γ-丁内酯 | 96-48-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 中文名称: γ-丁内酯
• 中文别名: gamma-丁内酯；1,4-丁内酯；4-羟基丁酸内酯；γ-羟基丁酸内酯；GBL
• 英文名称: 4-butanolide
• 英文别名: γ-butyrolactone；gamma-butyrolactone；butyrolactone；GBL；dihydrofuran-2(3H)-one；tetrahydrofuran-2-one；γ-valerolactone；ϒ-butyrolactone；1,4-butyrolactone；oxolan-2-one
• CAS: 96-48-0
• 化学式: C₄H₆O₂
• 分子量: 86.0904
• InChiKey: YEJRWHAVMIAJKC-UHFFFAOYSA-N

物化性质

• 稳定性/保质期：
  1. 避免与强氧化剂、强酸、强碱和强还原剂接触。溶于水、甲醇等，对金属无腐蚀性，可燃，低毒，易被皮肤吸收，应防止与皮肤接触。 化学性质：该物质在热碱作用下易发生水解，水解是可逆的，在pH＝7时又生成内酯；在酸性介质中水解较慢。 2. 本品属低毒类物质，对中枢神经有麻醉作用。大鼠经口LD₅₀=1800 mg/kg，对皮肤有刺激作用，其烟雾可刺激眼睛、黏膜和上呼吸道。 3. 存在于烤烟、白肋烟、香料烟的烟叶中，也存在于烟气中。 4. 还存在于杏、面包和咖啡中，并且是炒榛子挥发性香气成分之一。 5. 制备方法如下：在反应瓶中加入干燥乙腈2 mL，三甲基氯硅烷110 mg（1.0 mmol），氮气保护下于0 ℃加入硝酸银187 g（1.1 mmol）。搅拌反应1小时后倾出上清液（除去氯化银），在搅拌下加至CrO₃ 150 mg（1.5 mmol）的1 mL乙腈中，搅拌反应15分钟。然后，在冰水浴冷却下慢慢滴加THF（2）（1.0 mmol）溶于1 mL乙腈中的溶液，室温搅拌反应24小时。过滤、二氯甲烷洗涤后蒸出溶剂，得到粗品①（1）。硅胶柱纯化后收率为65%。注：该反应可能的机理如下。（参考书494页）[1]

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  6
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

ADMET

代谢

伽马-丁内酯通过乳酮酶迅速且定量地转化为伽马-羟基丁酸。已经在人血和鼠的血和肝脏中发现了乳酮酶，但在鼠的大脑、脾脏、肾脏、心脏、横膈膜、肺骨骼肌或胃肠道中并未发现。从人血浆中分离出的酶活性明显高于从鼠肝微粒体中分离出的酶。此外，人血清中的转化具有2.7 x 10^-2 M的米氏常数（Km值），因此比鼠血清中的转化（Km值为1.6 x 10^-2 M）更有效率。体外鼠血研究发现，伽马-丁内酯转化为伽马-羟基丁酸的半衰期不到一分钟。血清和血浆中发生水解，溶血的红细胞不活跃。在鼠血浆中，15分钟后水解率为92%，30分钟后达到100%，而在溶血的红细胞中，30分钟后的水解率仅为3%。在大鼠肝脏匀浆中，15分钟后水解百分比为87%，60分钟后为94%。在猫血中，伽马-丁内酯的水解速度比在鼠血中慢。兔子和豚鼠血清的样本也显示了伽马-丁内酯的水解（没有精确的细节）。各种培养基与1.3 x 10^-2 M伽马-丁内酯在37°C下孵化。

gamma-Butyrolactone undergoes rapid and quantitative conversion by lactonases, yielding gamma-hydroxybutyric acid. Lactonases have been identified in human blood and in the blood and liver of rats, but not in the rat brain, spleen, kidney, heart, diaphragm, lung skeletal muscle or gastrointestinal tract. The enzyme isolated from human plasma had a markedly higher activity than that isolated from rat liver microsomes. Moreover, conversion in human serum had a Km value of 2.7 x 10-2 M and thus was more efficient than in rat serum (Km value 1.6 x 10-2 M...). In vitro rat blood studies gave a half-life of less than one minute for the conversion of gamma-butyrolactone to gamma-hydroxybutyric acid. Hydrolysis took place in serum and plasma, hemolyzed erythrocytes being inactive. In rat plasma, hydrolysis was 92% after 15 minutes and 100% after 30 minutes, whereas in hemolyzed erythrocytes it was only 3% after 30 minutes. the percentage hydrolyzed in rat liver homogenate was 87% after 15 minutes and 94% after 60 minutes. In cat blood, hydrolysis of gamma-butyrolactone was slower than in rat blood. Samples of rabbit and guinea pig serum also showed hydrolysis of gamma-butyrolactone (no precise details). The various media were incubated with 1.3 x 10-2 M gamma-butyrolactone at 37 °C.

来源:Hazardous Substances Data Bank (HSDB)

代谢

...静脉注射给大鼠后，它会迅速转化为γ-羟基丁酸，这会导致中枢神经系统抑制。它也血液和肝脏中迅速水解为γ-羟基丁酸。

... After IV administration to rats it is converted rapidly into gamma-hydroxybutyric acid which causes depression of CNS. It is also rapidly hydrolyzed to gamma-hydroxybutyric acid in blood and liver.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在口服γ-丁内酯后观察到，γ-羟基丁酸也可以通过肠道中的非酶水解形成。

It was observed following oral administration of gamma-butyrolactone that gamma-hydroxybutyric acid can also be formed in the intestinal tract nonenzymatically by hydrolysis.

来源:Hazardous Substances Data Bank (HSDB)

代谢

四名健康受试者（2名男性，2名女性）每人饮用1克γ-丁内酯（溶于水；上午11点）。随后，收集了4小时内的每小时尿样并进行分析。观察到S-3,4-二羟基丁酸、乙二酸和γ-羟基丁酸的排泄增加。另一个代谢物可能是4-羟基-3-氧代丁酸的互变异构羟基环氧化物。根据研究者的说法，这些结果提示4-羟基丁酸通过β-氧化代谢。

Four healthy subjects (2 male, 2 female) each drank 1 g gamma-butyrolactone (dissolved in water; 11:00 a.m.). Subsequently, hourly urine samples were collected for 4 hours and analyzed. Increases were observed in the excretion of S-3,4-dihydroxybutyrate, glycolic acid and gamma-hydroxybutyrate. A further metabolite was probably the tautomeric hydroxyepoxide of 4-hydroxy-3-oxobutyrate. According to the investigator, these results suggested that 4-hydroxybutyrate is metabolized by beta-oxidation.

来源:Hazardous Substances Data Bank (HSDB)

代谢

伽马-丁内酯通过乳酸酶迅速且定量地转化为伽马-羟基丁酸（A627）。

Gamma-Butyrolactone undergoes rapid and quantitative conversion by lactonases, yielding gamma-hydroxybutyric acid (A627).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

γ-丁内酯迅速转化为γ-羟基丁酸。这可能是随后出现的中枢神经系统抑制剂作用的原因。γ-丁内酯是一种麻醉剂，通过拮抗神经末梢的递质释放，导致大脑多巴胺的选择性增加。它也是一种内源性脑代谢物，可能通过γ-氨基丁酸从谷氨酸衍生而来。γ-丁内酯与苦毒素受体（A566, A318）结合。

Gamma-butyrolactone is rapidly converted to gamma-hydroxybutyrate. This may account for the subsequent central nervous system depressant. Gamma-butyrolactone is an anesthetic that causes a selective increase in brain dopamine by antagonizing transmitter release from nerve terminal. It is also an endogenous brain metabolite that may be derived from glutamate through gamma-aminobutyrate. GBL binds to the picrotoxin receptor (A566, A318).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌性证据

评估：对于4-丁内酯对人类的致癌性，目前人类证据不足。有证据表明4-丁内酯在实验动物中缺乏致癌性。总体评估：4-丁内酯对人类的致癌性无法分类（第3组）。

Evaluation: There is inadequate evidence in humans for the carcinogenicity of 4-butyrolactone. There is evidence suggesting lack of carcinogenicity of 4-butyrolactone in experimental animals. Overall evaluation: 4-Butyrolactone is not classifiable as to its carcinogenicity to humans (Group 3).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌物分类

国际癌症研究机构致癌物：γ-丁内酯

IARC Carcinogenic Agent:gamma-Butyrolactone

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构（IARC）致癌物分类：第3组：无法归类其对人类致癌性

IARC Carcinogenic Classes:Group 3: Not classifiable as to its carcinogenicity to humans

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构专著：第11卷：（1976年）镉、镍、一些环氧化合物、其他工业化学品及对挥发性麻醉剂的一般考虑 增补第7卷：致癌性的整体评估：更新国际癌症研究机构专著第1至42卷，1987年；440页；ISBN 92-832-1411-0（已绝版） 第71卷：（1999年）对一些有机化学品、肼和过氧化氢（第一部分、第二部分、第三部分）的再评估

IARC Monographs:Volume 11: (1976) Cadmium, Nickel, Some Epoxides, Miscellaneous Industrial Chemicals and General Considerations on Volatile Anaesthetics Volume Sup 7: Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42, 1987; 440 pages; ISBN 92-832-1411-0 (out of print) Volume 71: (1999) Re-evaluation of Some Organic Chemicals, Hydrazine and Hydrogen Peroxide (Part 1, Part 2, Part 3)

来源:International Agency for Research on Cancer (IARC)

吸收、分配和排泄

伽马-丁内酯似乎很容易通过豚鼠皮肤被吸收。在大鼠中，至少有10%的施用剂量穿透了皮肤。在文献中没有找到描述伽马-丁内酯通过胃肠道或呼吸系统吸收的数据。伽马-丁内酯在哺乳动物体内的生物降解是迅速的。它在血液和肝脏中被水解为伽马-羟基丁酸。在大鼠中，伽马-羟基丁酸以二氧化碳的形式被排出。由于伽马-丁内酯快速代谢转化为对中枢神经系统有影响的伽马-羟基丁酸，因此它具有轻微的麻醉作用...

gamma-Butyrolactone appears to be readily absorbed through guinea pig skin. In rat, at least 10% of the applied dose penetrated the skin. Data describing the uptake of gamma-butyrolactone from the gastrointestinal or the respiratory system were not located in the literature. The biological degradation of gamma-butyrolactone in mammals is rapid. It is hydrolyzed to gamma-hydroxybutyric acid in the blood and liver. In rats, gamma-hydroxybutyric acid is excreted as CO2. gamma-Butyrolactone has a weak narcotic effect due to its fast metabolic conversion to gamma-hydroxybutyric acid, which has an effect on the central nervous system. ...

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

伽马-丁内酯...会...迅速水解成伽马-羟基丁酸...在大鼠中，通过吸入方式给予的(1-(14)C)-或(4-(14)C)-羟基丁酸盐会以(14)CO2的形式排出；大约66%的活性在6小时内排出，额外的10-20%在18小时内排出。

gamma-Butyrolactone ... is ... rapidly hydrolyzed to gamma-hydroxybutyric acid ... In rats, (1-(14)C)- or (4-(14)C)-hydroxybutyrate given by inhalation is excreted as (14)CO2; about 66% of activity was excreted in 6 hr and additional 10-20% within 18 hr.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

体重在200至250克的Sprague-Dawley雄性大鼠（每组实验6只）通过口服、腹腔注射（ip）或静脉注射（iv）途径接受了一次500 mg/kg体重的γ-丁内酯剂量。研究者们在给药后60分钟内分析了血液和大脑中的γ-丁内酯和其主要代谢物γ-羟基丁酸。口服给药后，3到5只大鼠在任意测量时间点的血液中γ-丁内酯水平都低于18微克/毫升的检测限，而其余大鼠的浓度在22.5至82.5微克/毫升之间，且与测量时间无关。主要代谢物γ-羟基丁酸的浓度在15分钟时达到峰值611微克/毫升，60分钟时仍为466微克/毫升。通过腹腔注射和静脉注射给药后，γ-丁内酯也非常迅速地被水解为γ-羟基丁酸。腹腔注射5分钟后，血液中γ-丁内酯的浓度为63微克/毫升，60分钟时为22.5微克/毫升；然而，在60分钟时，只有2只大鼠的浓度高于检测限。静脉注射后，5分钟的值为85微克/毫升，而在15分钟后γ-丁内酯就不再可检测。腹腔注射后γ-羟基丁酸的浓度从最大值694微克/毫升（5分钟值）下降到60分钟时的521微克/毫升，而静脉注射导致最大值为550微克/毫升（15分钟值），在609分钟时下降到430微克/毫升。在大脑中，口服给药后3分钟内γ-丁内酯的最大浓度为170微克/克，15至60分钟给药后检测到时间无关的γ-丁内酯浓度为14.8至29.1微克/克；γ-羟基丁酸的浓度在30分钟后达到峰值191.6微克/克，并在60分钟时下降到129.1微克/克（静脉注射后未测量大脑水平...）。数据允许得出结论，γ-丁内酯从胃肠道非常迅速且似乎完全吸收，并非常迅速地代谢为γ-羟基丁酸。

Male Sprague-Dawley rats (weighing 200 to 250 g, 6 rats/experiment) received a single gamma-butyrolactone dose of 500 mg/kg bw by the oral, ip or iv route. The investigators analyzed the blood and brain for gamma-butyrolactone and gamma-hydroxybutyric acid, the chemical's primary metabolite, for a period of 60 minutes after administration. Blood levels of gamma-butyrolactone after oral administration were below the limit of detection of 18 ug/mL in 3 and 5 out of 6 animals, independently of the time of measurement, whereas the remaining animals had time-independent levels between 22.5 and 82.5 ug/mL. The levels observed for the primary metabolite, gamma-hydroxybutyric acid, reached a peak value of 611 ug/mL at 15 minutes and were still 466 ug/mL at 60 minutes. Following ip and iv administration, there was also very rapid hydrolysis of gamma-butyrolactone to gamma-hydroxybutyric acid. The blood gamma-butyrolactone levels was 63 ug/mL 5 minutes after ip injection, while it was 22.5 ug/mL at 60 minutes; however, only 2 out of 6 animals had levels above the limit of detection at 60 minutes. Upon iv injection, the 5-minute value was 85 ug/mL, whereas gamma-butyrolactone was no longer detectable after 15 minutes. The concentration levels of gamma-hydroxybutyric acid seen after ip dosing dropped from a maximum of 694 ug/mL (5-minute value) 521 ug/mL at 60 minutes, whereas iv injection led to a maximum level of 550 ug/mL (15-minute value) which dropped to 430 ug/mL at 609 minutes. In brain, oral dosing resulted in maximum gamma-butyrolactone levels of 170 ug/g were found after 3 minutes, and time-independent gamma-butyrolactone levels of 14.8 to 29.1 ug/g were detected 15 to 60 minutes after dosing; the concentration of gamma-hydroxybutyric acid reached its peak of 191.6 ug/g after 30 minutes and fell to 129.1 ug/g at 60 minutes (no brain levels were measured after iv administration... .The data permit the conclusion that gamma-butyrolactone is very rapidly and apparently completely absorbed from the gastrointestinal tract and undergoes very rapid metabolism to gamma-hydroxybutyric acid.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

伽马-丁内酯的吸收研究在至少3只，通常为4只，体重在260至340克的雄性Sprague-Dawley大鼠（未提供精确的大鼠数量）上进行了。每剂量和治疗类型。伽马-丁内酯（纯度未指定）通过胃插管口服给药，剂量水平为1.58和6.34毫摩尔（大约136和546毫克）/千克体重，心脏内给药为1.58毫摩尔或静脉给药为6.34毫摩尔/千克体重。在给药后立即开始，对血浆中的伽马-丁内酯进行了总共3至8小时的分析。分析程序无法区分伽马-丁内酯和伽马-羟基丁酸，后者是伽马-丁内酯的主要代谢物，因为早期的研究者在给大鼠服用伽马-丁内酯后只能在血液中检测到伽马-羟基丁酸。当伽马-丁内酯以136毫克/千克体重的剂量心脏内给药时，血浆水平在给药时立即达到500微克/毫升，30分钟后约为400微克/毫升，2小时后略高于100微克/毫升，但在2.5小时后降至50微克/毫升以下。口服给药136毫克/千克体重后，血浆水平在15至30分钟内达到大约350微克/毫升的峰值，然后以0.3小时的消除半衰期下降，在3小时内降至大约25微克/毫升。口服给药伽马-丁内酯546毫克/千克体重后，血浆水平在约3小时内保持在≥1000微克/毫升，与静脉给药相同剂量的情况相同。口服给药4小时后，血浆浓度约为800微克/毫升，6小时后约为450微克/毫升，8小时后略高于100微克/毫升。静脉注射后，血浆水平下降得更快一些，8小时后达到大约55微克/毫升（图形表示不允许更准确的读数）。在经皮吸收研究中，体重在275至525克的雄性Sprague-Dawley大鼠将未稀释的伽马-丁内酯涂抹在机械或机械和化学脱毛的皮肤上，剂量为6.34毫摩尔（大约546毫克）/千克体重，持续4小时。经皮吸收的速率取决于预处理大鼠皮肤的方法。当皮肤仅被剃毛时，血浆浓度缓慢上升，在大约1.5至2小时后达到最大水平，约为150微克/毫升；当皮肤剃毛后并用商业脱毛剂（基于巯基乙酸的配方）处理时，伽马-丁内酯应用后仅在大约10分钟就达到了大约175微克/毫升的最大血浆浓度。根据血浆浓度-时间曲线下的面积（AUC值），发现相对于静脉给药后得到的值，口服给药的剂量吸收分数为85和98%，而机械或机械和化学脱毛皮肤上的经皮应用吸收分数为7和11%。

... Studies on the absorption of gamma-butyrolactone were carried out in at least 3, usually 4, male Sprague-Dawley rats (weighing 260 to 340 g; no precise details of the number of rats used)/dose and type of treatment. gamma-Butyrolactone (purity not specified) was administered orally by gastric intubation at dose levels of 1.58 and 6.34 mmol (approximately 136 and 546 mg)/kg bw, intracardially at 1.58 mmol or iv at 6.34 mmol/kg bw. Starting immediately after administration, the plasma was analyzed for gamma-butyrolactone over a total period of 3 to 8 hours. The analytical procedure did not distinguish between gamma-butyrolactone and gamma-hydroxybutyric acid, the primary metabolite of gamma-butyrolactone, as earlier studies by the investigators had detected only gamma-hydroxybutyric acid in rat blood after administration of gamma-butyrolactone. When gamma-butyrolactone was given intracardially at 136 mg/kg bw, the plasma levels was 500 ug/mL immediately upon dosing, about 400 ug/mL after 30 minutes and slightly more than 100 ug/mL after 2 hours but then dropped to below 50 ug/mL after 2.5 hours. After oral administration of 136 mg/kg bw, plasma levels reached their peak of approximately 350 ug/mL at 15 to 30 minutes before declining with an elimination half-life of 0.3 hours to approximately 25 ug/mL within 3 hours. Plasma levels after oral administration of gamma-butyrolactone at 546 mg/kg bw remained at > or =1000 ug/mL for approximately 3 hours, as they did after iv administration of the same dose. Four hours after oral dosing, the plasma concentration was about 800 ug/mL, while it was approximately 450 ug/mL after 6 hours and slightly above 100 ug/mL after 8 hours. Subsequent to iv injection, plasma levels dropped somewhat more rapidly, reaching approximately 55 ug/mL after 8 hours (the graphical representation does not permit a more accurate reading). In percutaneous absorption studies, male Sprague-Dawley rats (weighting 275 to 525 g) had undiluted gamma-butyrolactone applied to the mechanically or mechanically and chemically depilated skin at 6.34 mmol (approximately 546 mg)/kg bw for 4 hours. The rate of percutaneous absorption depended on the method employed to pretreat the rat skin. When the skin was only shaved, the plasma concentrations rose slowly, reaching maximum levels of approximately 150 ug/mL after 1.5 to 2 hours; when the skin was shaved an subsequently treated with a commercial depilating agent (a thioglycolic acid-based formulation), the maximum plasma concentration of approximately 175 ug/mL was reached only approximately 10 minutes after gamma-butyrolactone application. Based on the areas under the plasma concentration-time curves (AUC values) it was found that, relative to the value obtained after iv administration, the fractions of dose absorbed were 85 and 98% upon oral administration, and 7 and 11% upon dermal application onto the mechanically or mechanically and chemically depilated skin, respectively.

来源:Hazardous Substances Data Bank (HSDB)

制备方法与用途

制备方法

1. 顺酐加氢法：该法是70年代发展的先进工艺，通过一段加氢反应，能以任意比例生产四氢呋喃和γ-丁内酯。通常的比例是四氯呋喃：γ-丁内酯=3-4:1。生产企业较多但规模较小，平均年产量约为300吨。该法占国内总产能的30%。

2. 1,4-丁二醇脱氢法：反应器为列管式，装填片状铜催化剂（以氧化锌为载体）。反应温度控制在230-240℃。反应产物粗γ-丁内酯经减压蒸馏得成品，收率可达77%以上。

3. 1,4-丁二醇制备法：以1,4-丁二醇为原料，先预热，与氢气在铜催化剂存在下反应，温度控制在230～240℃，得到γ-丁内酯粗品，经减压蒸馏得产品。

4. 顺酐加氢制备法：目前常用顺酐法经过加氢生成丁二酸酐，再进一步加氢脱水获得产品。

5. 烯丙醇法制备法：以芳烃为溶剂、铑络合物为催化剂，将烯丙醇与原料气（H2+CO)醛化，以骨架镍催化加氢得1,4-丁二醇，进而制得γ-丁内酯并联产四氢呋喃。

合成制备方法

1. 顺酐加氢法：该工艺是70年代发展的先进技术，通过一次加氢反应能任意比例生产四氢呋喃和γ-丁内酯。常用的比例为四氯呋喃：γ-丁内酯=3-4:1。生产企业较多但规模小，平均年产量约为300吨。该方法占国内总产能的30%。

2. 1,4-丁二醇脱氢法：反应器设计为列管式，填充片状铜催化剂（以氧化锌为载体）。控制反应温度在230-240℃之间。粗γ-丁内酯经减压蒸馏后获得成品，收率通常超过77%。

3. 1,4-丁二醇制备法：利用1,4-丁二醇作为原料，先预热，与氢气在铜催化剂存在下反应，温度控制在230～240℃之间，产生γ-丁内酯粗品。然后通过减压蒸馏得到产品。

4. 顺酐加氢制备法：目前常用的方法是将顺酐经过加氢生成丁二酸酐，再进一步加氢脱水获得目标产物。

5. 烯丙醇法制备法：使用芳烃作为溶剂和铑络合物作为催化剂，将烯丙醇与原料气（H2+CO)醛化，通过骨架镍催化加氢得1,4-丁二醇。进而制得γ-丁内酯并联产四氢呋喃。

用途简介

γ-丁内酯主要用于气相色谱固定液，最高使用温度为30℃，溶剂采用甲醇。它能够分离和分析烃类及各种含氧化合物、永久性气体；合成聚乙烯吡咯烷酮、DL-甲硫氨酸、六氢吡啶、苯丁酸和硫代乙酸等中间体；作为聚丙烯腈、乙酸纤维、聚甲基丙烯酸甲酯和聚苯乙烯的溶剂。此外，它还具有良好的抗氧性、增塑性、萃取性、吸收性、分散性和固色作用，在医药行业中可作麻醉剂及镇静剂，并可用于合成环丙沙星和干扰素等药物；在农林业中是植物生长剂和杀虫剂的中间体；也可用于电池、电容器制作，彩卷成色等。

反应信息

• 作为反应物：
  描述：

  γ-丁内酯 在 aldehyde reductase 、 环丁基胺 、 cyclohexanone monooxygenase from Thermocrispum municipale DSM 44069 、 lactonase 、 nicotinamide adenine dinucleotide phosphate 、 transaminase from Silicibacter pomeroyi 作用下， 以 aq. buffer 为溶剂， 反应 24.0h， 生成 4-氨基丁酸
  参考文献：
  名称：

  从环烷基胺生物合成尼龙单体的集成辅因子/副产物回收级联反应

  摘要：

  我们报道了一种高度原子高效的辅因子/副产品回收级联反应，采用环烷基胺作为合成尼龙构件的多方面原料。使用大肠杆菌全细胞以及纯化的酶进行的反应可在不同的底物浓度下分别产生大于80％和95％的所需ω-氨基酸的出色转化率。通过使用工程化的生物催化剂证明了该串联生物催化级联的适用性以产生相应的内酰胺。例如，通过使用全细胞生物催化剂，由10 mM环己胺合成了有价值的聚合物β-己内酰胺，其转化率为75％。这种级联反应可以替代基于生物的ω-氨基酸和相应内酰胺化合物的生产。

  DOI：

  10.1002/anie.202012658
• 作为产物：
  描述：

  丁二酸酐 在 tris(triphenylphosphine)ruthenium(II) chloride 氢气 作用下， 以 various solvent(s) 为溶剂， 170.0 ℃ 、100.0 kPa 条件下， 生成 γ-丁内酯
  参考文献：
  名称：

  钌配合物催化新型制备γ-丁内酯

  摘要：

  γ-丁内酯（以下简称GBL）是通过液相进行马来酸酐（MAH）的两步加氢而制得的：第一步是将MAH加氢为琥珀酸酐（SAH），然后将SAH加氢为GBL。第二阶段。已经使用均相催化剂研究了后者的氢化。开发了由Ru（acac）3，P（辛基）3和对甲苯磺酸（p -TsOH）组成的新型钌催化剂体系，用于SAH的加氢反应，具有优异的催化性能，对GBL的选择性超过95％以上活性高于文献报道。发现p-TsOH不仅在提高反应速率方面而且在提高选择性方面都起着重要作用。对-TsOH诱导Ru络合物发生结构变化，导致阳离子变化，从而显示出更高的催化剂活性。它也防止了由游离P（辛基）3催化的不希望的副反应，从而导致对GBL的高选择性。研究了生产GBL的方法。该方法的一些新颖特征包括Ru配合物的外部制备方法，偶联反应以及分离以去除H 2 O（SAH的氢化产物）以提高反应速率的方法。还开发了催化剂回收系统以回收超过90％的催化剂。

  DOI：

  10.1006/jcat.2000.2945
• 作为试剂：
  描述：

  4,4’-二酰氯二苯醚 、 N-(2-氨基-4-硝基苯基)-n-苯胺 在 三乙胺 、 γ-丁内酯 、 对甲苯磺酸 作用下， 以 四氢呋喃 为溶剂， 反应 22.0h， 以81.5%的产率得到2,2'-(4,4'-oxybiphenyl)bis(1-phenyl-5-nitrobenzimidazole)
  参考文献：
  名称：

  一种含双N-取代苯并咪唑二胺及其制备方法和应用

  摘要：

  本发明提供了一种含双N‑取代苯并咪唑二胺及其制备方法和应用，属于有机合成技术领域。本发明提供的含双N‑取代苯并咪唑二胺中双苯并咪唑环都带有侧基，双N‑取代苯并咪唑的引入在保留传统苯并咪唑端氨基较强亲和性的同时，可以增加该类分子侧基的空间位阻效应，进而提高利用本发明的二胺单体制备的聚合材料的热学性能和溶解性；此外，本发明在双N‑取代苯并咪唑环之间引入了柔性基团或大体积侧基，进一步增加该类分子的柔性和空间位阻效应，进一步提高本发明的二胺单体制备的聚合材料的溶解性。

  公开号：

  CN112778211A

文献信息

• SYNTHESIS OF CYCLIC AMIDINES
  申请人：Lentzen George

  公开号：US20110178292A1

  公开（公告）日：2011-07-21

  The invention relates to an innovative method for synthesis of cyclic amidines. The synthesis starts from a β-, γ- or δ-lactone which is twofold brominated. After esterification of the carboxyl function, the bromine atoms are nucleophilically substituted and the corresponding diamino compound is obtained. The ring closure to the cyclic amidine is accomplished subsequently by reaction with orthoester, imidate or thioimidate. Owing to interposing additional steps for recovery of the diamino compound in enantiomerically pure form, the enantiomers of the cyclic amidines can be stereoselectively synthesized.

  该发明涉及一种合成环氨基甲酸盐的创新方法。合成从β-、γ-或δ-内酯开始，该内酯经过双溴化。在羧基酯化后，溴原子被亲核取代，得到相应的二氨基化合物。随后通过与正酯、亚胺酯或硫代亚胺的反应实现环氨基甲酸盐的环闭合。由于插入额外步骤以以对映纯形式回收二氨基化合物，因此可以立体选择性地合成环氨基甲酸盐的对映体。
• Total Synthesis of (−)-21-Isopentenylpaxilline
  作者：Amos B. Smith、Haifeng Cui

  DOI：10.1021/ol027575g

  日期：2003.2.1

  [structure: see text] The total synthesis of (-)-21-isopentenylpaxilline (1) has been achieved. Key elements of the synthesis include the stereocontrolled construction of the advanced eastern hemisphere (-)-5, a highly efficient union of the eastern and western fragments (-)-5 and 4, respectively, exploiting our 2-substituted indole synthesis, and a new protocol for the construction of ring C.

  [结构：见正文]已完成（-）-21-异戊烯基帕西林（1）的全合成。合成的关键元素包括先进的东半球（-）-5的立体控制结构，利用我们的2取代的吲哚合成技术分别高效合成东部和西部碎片（-）-5和4的方法，以及用于构建C环的新协议。
• Metal‐Free Synthesis of <i>N</i> ‐Aryl Amides using Organocatalytic Ring‐Opening Aminolysis of Lactones
  作者：Wusheng Guo、José Enrique Gómez、Luis Martínez‐Rodríguez、Nuno A. G. Bandeira、Carles Bo、Arjan W. Kleij

  DOI：10.1002/cssc.201700415

  日期：2017.5.9

  Catalytic ring‐opening of bio‐sourced non‐strained lactones with aromatic amines can offer a straightforward, 100 % atom‐economical, and sustainable pathway towards relevant N‐aryl amide scaffolds. Herein, the first general, metal‐free, and highly efficient N‐aryl amide formation is reported from poorly reactive aromatic amines and non‐strained lactones under mild operating conditions using an organic

  生物来源的非应变内酯与芳族胺的催化开环可以提供一种直接的，100％原子经济且可持续的通往相关N芳基酰胺支架的途径。在此，据报道，在温和的操作条件下，使用有机双环胍催化剂，由反应性较差的芳族胺和非应变的内酯首次形成了无金属且高效的N-芳基酰胺。该协议具有很高的应用潜力，例如与药物相关的分子的形式合成。
• Reactions of methyl anthranilate with ethyl γ-bromobutyrate
  作者：I. McCall、G. R. Proctor、L. Purdie

  DOI：10.1039/j39700001126

  日期：——

  When methyl anthranilate and ethyl γ-bromobutyrate are heated together, various products are formed: above 125° the main product is a yellow compound for which a 7b,12b-diazabenz[e]aceanthrylene structure is postulated.

  当邻氨基苯甲酸甲酯和γ-溴丁酸乙酯一起加热时，形成各种产物：在125°以上，主要产物是黄色化合物，假定该化合物具有7b，12b-二氮杂苯并[ e ]乙炔结构。
• A facile two synthon approach to the camptothecin skeleton
  作者：H.G.M. Walraven、U.K. Pandit

  DOI：10.1016/0040-4020(80)80022-6

  日期：1980.1

  A synthesis of deethyldesoxycamptothecin via the reaction of two readily accessible synthons is described. One of the synthons constitutes the ABC ring system of camptothecin, while the second provides all the C atoms of the rings D and E. The synthetic approach is suited for the total synthesis of camptothecin analogues.

  描述了通过两个易于接近的合成子的反应合成去乙基脱氧喜树碱的方法。其中一个合成子构成喜树碱的ABC环系统，而第二个合成子则提供了环D和E的所有C原子。合成方法适用于喜树碱类似物的全合成。

表征谱图