L-天门冬酰-N-(2,2,4,4-四甲基-3-硫杂环丁基)-D-丙氨酰胺 | 80863-62-3

• 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 - 羧酸及其衍生物
• 中文名称: L-天门冬酰-N-(2,2,4,4-四甲基-3-硫杂环丁基)-D-丙氨酰胺
• 中文别名: 阿力甜；L-Α-天冬氨酰-D-丙氨酰胺
• 英文名称: alitame
• 英文别名: 3-(L-Aspartyl-D-alaninamido)-2,2,4,4-tetramethylthietane；(3S)-3-azaniumyl-4-oxo-4-[[(2R)-1-oxo-1-[(2,2,4,4-tetramethylthietan-3-yl)amino]propan-2-yl]amino]butanoate
• CAS: 80863-62-3
• 化学式: C₁₄H₂₅N₃O₄S
• 分子量: 331.436
• InChiKey: IVBOUFAWPCPFTQ-SFYZADRCSA-N

物化性质

• 熔点：
  136-147°
• 比旋光度：
  D25 +40 to +50° (c = 1 in water)
• 沸点：
  608.5±55.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)
• 溶解度：
  少许溶于甲醇
• LogP：
  1.508 (est)
• 颜色/状态：
  Crystalline powder
• 味道：
  Intensely sweet
• 稳定性/保质期：

  Alitame is stable in dry, room temperature conditions but undergoes degradation at elevated temperatures or when in solution at low pH. Alitame can degrade in a one-stage process to aspartic acid and alanine amide (under harsh conditions) or in a slow two-stage process by first degrading to its beta-aspartic isomer and then to aspartic acid and alanine amide.

计算性质

• 辛醇/水分配系数(LogP)：
  -2.6
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  147
• 氢给体数：
  4
• 氢受体数：
  6

ADMET

代谢

四名男性受试者口服了14C-阿利泰莫（50 mCi; 1 mg/kg bw）。在48小时内不同时间采集了血液样本。在8小时内不同时间测量了呼出的14CO2。尿液和粪便在5天内收集。血浆放射性水平在8到18小时之间达到峰值，并在前48小时内迅速下降，表明吸收缓慢但广泛，随后迅速排泄。呼出的14CO2没有显著增加。尿液放射性在12到24小时之间达到最大，大约有50%的放射性在前24小时内排泄，90%在5天内。三名受试者的粪便排泄占总剂量的7-10%，第四名受试者为2%。主要的尿代谢物是丙氨酸四甲基噻烷酰胺亚砜和丙氨酸四甲基噻烷酰胺葡萄糖苷酸。次要代谢物是丙氨酸四甲基噻烷酰胺和丙氨酸四甲基噻烷酰胺砜。葡萄糖苷酸是前24小时内的主要尿代谢物，而亚砜是在24-48小时期间的主要代谢物。未改变的阿利泰莫少于总尿放射性的1%。在粪便中，所有的放射性都由未改变的阿利泰莫和丙氨酸四甲基噻烷酰胺组成。在血浆中，大部分放射性（80%）由丙氨酸四甲基噻烷酰胺及其葡萄糖苷酸组成。与大鼠和狗不同，人体内的主要尿代谢物是丙氨酸四甲基噻烷酰胺的葡萄糖苷酸。

Four male subjects were administered an oral dose of 14C-alitame (50 mCi; 1 mg/kg bw). Blood samples were taken at various times up to 48 hr. Exhaled 14CO2 was measured at various times up to 8 hr. Urine and faeces were collected over 5 days. Plasma radioactivity levels peaked between 8 and 18 hr and decreased rapidly within the first 48 hr, indicating slow but extensive absorption followed by rapid excretion. There was no significant increase in exhaled 14CO2 above zero. Urinary radioactivity was maximal between 12 and 24 hr with approximately 50% of radioactivity excreted in the first 24 hr and 90% within 5 days Fecal elimination accounted for 7-10% of the total dose in 3 subjects and 2% in the 4th subject. The major urinary metabolites were alanine tetramethylthietane amide sulfoxide and alanine tetramethyl- thietane amide glucuronide. Minor metabolites were alanine tetramethylthietane amide and alanine tetramethylthietane amide sulfone. The glucuronide was the major urinary metabolite in the first 24 hr whereas the sulfoxide was the major metabolite in the 24-48 hr period. Unchanged alitame constituted less than 1% of the total urinary radioactivity. In feces, all of the radioactivity consisted of unchanged alitame and alanine tetramethylthietane amide. In plasma, the major part of the radioactivity (80%) consisted of alanine tetramethylthietane amide and its glucuronide. In contrast to rats and dogs, the major urinary metabolite in humans was found to be the glucuronide of alanine tetramethylthietane amide.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在单次口服剂量为50 mg/kg体重14C-alitame或含3000 mg/kg 14C-alitame的饮食后，在小鼠体内确定的代谢物包括D-丙氨酸四甲基噻烷酰胺亚砜（64.3%）、D-丙氨酸四甲基噻烷酰胺（24.7%）和未改变的阿丽甜（0.9%）。其余代谢物（10.1%）未确定。粪便中的放射性物质确定为39.5%未改变的阿丽甜，51.5% D-丙氨酸四甲基噻烷酰胺，4.6%未确定。

Following a single oral dose of 50 mg/kg bw 14C-alitame or a diet containing 3000 mg/kg 14C-alitame, metabolites identified /in mice/ were D-alanine tetramethylthietane amide sulfoxide (64.3%), D-alanine tetramethylthietane amide (24.7%), and unchanged alitame (0.9%). The remainder metabolites (10.1%) were not identified. Fecal radioactivity was identified as 39.5% unchanged alitame, 51.5% D-alanine tetramethyltbietane amide and 4.6% was not identified.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在一项研究中，为了检查血浆中的代谢物，一组长埃文斯大鼠单次口服剂量为50毫克/千克体重的14C-阿丽甜。对两只大鼠进行连续采血，以确定放射性随时间的变化，另外3只雄性和3只雌性大鼠在6小时时被处死，并通过高效液相色谱法测定了血浆中的放射性。血浆中放射性最高水平出现在给药后4至6小时。主要的代谢物是丙氨酸四甲基噻烷酰胺亚砜（占总放射性的70%），包括自由和乙酰化形式，而未改变的阿丽甜仅占总放射性的1%。

In a study to examine metabolites in plasma, a group of Long-Evans rats received a single oral dose of 50 mg/kg bw 14C-alitame. Two rats were bled serially to determine the time course of radioactivity and a further 3 male and 3 female rats were killed at 6 hr and the plasma radioactivity was assayed by HPLC. Maximum plasma levels occurred at 4 to 6 hr after administration. The major metabolite was alanine tetramethylthietane amide sulfoxide (70% of the total radioactivity), in both the free and acetylated forms with unchanged alitame only 1% of the total radioactivity.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在一项研究中，为了检测尿液中的代谢物，给4只雄性和4只雌性长埃文斯大鼠口服单一剂量的14C-阿斯巴甜，剂量为5毫克/千克体重。在24小时内收集尿液和粪便，并通过高效液相色谱法进行分析。主要的尿液代谢物是丙氨酸四甲基亚砜酰胺（占75-80%），包括自由型和乙酰化型，而未改变的阿斯巴甜仅占总放射活性的1%。

In a study to examine metabolites in urine, 4 male and 4 female Long-Evans rats were administered a single oral dose of 5 mg/kg bw 14C-alitame. Urine and feces were collected over a 24-hour period and analyzed by HPLC. The major urinary metabolite was alanine tetramethylthietane amide sulfoxide (75-80%), in both free and acetylated forms, with unchanged alitame only 1% of the total radioactivity.

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和。如果患者停止呼吸，请开始人工呼吸，最好使用需求阀复苏器、球囊阀面罩设备或口袋面罩，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。如果患者呕吐，让患者向前倾或将其置于左侧（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。寻求医疗救助。 /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，辅助通气。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……。预防癫痫发作，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：对于无意识、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"，最低流量/。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……。使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)

毒理性

• 人类毒性摘录

/人体暴露研究/在一项针对糖尿病患者的90天双盲耐受性研究中，对一组男性受试者和一组女性受试者进行了研究，他们患有I型或II型糖尿病（75人接受治疗，80人作为对照），分别给予胶囊内的阿丽甜，分三次随餐服用，剂量为每天10毫克/千克体重，持续90天，或以同样的方式给予安慰剂。选择这个剂量是因为它比如果饮食中的所有蔗糖都被阿丽甜替代的估计每日摄入量高出十倍。纳入研究的受试者符合以下标准：I型和II型糖尿病患者，无论性别，年龄在15至70岁之间，糖尿病治疗稳定；空腹血糖<250毫克/分升；未使用研究性药物；在过去6个月内未发生心肌梗死；并且无高血压或高血压已得到控制。...在研究期结束时，16名接受治疗的受试者和9名对照受试者退出了项目，其中5名接受治疗的受试者和2名对照受试者因疾病退出。没有受试者因阿丽甜治疗相关的副作用或实验室参数异常而退出。29%的治疗受试者和25%的对照受试者观察到副作用。胃肠道不适是最常见的副作用。特定副作用的发病率和严重程度在两组之间相对均匀分布。在对照或治疗组中，糖尿病控制、临床化学、血液学或尿液参数均未观察到显著变化。从体格检查、血压和脉搏率、体温、体重或心电图记录中未发现与治疗相关的影响。阿丽甜以每天10毫克/千克体重的剂量连续服用90天，对继续研究的I型和II型糖尿病患者来说是良好耐受的。在这个剂量水平上，阿丽甜对这些糖尿病患者控制血清葡萄糖水平的能力没有影响。

/HUMAN EXPOSURE STUDIES/ In a 90-day double-blind tolerance study in diabetic subjects, groups of male and female subjects having either type I or type II diabetes (75 treated, 80 control) were administered either alitame in capsules divided over three meals at dose level of 10 mg/kg bw/day for 90 days, or placebo in the same manner. This dose was chosen because it is ten times greater than the estimated daily intake if all sucrose in the diet were replaced with alitame. Subjects were included on the following criteria: diabetics of type I and type II, either sex and aged between 15 and 70 years with stable diabetic therapy; fasting blood glucose <250 mg/dL; free from investigational drugs; had not suffered a myocardial infarction within the previous 6 months; and had either no hypertension or it was controlled. ... At the end of the study period, 16 treated and 9 control subjects had discontinued from the programe and, of these, 5 treated and 2 control subjects withdrew due to illness. No subjects discontinued due to side effects or abnormal laboratory parameters related to alitame treatment. Side-effects were observed in 29% of treated subjects and 25% of control subjects. Gastrointestinal disturbances were the most common side-effect. Incidence and severity of particular side-effects were relatively evenly distributed between the groups. No significant changes were noted in either the control or treated groups with respect to diabetic control, clinical chemistry, hematological or urinary parameters. No treatment-related effects were apparent from the physical examinations, blood pressure and pulse rate, temperature, body weight or EKG recordings. Alitame at a dose of 10 mg/kg/bw/day for 90 days was well tolerated by the type I and type II diabetic patients who continued in this study. There was no effect of alitame at this dose level on the ability to control serum glucose levels by these diabetic patients.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

在为期90天的双盲耐受性研究中，对77名接受治疗和80名对照的男女受试者进行了处理，要么给予阿丽甜（alitame）胶囊，分三次随餐服用，剂量为10毫克/千克体重/天，持续90天，要么以相同方式给予安慰剂。选择这个剂量是因为它比如果饮食中的所有蔗糖都被阿丽甜替代的估计每日摄入量高出10倍。在整个研究期间，通过访谈和观察对受试者进行了副作用评估。其他测试包括血压、体温、体重、心电图和眼底检查。还测量了各种临床病理参数。通过预给药以及在治疗第6周和第13周时测定氨基比林的消除动力学来估计微囊激活。在整个研究期间的不同时间点收集了血浆和尿液样本。4名接受治疗的受试者和2名对照受试者因副作用（治疗组受试者的唇部血管神经性水肿、斑丘疹、伴有红斑的荨麻疹，以及对照组受试者的耳鸣、干眼和腹痛）而退出了研究。在6个月后再次接受阿丽甜的挑战没有产生上述任何症状，使得过敏反应的可能性非常小。治疗组和对照组的血压、脉搏、体温或体重没有与治疗相关的变化。心电图和眼科检查均未发现异常。治疗组和对照组的血液学参数相似。在6周和13周测定的氨基比林消除率没有显示因阿丽甜治疗而增加的肝微粒体酶活性。

/HUMAN EXPOSURE STUDIES/ In a 90-day double-blind tolerance study, groups of male and female subjects (77 treated, 80 controls) were administered either alitame in capsules divided over three meals at a dose level of 10 mg/kg bw/day for 90 days, or placebo in the same manner. This dose was chosen because it is 10 times greater than the estimated daily intake if all sucrose in the diet were replaced with alitame. Subjects were assessed throughout the study period for side-effects (by interview and observation). Other tests included blood pressure, temperature, body weight, electrocardiogram, and ophthalmoscopic examination. Various clinical pathology parameters were also measured. Microsomal activation was estimated from the elimination kinetics of aminopyrine at pre-dosing and at weeks 6 and 13 of treatment. Plasma and urine samples were collected at various time points throughout the study. Four treated subjects and 2 control subjects discontinued from the study due to side effects (angioedema of the lips, maculopapular rash, urticaria (wheals) with erythema in treated subjects, and tinnitus, dry eyes and abdominal cramps in the control subjects). A rechallenge with alitame after 6 months produced none of the above symptoms, making the possibility of allergic reaction very unlikely. There were no treatment-related changes in blood pressure, pulse, temperature or body weight. Electrocardiograms and ophthalmological examinations were unremarkable. Hematological parameters were similar in treated and control subjects. Measurement of aminopyrine elimination rates at 6 and 13 weeks did not reveal any increase in hepatic microsomal enzyme activity due to alitame treatment.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

一组5只雄性CD-1小鼠通过灌胃给予单次剂量为50 mg/kg体重的14C-阿丽甜（alitame）的蒸馏水溶液。第二组5只雄性CD-1小鼠被喂食含有0.3%的14C-阿丽甜的饮食，相当于350 mg/kg体重。在灌胃剂量后，24小时内尿液中回收了77%的放射性。大约50%的给药剂量在4到20小时内被排出。粪便中的放射性未进行测量。在饮食给药后，60%的放射性在尿液中，32%在粪便中找到。

A group of 5 male CD-1 mice was administered by gavage a single dose of 50 mg/kg bw 14C-alitame in distilled water. A second group of 5 male CD-1 mice was fed a diet containing 14C-alitame at a concentration of 0.3%, equal to 350 mg/kg bw. Following the gavage dose, 77% of the radioactivity was recovered in urine in a 24-hour period. About 50% of the administered dose was excreted between 4 and 20 hr. Fecal radioactivity was not measured. Following dietary administration, 60% of the radioactivity was found in urine and 32% in feces.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

一只雄性长埃文斯大鼠通过胆管插管给予单次口服剂量50 mg/kg bw的14C-阿丽甜。收集胆汁和尿液共48小时。在第二个研究中，4只雄性和4只雌性长埃文斯大鼠给予单次口服剂量5 mg/kg bw的14C-阿丽甜。收集尿液和粪便共7天，并分析放射性。在单只动物研究中，83%的放射性被回收，其中14%在胆汁中，69%在48小时内的尿液中，表明广泛吸收。在群体研究中，大部分放射性在24小时内通过尿液回收（雄性83%，雌性95%）。在24小时内，雄性粪便放射性为20%，雌性为4%，之后检测到的很少。

A male Long-Evans rat with a bile duct cannula was administered a single oral dose of 50 mg/kg bw 14C-alitame. Bile and urine were collected for 48 hr. In a second study, 4 male and 4 female Long-Evans rats were administered a single oral dose of 5 mg/kg bw 14C-alitame. Urine and feces were collected for 7 days and analyzed for radioactivity. In the single animal study, 83% of the radioactivity was recovered, with 14% in bile and 69% in urine over 48 hr, indicating extensive absorption. In the group study, most of the radioactivity was recovered in urine (83% in males, and 95% in females) in a 24-hour period. Fecal radioactivity was 20% in males and 4% in females during 24 hr with little detected after that time.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在一项研究中，为了调查在大鼠体内的组织分布，一组24只雄性和24只雌性的长埃文斯大鼠通过灌胃接受了一次5毫克/千克体重的14C-阿斯巴甜单次剂量。将3只雄性和3只雌性大鼠分组，在2、6或24小时，以及2、3、7、14或29天时处死，并测定组织水平。在大多数组织中，清除的半衰期为3到6小时，到7天时水平已低于检测水平。眼部的放射性残留水平比其他组织下降得慢得多，到第29天时检测到了0.08毫克/千克的水平。

In a study to investigate tissue distribution in rats, a group of 24 male and 24 female Long-Evans rats received by gavage a single dose of 5 mg/kg bw 14C-alitame. Animals in groups of 3 males and 3 females were killed at 2, 6 or 24 hr, and at 2, 3, 7, 14 or 29 days and tissue levels determined. In most tissues, the half-life of clearance was 3 to 6 hr and the levels were below the level of detection by 7 days. Residue levels of radioactivity in the eyes decreased much more slowly than in other tissues and levels of 0.08 mg/kg were detected at day 29.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在对alitame的胎盘转移潜力进行研究时，怀孕的长埃文斯大鼠在妊娠第13天口服了1000毫克/千克体重的14C-alitame。在处理后的6或24小时，有四只动物被牺牲，检查母体血浆和胎儿的放射性。在6小时和24小时时，母体的血浆中放射性很高，此时在胎儿中也发现了高水平的放射性，这表明alitame发生了胎盘转移。

In a study to examine the potential for transplacental transfer of alitame, pregnant Long-Evans rats received a single oral dose of 1000 mg/kg bw 14C-alitame on day 13 of gestation. Four animals were sacrificed 6 or 24 hr after treatment and maternal plasma and fetuses were examined for radioactivity. Radioactivity was high in the plasma of dams at 6 and 24 hr, and high levels were also found in the fetuses at these times, indicating transplacental transfer of alitame.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 海关编码：
  2934999090

制备方法与用途

概述

阿力甜是一种以天冬氨酸和丙氨酸为原料合成的二肽类人工合成甜味剂。其甜度高达蔗糖的2000倍以上，比阿斯巴甜高10倍，具有口感好、甜度高和热量低的优点，是蔗糖的理想替代品之一。它的性质稳定，在食品行业中广泛使用，可添加于乳制品、冷冻饮品、蜜饯、饮料、胶基糖果及果冻等产品中。根据GB 2760-2014《食品安全国家标准 食品添加剂使用标准》，对上述食品的最大使用限量均有明确规定。

阿力甜一般被认为无毒且非刺激性物质，世界卫生组织（WHO）规定其日允许摄入量可达0.1 mg/kg。

应用

阿力甜广泛应用于乳制品、冷冻饮品、蜜饯、饮料和胶基糖果等食品中。作为强效甜味剂，它凭借出色的口感、高甜度和低热量等特性，在市场上的应用前景广阔。

制备

一种阿力甜标准物质的制备方法包括以下步骤：

1. 溶液制备：使用工业级阿力甜原料，溶于水中并通过超声波处理。随后进行过滤，确保溶液纯净。
2. 提取与纯化：通过特定的化学反应和提纯过程获得高纯度的阿力甜产品。
3. 干燥与封装：将制备好的阿力甜进行干燥，并进行严格的质量检测后封装。

化学性质

• 阿力甜为白色结晶性粉末，口感接近蔗糖，甜度高达蔗糖的2000倍。
• 其易溶于水（13.1%）、乙醇（61%）、甲醇（41.9%）和甘油（53.7%），微溶于氯仿。
• 不吸湿，耐热性及耐酸性均好。大鼠口LD₅₀大于5g/kg，ADI值待定（FAO/WHO, 1996年）。

用途

阿力甜作为一种新型、高甜度的甜味剂，在我国可用于胶基糖果、陈皮、话梅、话李和杨梅干等产品中，最大使用量为0.3g/kg；在饮料、冰淇淋及雪糕中的最大使用量为0.1g/kg。此外，还可作为餐桌甜味剂，最大用量为0.015g/包或片。

生产方法

阿力甜由天冬氨酸和丙氨酸等原料合成（USP4, 411, 925, 1983年10月25日）。

反应信息

• 作为反应物：
  描述：

  L-天门冬酰-N-(2,2,4,4-四甲基-3-硫杂环丁基)-D-丙氨酰胺 、 对甲苯磺酸 在 盐酸 作用下， 以 水 为溶剂， 反应 18.0h， 生成 3-(L-Aspartyl-D-alaninamido)-2,2,4,4-tetramethylthietane p-Toluenesulfonate
  参考文献：
  名称：

  WO2005/20930

  摘要：

  公开号：
• 作为产物：
  描述：

  (2R)-2-[[(2S)-4-methoxy-4-oxo-2-(phenylmethoxycarbonylamino)butanoyl]amino]propanoic acid 、 3-氨基-2,2,4,4-四甲基硫杂环丁烷 生成 L-天门冬酰-N-(2,2,4,4-四甲基-3-硫杂环丁基)-D-丙氨酰胺
  参考文献：
  名称：

  BRENNAN, THOMAS M.;HENDRICK, MICHAEL F.

  摘要：

  DOI：

文献信息

• [EN] TASTE MODULATING ALDEHYDES<br/>[FR] ALDÉHYDES MODULANT LE GOÛT
  申请人：TAKASAGO INT CORPORATION USA

  公开号：WO2018049352A1

  公开（公告）日：2018-03-15

  Aldehydes of formula (I) (X represents an alkyl or alkenyl group having up to 9 carbon atoms) for use in taste modulation and/or flavor compositions are provided. Specifically, the compounds of the presently disclosed subject matter provide effective and unexpected taste modulating properties. The taste modulation and/or flavor compositions can be incorporated into various consumer end products in particular in combination with high intensity sweeteners.

  提供化学式为(I)的醛类化合物（其中X代表含有最多9个碳原子的烷基或烯基基团），用于口感调节和/或风味组合。具体而言，本发明的化合物提供了有效和意外的口感调节特性。口感调节和/或风味组合物可以与高强度甜味剂结合，被纳入到各种消费者终端产品中。
• Sweetener compositions and uses thereof
  申请人：AJINOMOTO CO. INC

  公开号：US20040105928A1

  公开（公告）日：2004-06-03

  The present invention provides compositions containing one or more aspartyl dipeptide derivatives represented by formulas (1) and/or (2) mixed with another high intensity sweetner, such Aspartame, sugar, sugar alcohol, and oligosaccharide; food, beverages, and/or medicinal products containing these compositions, methods of using the compositions to impart sweetness in food, beverages, and/or medicinal products to impart sweetness or suppress a bitter taste; and methods of making the compositions and products.

  本发明提供了一种含有一个或多个由式(1)和/或式(2)表示的天冬氨酰二肽衍生物与另一种高强度甜味剂混合的组合物；含有这些组合物的食品、饮料和/或药品；使用这些组合物在食品、饮料和/或药品中赋予甜味或抑制苦味的方法；以及制备这些组合物和产品的方法。其中，另一种高强度甜味剂可以是阿斯巴甜、糖、糖醇和寡糖。
• Branched amides of L-aspartyl-D-amino acid dipeptides and compositions thereof
  申请人：PFIZER INC.

  公开号：EP0034876A2

  公开（公告）日：1981-09-02

  Amides of L-aspartyl-D-amino acid dipeptides of the formula and physiologically acceptable cationic and acid addition salts thereof wherein Ra is methyl, ethyl, n-propyl or isopropyl and R is a branched aliphatic, alicyclic or heterocyclic member which is branched at the alpha carbon atom (the carbon atom bearing the amide nitrogen atom) and also branched again at one or both of the beta carbon atoms, are potent sweeteners which are free from undesirable flavour qualities and of high stability in conventional food processing. Sweetening compositions and sweetened edible compositions of such amides are also claimed

  式中 L-天冬氨酰-D-氨基酸二肽的酰胺类 及其生理上可接受的阳离子盐和酸加成盐，其中 Ra 为甲基、乙基、正丙基或异丙基，R 为支链脂环族、脂环族或杂环族成员，该成员在 α 碳原子（含酰胺氮原子的碳原子）上有支链，在一个或两个β碳原子上也有支链。这种酰胺的甜味组合物和甜味可食用组合物也已申请专利。
• Synergistic sweetening compositions
  申请人：PFIZER INC.

  公开号：EP0139430A2

  公开（公告）日：1985-05-02

  Combination of 6-methyl-1,2,3-oxathiazin-4(3H)-one-2,2-dioxide (acesulfame) with 3-(L-aspartyl-D-alaninamido)-2,2,4,4-tetramethyhhietane masks the bitter taste of the oxathiazine and at the same time provides synergistic sweetness over a range of concentrations.

  将 6-甲基-1,2,3-噁噻嗪-4(3H)-酮-2,2-二氧化物（安赛蜜）与 3-(L-天冬氨酰-D-丙氨酰胺基)-2,2,4,4-四甲基硫杂环丁烷结合使用，可掩盖噁噻嗪的苦味，同时在一定浓度范围内提供协同甜味。
• Superior catalysts for preparation of 3-amino-2,2,4,4-tetramethylthietane via the Leuckart reaction
  申请人：PFIZER INC.

  公开号：EP0337652A1

  公开（公告）日：1989-10-18

  Boric acid or aluminum salts, especially aluminum chloride, aluminum sulfate and aluminum nitrate and hydrates of said salts, are superior catalysts for preparation of 3-amino-2,2,4,4-tetramethylthietane via the Leuckart reaction.

  硼酸或铝盐，尤其是氯化铝、硫酸铝和硝酸铝以及上述盐类的水合物，是通过勒卡特反应制备 3-氨基-2,2,4,4-四甲基硫杂环丁烷的优质催化剂。