩。ACES的 presence促进了S。obliquus的生长，促进了Cd(2+)在S中的生物浓缩。obliquus，而SUC的影响不大。同时，Cd(2+)对S的EC50值。obliquus生长从0.42 mg/L增加到1.0 mg/L时的0.54 mg/L和SUC的0.48 mg/L。至于Cu(2+)，EC50值分别增加到1.0 mg/L时的0.17 mg/L和0.15 mg/L。总的来说，这两种ASs减少了金属对藻类的毒性，ACE的效果比SUC好。尽管不如细胞特定生长率敏感，但PAM参数可以揭示金属毒性在亚细胞水平上涉及的机制。这是ASs对重金属生态毒性可能影响的第一个证据。

The ecotoxicity of heavy metals depends much on their speciation, which is influenced by other co-existing substances having chelating capacity. In the present study, the toxic effects of Cd(2+) and Cu(2+) on a green algae Scenedesmus obliquus were examined in the presence of two artificial sweeteners (ASs), acesulfame (ACE) and sucralose (SUC) by comparing the cell specific growth rate mu and pulse-amplitude-modulated (PAM) parameters (maximal photosystem II photochemical efficiency Fv/Fm, actual photochemical efficiency Yield, and non-photochemical quenching NPQ) of the algae over a 96-hr period. Simultaneously, the bioconcentration of the metals by the algal cells in the presence of the ASs was measured. The presence of ACE enhanced the growth of S. obliquus and promoted the bioconcentration of Cd(2+) in S. obliquus, while the impacts of SUC were not significant. Meanwhile, EC50 values of Cd(2+) on the growth of S. obliquus increased from 0.42 mg/L to 0.54 mg/L and 0.48 mg/L with the addition of 1.0 mg/L ACE and SUC, respectively. As for Cu(2+), EC50 values increased from 0.13 mg/L to 0.17 mg/L and 0.15 mg/L with the addition of 1.0 mg/L ACE and SUC, respectively. In summary, the two ASs reduced the toxicity of the metals on the algae, with ACE showing greater effect than SUC. Although not as sensitive as the cell specific growth rate, PAM parameters could disclose the mechanisms involved in metal toxicity at subcellular levels. This study provides the first evidence for the possible impact of ASs on the ecotoxicity of heavy metals.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

瑞士白化病雄性小鼠通过灌胃接触了阿斯巴甜（3.5、35、350 mg/kg 体重）和安赛蜜-K（1.5、15和150 mg/kg 体重）的混合物。从股骨中分离出的骨髓细胞进行了染色体畸变的分析。对结果的统计分析显示，阿斯巴甜与安赛蜜-K联合使用不具有显著的遗传毒性。/安赛蜜-K/

Swiss Albino male mice were exposed to blends of aspartame (3.5, 35, 350 mg/kg bw) and acesulfame-K (1.5, 15 and 150mg/kg bw) by gavage. Bone marrow cells isolated from femora were analyzed for chromosome aberrations. Statistical analysis of the results show that aspartame in combination with acesulfame-K is not significantly genotoxic. /Acesulfame K/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

作者们研究了硫酸锌（5、25、50 mM）抑制12种化学多样性甜味剂的能力，这些甜味剂的甜度都与300 mM蔗糖相匹配[800 mM葡萄糖，475 mM果糖，3.25 mM阿斯巴甜，3.5 mM糖精，12 mM环己氨基磺酸钠，14 mM安赛蜜-K，1.04 M山梨醇，0.629 mM三氯蔗糖，0.375 mM新橙皮苷二氢查耳酮（NHDC），1.5 mM甜菊糖和0.0163 mM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 mM时达到80%的最大抑制。有趣的是，硫酸锌从未抑制过环己氨基磺酸钠的甜味。这表明环己氨基磺酸钠可能触达了一种与其他甜味剂不同的甜味机制，这些甜味剂在每种浓度的硫酸锌下都会被均匀抑制（奇果蛋白除外）。我们假设这组化合物要么作用于一个单一的受体，要么作用于多个受体，而这些受体在每个浓度的硫酸锌下都会被同等程度地抑制。

/The authors/ ... 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. We hypothesize that this set of compounds either accesses a single receptor or multiple receptors that are inhibited equally by zinc sulfate at each concentration.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

/MILK/ 非营养性甜味剂（NNS），包括糖精、苏克拉洛斯、阿斯巴甜和醋磺内酰胺钾，在一般人群中普遍消费，除了糖精外，所有这些都被认为是怀孕和哺乳期间安全使用的。苏克拉洛斯（Splenda）目前占据了NNS市场份额的大部分，并且常常与醋磺内酰胺钾结合用于各种食品和饮料中。迄今为止，糖精是唯一一个在母亲消费后在人乳中发现的NNS，而其他NNS则没有明显的信息。从20名哺乳期志愿者中收集了乳汁样本，无论他们是否习惯性摄入NNS。糖精、苏克拉洛斯和醋磺内酰胺钾出现在65%的参与者乳汁样本中，而阿斯巴甜没有被检测到。这些数据表明，NNS经常被哺乳婴儿摄入，因此需要前瞻性临床研究来确定早期通过乳汁摄入NNS是否可能具有临床意义。/醋磺内酰胺钾/

/MILK/ Nonnutritive sweeteners (NNS), including saccharin, sucralose, aspartame, and acesulfame-potassium, are commonly consumed in the general population, and all except for saccharin are considered safe for use during pregnancy and lactation. Sucralose (Splenda) currently holds the majority of the NNS market share and is often combined with acesulfame-potassium in a wide variety of foods and beverages. To date, saccharin is the only NNS reported to be found in human breast milk after maternal consumption, while there is no apparent information on the other NNS. Breast milk samples were collected from 20 lactating volunteers, irrespective of their habitual NNS intake. Saccharin, sucralose, and acesulfame-potassium were present in 65% of participants' milk samples, whereas aspartame was not detected. These data indicate that NNS are frequently ingested by nursing infants, and thus prospective clinical studies are necessary to determine whether early NNS exposure via breast milk may have clinical implications. /Acesulfame potassium/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

单次口服剂量为10毫克/千克体重的(14)C-Acesulfame K给大鼠和狗后，迅速被吸收。大鼠在给药后0.5小时，狗在给药后1-1.5小时，达到的最高血药浓度分别为0.75±0.2 g/mL和6.56±2.08 g/mL。在大鼠中，82-100%的剂量，在狗中，85-100%的剂量通过尿液排出；在两种动物中，97-100%的总放射性通过粪便排出，总回收率接近100%。连续10天每天口服10毫克/千克的大鼠没有显示出累积的证据。给药后三天，器官和血浆中的浓度在肝脏为0.4 nMol/g，在其他组织中为<0.2 nMol/g。给药后七天，狗在所有检查的组织中的浓度<0.2 nMol/g。/安赛蜜K/

Single oral doses of 10 mg (14)C-Acesulfame K/kg bw given to rats and dogs were rapidly absorbed. Maximum blood levels reached were 0.75 plus or minus 0.2 g/mL in rats, 0.5 hr after dosing, and 6.56 plus or minus 2.08 g/mL in dogs, 1-1.5 hr after dosing. In rats, 82-100% of the dose, and in dogs, 85-100% of the dose was excreted in the urine; in both species, 97-100% of the total radioactivity was excreted in feces, and total recovery approximated 100%. Rats given 10 consecutive daily doses of 10 mg/kg orally did not show evidence of accumulation. Three days after dosing, the concn in the organs and plasma was 0.4 nMol/g in liver, and <0.2 nMol/g in other tissues. Seven days after dosing, the concn in dogs was <0.2 nMol/g in all tissues examined. /Acesulfame K/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在经过7天的预处理，喂食含有3%阿斯巴甜K的饮食后，雄性大鼠通过口服灌胃给予含有250毫克阿斯巴甜K的(14)C-阿斯巴甜K（9.6 x 10^8 dpm）。八小时后，动物被处死并切除肝脏和脾脏；从这些器官中分离出DNA和染色质蛋白。在任何一个DNA样本中都无法检测到放射性。与染色质蛋白相关的一个低活性水平（8-11 dpm/mg蛋白质）被认为是由于未改变的阿斯巴甜K的非共价相互作用。/阿斯巴甜K/

After pretreatment for seven days with a diet containing 3% Acesulfame K, male rats were given a dose of 250 mg Acesulfame K containing (14)C-Acesulfame K (9.6 x 108 dpm) by oral gavage. After eight hours the animals were killed and liver and spleen excised; DNA and chromatin protein was isolated from these organs. No radioactivity could be detected on any DNA sample. A low level of activity (8-11 dpm/mg protein) was associated with chromatin protein and this was claimed to be due to non-covalent interactions of unchanged Acesulfame K. /Acesulfame K/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

单次口服剂量大约为15 mg (14)C-Acesulfame K/kg体重给予雄性和雌性大鼠，这些大鼠之前已经用未标记的Acesulfame K进行了预处理，剂量为300 mg/kg饮食，持续60天。未经预处理的对照组动物也以类似的方式给予(14)C-Acesulfame K。在所有动物中，剂量的95.1-98.2%在尿液中以及笼子清洗中回收，0.95-2.86%在粪便中。总回收率为96.3-99.2%。放射性物质的排泄是迅速的，并显示出双相动力学；24小时内排泄了92.6-96.8%的剂量。 ... 在性别之间以及对照组与用Acesulfame K预处理60天的动物之间，排泄途径或速率没有显著差异。/Acesulfame K/

Single oral doses of approximately 15 mg (14)C-Acesulfame K/kg bw were administered to male and female rats which had been pretreated with unlabeled Acesulfame K at a level of 300 mg/kg diet for 60 days. Control animals without pretreatment were also similarly dosed with (14)C-Acesulfame K. In all animals 95.1-98.2% of the dose was recovered in urine and cage washings and 0.95-2.86% in feces. Total recoveries were 96.3-99.2%. Excretion of radioactivity was rapid and displayed biphasic kinetics; 92.6-96.8% of the dose was excreted in 24 hours. ... No significant differences in route or rate of excretion were observed between sexes nor between controls and animals pretreated with Acesulfame K for 60 days. /Acesulfame K/

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• WGK Germany：
  1
• 海关编码：
  2934999090
• 储存条件：
  室温且干燥

制备方法与用途

甜味剂：安赛蜜

化学名称与特性 安赛蜜是一种白色结晶性粉末，熔点250℃，易溶于水，微溶于乙醇。其甜度约为蔗糖的130倍，呈味性质接近糖精，在高浓度时带有苦味。

主要用途

• 食品行业：可广泛应用于液体、固体饮料、冰淇淋、糕点、果酱类、酱菜类、蜜饯、胶姆糖、餐桌用甜味料等。最大使用量为0.3g/kg。
• 医药领域：亦可用作甜味剂。

化学性质

• 易溶于水，微溶于乙醇。
• 熔点123.5℃。
• 与糖醇、蔗糖等有良好的混合性。

安赛蜜的特点

• 非营养型：不提供热量。
• 强烈甜味：甜度约为蔗糖的130倍，呈味性质与糖精相似。高浓度时带有苦味。
• 稳定：在室温下保持稳定，适用于多种食品。

生产方法

安赛蜜由异氰酸氟磺酰或异氰酸氯磺酰与各种活性亚甲基化合物（如α-未取代酮、β-二酮、β-酮酸和β-酮酯等）加工而成。

适用范围

• 糕点: 甜味剂，最大使用量0.3g/kg。
• 面包: 甜味剂，最大使用量0.3g/kg。
• 八宝粥罐头: 甜味剂，最大使用量0.3g/kg。
• 无糖胶基糖果: 甜味剂，最大使用量4.0g/kg。
• 糖果: 甜味剂，最大使用量2.0g/kg。
• 烘焙/炒制坚果与籽类: 甜味剂，最大使用量3.0g/kg。
• 加工食用菌和藻类: 甜味剂，最大使用量0.3g/kg。
• 盐渍的蔬菜: 甜味剂，最大使用量0.3g/kg。
• 酱渍的蔬菜: 甜味剂，最大使用量0.3g/kg。
• 蜜饯类: 甜味剂，最大使用量0.3g/kg。
• 果酱: 甜味剂，最大使用量0.3g/kg。
• 水果罐头: 甜味剂，最大使用量0.3g/kg。
• 冷冻饮品（食用冰除外）: 甜味剂，最大使用量0.3g/kg。

使用注意事项

安赛蜜作为一种非营养型甜味剂，因其不提供热量而广泛应用于食品和医药领域。在使用时需严格遵守GB2760－90规定的最大使用量，确保食品安全与健康。

反应信息

• 作为反应物：
  描述：

  安赛蜜 在 potassium hydroxide 作用下， 以 甲醇 为溶剂， 以97%的产率得到potassium acesulfame
  参考文献：
  名称：

  一种安赛蜜的制备方法

  摘要：

  本发明涉及一种安赛蜜的制备方法。包括以下步骤：(1)乙酰乙酰氨基‑N‑磺酰甲酯的制备：将氨基磺酸甲酯溶于氯代烃类溶剂中，在强碱性大孔树脂的催化下，与双乙烯酮反应生成中间体乙酰乙酰氨基‑N‑磺酰甲酯；(2)安赛蜜的制备：将乙酰乙酰氨基‑N‑磺酰甲酯在铜吡啶配合物催化剂的作用下发生环合反应，同时通过反应精馏将副产甲醇除去；然后经KOH处理得安赛蜜。与现有生产工工艺相比，在环合过程中使用铜吡啶配合物代替强酸催化剂，显著减少了中间体的聚合副反应发生，提升产品收率。同时避免使用三乙胺和SO3，大大减少了废酸和废水的产生。

  公开号：

  CN112876427B
• 作为产物：
  描述：

  potassium acesulfame 在 盐酸 作用下， 以 水 为溶剂， 生成 安赛蜜
  参考文献：
  名称：

  Polymorphism in acesulfame sweetener: structure–property and stability relationships of bending and brittle crystals

  摘要：

  安赛蜜有两种结晶形式，其中形式 I（针状）在机械应力作用下会出现弯曲。晶体结构解释了它们的机械反应。这是首例具有弯曲现象的脂肪族有机化合物。在环境条件下，形态 I 比形态 II 更加稳定。

  DOI：

  10.1039/c0cc00028k

文献信息

• ACESULFAME POTASSIUM COMPOSITIONS AND PROCESSES FOR PRODUCING SAME
  申请人：CELANESE INTERNATIONAL CORPORATION

  公开号：US20180079735A1

  公开（公告）日：2018-03-22

  A process for producing acesulfame potassium, the process comprising the steps of providing a cyclizing agent composition comprising a cyclizing agent and a solvent and having an initial temperature, cooling the cyclizing agent composition to form a cooled cyclizing agent composition having a cooled temperature less than 35° C., reacting an acetoacetamide salt with the cyclizing agent in the cooled cyclizing agent composition to form a cyclic sulfur trioxide adduct composition comprising cyclic sulfur trioxide adduct; and, forming from the cyclic sulfur trioxide adduct in the cyclic sulfur trioxide adduct composition the finished acesulfame potassium composition comprising non-chlorinated acesulfame potassium and less than 39 wppm 5-chloro-acesulfame potassium. The cooled temperature is at least 2° C. less than the initial temperature.

  生产乙烯磺酸钾的过程，包括以下步骤：提供包含环化剂和溶剂的环化剂组合物，并具有初始温度；将环化剂组合物冷却，形成冷却温度低于35°C的冷却环化剂组合物；在冷却环化剂组合物中将乙酰乙酰胺盐与环化剂反应，形成含有环状三氧化硫加合物的环状三氧化硫加合物组合物；并从环状三氧化硫加合物组合物中形成成品乙烯磺酸钾组合物，其中包括非氯化乙烯磺酸钾和少于39 wppm的5-氯乙烯磺酸钾。冷却温度至少比初始温度低2°C。
• Dicationic ionic liquids as new feeding deterrents
  作者：Damian K. Kaczmarek、Kamil Czerniak、Tomasz Klejdysz

  DOI：10.1007/s11696-018-0495-6

  日期：2018.10

  quaternary bis(ammonium) salts with alkyl-1,X-bis(dimethyldecylammonium) cation and saccharinate, acesulfamate, lactate and pyroglutamate anions were synthesized and characterized by 1H and 13C NMR spectroscopy. Thermal gravimetric and differential scanning calorimetry analyses confirmed that all salts were thermally stable and the majority of them exhibited melting points below 100 °C. The physicochemical

  摘要 在这项研究中，合成了具有烷基-1,X-双（二甲基癸铵）阳离子和糖精、乙酰氨基磺酸、乳酸和焦谷氨酸阴离子的新型季双（铵）盐，并通过 1H 和 13C NMR 光谱对其进行了表征。热重和差示扫描量热分析证实，所有盐都是热稳定的，其中大部分的熔点低于 100 °C。测定了三种具有乳酸阴离子的化合物的物理化学性质（粘度、密度、折射率值和溶解度）。所有测试的盐都具有合适的特性，在实际应用中，将减少最重要的贮藏昆虫造成的损失。大多数合成的离子液体具有与印楝素（一种被称为最活跃的拒食剂）相当或更好的威慑活性。图形概要
• 一种西地那非-安赛蜜盐型及其制备方法和用途
  申请人：孙常全

  公开号：CN110128429A

  公开（公告）日：2019-08-16

  本发明涉及一种西地那非‑安赛蜜盐的晶型及其口腔崩解片处方，该晶型中含有1:1摩尔比例的西地那非和安赛蜜，使用单晶X射线衍射在173K时测得晶胞参数为α＝79.5730(10)°,β＝73.7830(10)°,γ＝88.8810(10)°。该晶型在使用Cu‑Kα辐射以2θ表示的粉末X射线衍射光谱中具有16.02°，24.33°，和26.33°特征峰。较市售西地那非柠檬酸盐而言，西地那非‑安赛蜜盐不存在吸湿性问题且能够快速释放。利用西地那非‑安赛蜜盐可以采用直接压片法制备的西地那非的口腔崩解片或舌下含服片。
• Process for the preparation of
  申请人：Hoechst Aktiengesellschaft

  公开号：US04625024A1

  公开（公告）日：1986-11-25

  6-Methyl-3,4-dihydro-1,2,3-oxathiazin-4-one 2,2-dioxide and its non-toxic salts are prepared by reacting acetoacetamide with an S-O compound of the formula I FSO.sub.2 Y (I) wherein Y.dbd.F, Cl, --OSO.sub.2 F or --OSO.sub.2 Cl, preferably only F, in the presence of bases. The non-toxic salts--especially the potassium salt--are valuable synthetic sweeteners.

  通过将乙酰乙酰胺与具有公式I FSO.sub.2 Y（I）的S-O化合物反应，可以制备6-甲基-3,4-二氢-1,2,3-噁嗪-4-酮2,2-二氧化物及其无毒盐。其中Y为F、Cl、--OSO.sub.2 F或--OSO.sub.2 Cl，最好仅为F，在碱的存在下。这些无毒盐，特别是钾盐，是有价值的合成甜味剂。
• Adapting decarbonylation chemistry for the development of prodrugs capable of <i>in vivo</i> delivery of carbon monoxide utilizing sweeteners as carrier molecules
  作者：Ladie Kimberly De La Cruz、Xiaoxiao Yang、Anna Menshikh、Maya Brewer、Wen Lu、Minjia Wang、Siming Wang、Xingyue Ji、Alyssa Cachuela、Haichun Yang、David Gallo、Chalet Tan、Leo Otterbein、Mark de Caestecker、Binghe Wang

  DOI：10.1039/d1sc02711e

  日期：——

  using CO gas as a therapeutic agent for widespread applications, we are interested in developing CO prodrugs through bioreversible caging of CO in an organic compound. Specifically, we have explored the decarboxylation–decarbonylation chemistry of 1,2-dicarbonyl compounds. Examination and optimization of factors favorable for maximal CO release under physiological conditions led to organic CO prodrugs

  一氧化碳作为内源性信号分子在各种器官损伤动物模型中表现出药理功效。为了解决使用 CO 气体作为广泛应用的治疗剂的困难，我们有兴趣通过将 CO 生物可逆地封闭在有机化合物中来开发 CO 前药。具体来说，我们探索了 1,2-二羰基化合物的脱羧-脱羰化学。对生理条件下有利于最大 CO 释放的因素的检查和优化导致使用无热量甜味剂作为连接到 1,2-二羰基核心的离去基团的有机 CO 前药。连接具有适当特性的离去基团可促进所需的水解-脱羧-脱羰反应序列，从而产生 CO。选择一种这样的 CO 前药来概括 CO 在细胞培养研究中对 LPS 诱导的 TNF-α 产生的抗炎作用。小鼠口服给药可将 COHb 水平升高至各种临床前和临床研究中确定的安全有效水平。此外，其药理功效在小鼠急性肾损伤模型中得到证实。这些研究证明了这些前药与良性载体作为口服活性 CO 疗法的潜力。这是口服活性有机 CO 前药与良性载体的第一个例子，该良性载体是