(2S)-3-(3,4-dihydroxyphenyl)-2-{[(2E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy}propanoic acid | 179188-11-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (2S)-3-(3,4-dihydroxyphenyl)-2-{[(2E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy}propanoic acid
• 英文别名: (-)-rosmarinic acid；(E)-rosmarinic acid；rosmarinic acid；(S)-rosmarinic acid；(R)-rosmarinic acid；(2S)-3-(3,4-dihydroxyphenyl)-2-[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxypropanoic acid
• CAS: 179188-11-5
• 化学式: C₁₈H₁₆O₈
• 分子量: 360.32
• InChiKey: DOUMFZQKYFQNTF-GIZXNFQBSA-N

物化性质

• 沸点：
  694.7±55.0 °C(Predicted)
• 密度：
  1.547±0.06 g/cm3(Predicted)
• 颜色/状态：
  Crystalline solid
• 熔点：
  171-175 °C
• 溶解度：
  Soluble in ethanol, DMSO or dimethyl formamide to approximately 25 mg/mL
• 蒸汽压力：
  1.1X10-13 mm Hg at 25 °C (est)
• 解离常数：
  pKa = 3.57 (est)
• 碰撞截面：
  172.7 Ų [M-H]- [CCS Type: DT, Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  145
• 氢给体数：
  5
• 氢受体数：
  8

ADMET

代谢

口服给药的鼠尿液中鉴定出了7种代谢物，分别是：反式咖啡酸4-O-硫酸盐（1）、反式间-香豆酸3-O-硫酸盐（2）、反式阿魏酸4-O-硫酸盐（3）、反式咖啡酸（4）、间羟基苯丙酸（5）、反式间-香豆酸（6）和未改变的迷迭香酸（7），这些通过光谱和化学数据进行了鉴定。口服给药48小时后，尿液中排出的1-7号代谢物的总累积量约为给药剂量的31.8%。另一方面，在胆汁中并未发现归属于迷迭香酸的代谢物。因此，可以得出结论，口服给药的迷迭香酸主要通过尿液排出，而不是胆汁，代谢过程中涉及到酯键的断裂、选择性的对位去羟基化、甲基化和硫酸结合。代谢物2、3、5和6也在血浆中被检测到。

The urine of rats administered rosmarinic acid (7) orally contained seven metabolites, which were identified as trans-caffeic acid 4-O-sulfate (1), trans-m-coumaric acid 3-O-sulfate (2), trans-ferulic acid 4-O-sulfate (3), trans-caffeic acid (4), m-hydroxyphenylpropionic acid (5), trans-m-coumaric acid (6), and unchanged rosmarinic acid (7) by spectroscopic and chemical data. The total cumulative amount of 1-7 excreted in the urine 48 h after the oral administration of rosmarinic acid was approximately 31.8% of the dose administered. On the other hand, the metabolites attributed to rosmarinic acid could not be found in the bile. Orally administered rosmarinic acid may thus be concluded to be excreted in the urine rather than in the bile, with cleavage of ester bonds, selective para-dehydroxylation, methylation, and sulfate-conjugation. Metabolites 2, 3, 5, and 6 were also detected in the plasma.

来源:Hazardous Substances Data Bank (HSDB)

代谢

迷迭香酸是紫草科和唇形科植物中积累的主要羟基肉桂酸酯。通过差异显示法从培养的红花紫草细胞中分离出一个细胞色素P450 cDNA，根据推导的氨基酸序列，基因产物被命名为CYP98A6。在酵母中表达后，显示P450催化了4-香豆酰-4'-羟基苯乳酸的3-羟基化，这是导致迷迭香酸生成的最后两个步骤之一。通过向红花紫草细胞中添加酵母提取物或甲基茉莉酸，CYP98A6的表达水平显著提高，其表达模式反映了诱导子引起的迷迭香酸产量变化，表明CYP98A6在迷迭香酸生物合成调控中发挥重要作用。

Rosmarinic acid is the dominant hydroxycinnamic acid ester accumulated in Boraginaceae and Lamiaceae plants. A cytochrome P450 cDNA was isolated by differential display from cultured cells of Lithospermum erythrorhizon, and the gene product was designated CYP98A6 based on the deduced amino acid sequence. After expression in yeast, the P450 was shown to catalyze the 3-hydroxylation of 4-coumaroyl-4'-hydroxyphenyllactic acid, one of the final two steps leading to rosmarinic acid. The expression level of CYP98A6 is dramatically increased by addition of yeast extract or methyl jasmonate to L. erythrorhizon cells, and its expression pattern reflected the elicitor-induced change in rosmarinic acid production, indicating that CYP98A6 plays an important role in regulation of rosmarinic acid biosynthesis.

来源:Hazardous Substances Data Bank (HSDB)

代谢

本研究的目的是在健康人体内确定迷迭香酸（RA）在一次摄入紫苏提取物（PE）后的吸收、代谢和尿液排泄情况。共有六名健康男性（平均年龄37.2 ± 6.2岁，平均体重指数22.0 ± 1.9 kg/m²）参加了这项交叉设计的研究，他们在摄入含有200毫克RA的PE和安慰剂之间有10天的间隔。在摄入前和指定的时间间隔收集血液样本，而尿液样本则是在摄入后0-6小时、6-24小时和24-48小时期间收集。通过LC-MS测量血浆和尿液中RA及其相关代谢物。摄入PE后，在尿液中检测到RA、甲基化RA（甲基-RA）、咖啡酸（CAA）、阿魏酸（FA）和微量的香豆酸（COA）。在血浆中，检测到RA、甲基-RA和FA，分别在摄入PE后的0.5小时、2小时和0.5小时达到最大水平。血浆和尿液中这些成分的大部分以结合形式（葡萄糖醛酸苷和/或硫酸盐）存在。RA及其相关代谢物在尿液中的排泄比例占到了总剂量的6.3 ± 2.2%，约75%的这些成分在摄入PE后的6小时内被排泄。

The aim of this study in healthy humans was to determine the absorption, metabolism, and urinary excretion of rosmarinic acid (RA) after a single intake of perilla extract (PE). Six healthy men (mean age 37.2 +/- 6.2 y and mean body mass index 22.0 +/- 1.9 kg/sq m) were enrolled in the study that was a crossover design involving single intakes of PE containing 200 mg RA and placebo with a 10 day interval between treatments. Blood samples were collected before intake and at designated time intervals, while urine samples were collected over the periods 0-6 hr, 6-24 hr and 24-48 hr after intake. RA and its related metabolites in plasma and urine were measured by LC-MS. RA, methylated RA (methyl-RA), caffeic acid (CAA), ferulic acid (FA) and a trace of m-coumaric acid (COA) were detected in the urine after intake of PE. In plasma, RA, methyl-RA and FA were detected, with maximum levels obtained 0.5, 2 and 0.5 hr after intake of PE, respectively. The majority of these components in both plasma and urine were present as conjugated forms (glucuronide and/or sulfated). The proportion of RA and its related metabolites excreted in the urine was 6.3 +/- 2.2% of the total dose, with approximately 75% of these components being excreted within 6 hr after intake of PE.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

RA（迷迭香酸）是一种咖啡酸酯，具有在高果糖饮食诱导的胰岛素抵抗（IR）模型中的增敏和抗氧化作用。本研究探讨了RA补充是否能够预防高果糖饮食大鼠（FFR）的心脏异常和高血压。经过60天的高果糖饮食（60克/100克）的大鼠表现出代谢异常，血浆和心脏脂质水平升高，全身胰岛素抵抗增加。FFR的心脏抗氧化剂水平和血浆的还原力显著降低，同时脂质过氧化和蛋白质氧化产物的水平增加。FFR的血浆中肌钙蛋白T、肌酸激酶-MB、天冬氨酸转氨酶和乳酸脱氢酶显著升高。从第16天开始给FFR补充RA（10毫克/千克）显著改善了胰岛素敏感性，降低了脂质水平、氧化损伤和烟酰胺腺嘌呤二核苷酸磷酸还原酶的p22phox亚基的表达，并预防了心肌肥大。RA还通过降低内皮素-1和血管紧张素转换酶活性以及增加一氧化氮水平，降低了果糖诱导的血压升高。组织学检查显示，RA补充的FFR心肌损伤减少。这些发现表明，RA通过其抗氧化性质作为一种血管活性物质和心脏保护剂发挥作用。因此，RA可能有助于减少与IR相关的心血管风险。

Rosmarinic acid (RA), a caffeic acid ester, has insulin-sensitizing and antioxidant effects in high fructose-fed model of insulin resistance (IR). This study investigated whether RA supplementation prevents cardiac abnormalities and hypertension in fructose-fed rats (FFR). Rats fed with fructose diet (60 g/100 g) for 60 days exhibited metabolic abnormalities and rise in plasma and cardiac lipids and whole body IR. The levels of cardiac antioxidants and plasma ferric reducing antioxidant power were significantly reduced in FFR concomitant with increased levels of lipid peroxidation and protein oxidation products. A significant rise in troponin T, creatine kinase-MB, aspartate transaminase, and lactate dehydrogenase in plasma of FFR was noted. RA supplementation to FFR (10 mg/kg from the 16th day) significantly improved insulin sensitivity, reduced lipid levels, oxidative damage, and the expression of p22phox subunit of nicotinamide adenine dinucleotide phosphate reduced oxidase, and prevented cardiac hypertrophy. Fructose-induced rise in blood pressure was also lowered by RA through decrease in endothelin-1 and angiotensin-converting enzyme activity and increase in nitric oxide levels. Histology revealed a reduction in myocardial damage in RA-supplemented FFR. These findings suggest that RA acts as a vasoactive substance and a cardioprotector through its antioxidant property. Thus, RA may be useful in reducing the cardiovascular risk associated with IR.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

流行病学和实验研究已经表明，柴油机尾气颗粒（DEP）可能与近年来肺部疾病的增加有关。DEP已被证实能够产生活性氧种。通过气管内注入DEP会在小鼠中诱导肺部炎症和水肿。迷迭香酸是一种天然存在的多酚，具有抗氧化和抗炎活性。本研究调查了迷迭香酸对通过气管内给药DEP（500微克/体重）在小鼠中诱导的肺损伤的影响。口服补充迷迭香酸（2毫克/体重，连续3天）抑制了DEP诱导的肺损伤，这种损伤的特点是中性粒细胞的扣押和间质水肿。DEP增强了肺中角蛋白化学吸引剂（KC）、白细胞介素-1beta、单核细胞化学吸引蛋白-1和巨噬细胞炎症蛋白-1alpha的表达，而迷迭香酸的治疗抑制了这些表达。DEP还增强了肺中iNOS mRNA的表达和硝基酪氨酸以及8-OHdG的形成，这些也被迷迭香酸抑制。这些结果提示，迷迭香酸通过减少促炎分子表达来抑制DEP诱导的肺损伤。迷迭香酸的抗氧化活性也可能对其保护效果有所贡献。

Epidemiological and experimental studies have suggested that diesel exhaust particles (DEP) may be involved in recent increases in lung diseases. DEP has been shown to generate reactive oxygen species. Intratracheal instillation of DEP induces lung inflammation and edema in mice. Rosmarinic acid is a naturally occurring polyphenol with antioxidative and anti-inflammatory activities. /This/ investigated the effects of rosmarinic acid on lung injury induced by intratracheal administration of DEP (500 ug/body) in mice. Oral supplementation with administration of rosmarinic acid (2 mg/body for 3 d) inhibited DEP-induced lung injury, which was characterized by neutrophil sequestration and interstitial edema. DEP enhanced the lung expression of keratinocyte chemoattractant (KC), interleukin-1beta, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1alpha, which was inhibited by treatment with rosmarinic acid. DEP enhanced expression of iNOS mRNA and formation of nitrotyrosine and 8-OHdG in the lung, which was also inhibited by rosmarinic acid. These results suggest that rosmarinic acid inhibits DEP-induced lung injury by the reduction of proinflammatory molecule expression. Antioxidative activities of rosmarinic acid may also contribute to its protective effects.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

迷迭香酸（RA），一种多酚类植物化学物质，是一种天然的脯氨酰寡肽酶抑制剂。/当前研究/发现，RA在由脂多糖（LPS）诱导的急性肺损伤（ALI）的体内模型中展现了强大的抗炎效果。小鼠在挑战前一小时用RA预处理，剂量为0.5 mg/kg LPS。在给予LPS后24小时，获取支气管肺泡灌洗液（BALF）以测量促炎介质和总细胞数。与LPS组相比，RA显著减少了LPS诱导的TNF-a、IL-6和IL-1beta的产生。当用RA（5、10或20 mg/kg）预处理时，肺组织的肺湿重/干重（W/D）比率和BALF中的总细胞数、中性粒细胞和巨噬细胞数量显著减少。此外，RA可能通过增强氧化酶二酶（SOD）活性来应对LPS诱导的ALI的炎症反应。/作者/进一步证明，RA通过剂量依赖性地抑制ERK/MAPK信号传导，在ALI的体内模型中发挥抗炎作用...

Rosmarinic acid (RA), a polyphenolic phytochemical, is a natural prolyl oligopeptidase inhibitor. /The present study/ found that RA exerted potent anti-inflammatory effects in in vivo models of acute lung injury (ALI) induced by lipopolysaccharide (LPS). Mice were pretreated with RA one hour before challenge with a dose of 0.5 mg/kg LPS. Twenty-four hours after LPS was given, bronchoalveolar lavage fluid (BALF) was obtained to measure pro-inflammatory mediator and total cell counts. RA significantly decreased the production of LPS-induced TNF-a, IL-6, and IL-1beta compare with the LPS group. When pretreated with RA (5, 10, or 20 mg/kg) the lung wet-to-dry weight (W/D) ratio of the lung tissue and the number of total cells, neutrophils and macrophages in the BALF were decreased significantly. Furthermore, RA may enhance oxidase dimutase (SOD) activity during the inflammatory response to LPS-induced ALI. And /the authors/ further demonstrated that RA exerts anti-inflammation effect in vivo models of ALI through suppresses ERK/MAPK signaling in a dose dependent manner...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

本工作的目的是研究迷迭香酸对小鼠乙醇诱导的DNA损伤的保护作用。使用预先、共同和事后处理乙醇（5 g/kg）来测试迷迭香酸（100 mg/kg）的抗诱变能力。使用彗星试验评估外周血（1小时和24小时）和脑细胞（24小时），并使用微核试验分析骨髓（24小时）。结果与TBARS、具有抗氧化活性的酶和DCFH-DA试验的数据进行比较。外周血和脑细胞显示，与乙醇组相比，预先用迷迭香酸处理的乙醇组的平均损伤指数（DI）和损伤频率（DF）值显著降低。在脑细胞中，与乙醇组和阴性对照组相比，所有不同处理的乙醇和迷迭香酸均显著降低了DI和DF的平均值。各组之间微核频率、抗氧化酶活性和TBARS没有显著差异。DCFH-DA试验显示，与乙醇组相比，荧光强度降低了18%。结果表明，迷迭香酸可能降低乙醇诱导的DNA损伤水平，适用于这两种组织和处理周期。

The aim of the present work was to study the protective effects of rosmarinic acid against ethanol-induced DNA damage in mice. The antigenotoxic capacity of rosmarinic acid (100 mg/kg) was tested using pre-, co- and post-treatment with ethanol (5 g/kg). Peripheral blood (1 and 24 hr) and brain cells (24 hr) were evaluated using the comet assay and bone marrow was analyzed using the micronucleus assay (24 hr). The results were compared to data of TBARS, enzymes with antioxidant activity, and DCFH-DA test. Peripheral blood and brain cells show that mean damage index (DI) and damage frequency (DF) values of ethanol with pre-treatment with rosmarinic acid group were significantly lower than in the ethanol group. In brain cells all different treatments with ethanol and rosmarinic acid showed significant decrease in DI and DF mean values when compared to ethanol group and negative control. No significant differences were observed in micronucleus frequency, activity of antioxidant enzymes and TBARS between groups. The DCFH-DA test show a reduction of 18% of fluorescence intensity when compare with ethanol group. The results show that rosmarinic acid could decrease the levels of DNA damage induced by ethanol, for both tissues and treatment periods.

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)

吸收、分配和排泄

本研究的目的是在健康人体内确定迷迭香酸（RA）在一次摄入紫苏提取物（PE）后的吸收、代谢和尿液排泄情况。共有六名健康男性（平均年龄37.2 ± 6.2岁，平均体重指数22.0 ± 1.9 kg/m²）参加了这项交叉设计的研究，他们在摄入含有200毫克RA的PE和安慰剂之间有10天的间隔。在摄入前和指定的时间间隔收集血液样本，而尿液样本则是在摄入后0-6小时、6-24小时和24-48小时期间收集。通过LC-MS测量血浆和尿液中RA及其相关代谢物。摄入PE后，在尿液中检测到RA、甲基化RA（甲基-RA）、咖啡酸（CAA）、阿魏酸（FA）和微量的香豆酸（COA）。在血浆中，检测到RA、甲基-RA和FA，分别在摄入PE后的0.5小时、2小时和0.5小时达到最大水平。血浆和尿液中这些成分的绝大多数以结合形式（葡萄糖醛酸苷和/或硫酸盐）存在。RA及其相关代谢物在尿液中的排泄比例为总剂量的6.3 ± 2.2%，约75%的这些成分在摄入PE后6小时内被排泄。

The aim of this study in healthy humans was to determine the absorption, metabolism, and urinary excretion of rosmarinic acid (RA) after a single intake of perilla extract (PE). Six healthy men (mean age 37.2 +/- 6.2 y and mean body mass index 22.0 +/- 1.9 kg/sq m) were enrolled in the study that was a crossover design involving single intakes of PE containing 200 mg RA and placebo with a 10 day interval between treatments. Blood samples were collected before intake and at designated time intervals, while urine samples were collected over the periods 0-6 hr, 6-24 hr and 24-48 hr after intake. RA and its related metabolites in plasma and urine were measured by LC-MS. RA, methylated RA (methyl-RA), caffeic acid (CAA), ferulic acid (FA) and a trace of m-coumaric acid (COA) were detected in the urine after intake of PE. In plasma, RA, methyl-RA and FA were detected, with maximum levels obtained 0.5, 2 and 0.5 hr after intake of PE, respectively. The majority of these components in both plasma and urine were present as conjugated forms (glucuronide and/or sulfated). The proportion of RA and its related metabolites excreted in the urine was 6.3 +/- 2.2% of the total dose, with approximately 75% of these components being excreted within 6 hr after intake of PE.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

迷迭香酸能很好地从胃肠道和皮肤吸收。

Rosmarinic acid is well absorbed from gastrointestinal tract and from the skin.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

研究的目的是为了调查迷迭香酸（RA）的经皮吸收、组织分布和绝对生物利用度。在体外实验中，RA从醇溶液穿过切除的大鼠皮肤的透过率是从水中透过的大约8倍，这表明乙醇可能作为吸附促进剂。从水或醇溶液的流量分别是4.4或10微克/平方厘米/小时，而达到平衡的时间（tleg）分别是7.8或3.7小时。静脉给药后，RA最好用两室开放模型来描述；半衰期（t1/2）为1.8小时，分布相半衰期（t1/2 alpha）为0.07小时，中央室分布容积（V tau）为2.3升/千克，周边室分布容积（V beta）为15.3升/千克。当以W/O乳膏形式（25毫克/千克，50平方厘米）局部给药时，RA的绝对生物利用度为60%。静脉给药后0.5小时，在大脑、心脏、肝脏、肺、肌肉、脾脏和骨骼组织中检测到并测量到RA，其中肺组织中的浓度最高（是血液浓度的13倍），其次是脾脏、心脏和肝脏组织。局部给药大约3毫克，在20平方厘米的后腿上，4.5小时（峰值时间）后，在血液、皮肤、肌肉和骨骼组织中测量到RA。

The purpose of the study was to investigate the transdermal absorption of rosmarinic acid (RA), its tissue distribution and absolute bioavailability. In ex vivo experiments, permeation of RA across excised rat skin was about 8 times higher from alcoholic solution than from water, indicating that ethanol may act as sorption promoter. The flux from water or alcoholic solution was 4.4 or 10 ug/sq cm/hr, and the tleg was 7.8 or 3.7 hr, respectively. After I.V. administration, RA is best described by a 2-compartment open model; t1/2 = 1.8 hr, t1/2 alpha = 0.07 hr, V tau = 2.3 L/kg, V beta = 15.3 L/kg. Upon topical administration of RA in form of a W/O ointment (25 mg/kg, 50 sq cm), the absolute bioavailability was 60%. 0.5 hours after iv administration, RA was detected and measured in brain, heart, liver, lung, muscle, spleen and bone tissue, showing the highest concentration in lung tissue (13 times the blood concentration), followed by spleen, heart and liver tissue. 4.5 hours (peak time) after topical administration of about 3 mg on the hind leg over 20 sq cm, RA was measured in blood, skin, muscle and bone tissue.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  甲醇 、 (2S)-3-(3,4-dihydroxyphenyl)-2-{[(2E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy}propanoic acid 在 sulfonic resin Amberlite IR-120H 作用下， 反应 48.0h， 生成 methyl rosmarinate
  参考文献：
  名称：

  Relationship between Hydrophobicity and Antioxidant Ability of “Phenolipids” in Emulsion: A Parabolic Effect of the Chain Length of Rosmarinate Esters

  摘要：

  The polar paradox predicts that hydrophobic antioxidants are more active in emulsions than their hydrophilic homologues, thus assuming a linear dependency between hydrophobicity and antioxidant capacity. In contrast, we formulate in this paper an alternative hypothesis assuming a possible nonlinear dependency. To verify this so-called "nonlinear hypothesis", the antioxidant capacity of a homologous series of rosmarinic acid and its alkyl esters (methyl, butyl, octyl, dodecyl, hexadecyl, octadecyl, and eicosyl) was evaluated using a newly developed conjugated autoxidizable triene (CAT) assay. It appeared that the antioxidant capacity increases as the alkyl chain is lengthened, with a maximum for the octyl chain, after which further chain extension leads to a collapse in antioxidant capacity, This nonlinear effect was discussed in relation to the "cutoff effect" generally observed in studies using cultured cells. This new hypothesis may provide a better understanding of the antioxidant behavior of phenolics in emulsion which is a key to develop new antioxidant strategies to protect lipid substrates from oxidation. Moreover, the lipophilization with medium chain appeared as a promising way to enhance the antioxidant capacity of phenolics since octyl rosmarinate was three times more effective than rosmarinic acid which is already one of the most powerful known phenolic antioxidant. Finally, this work paves the way for systematic investigation of the chain length effect to design new "phenolipids" in a rational fashion.

  DOI：

  10.1021/jf904119v
• 作为产物：
  描述：

  2-氨基-3-(3-乙酰基-4-羟基苯基)丙酸 在 sodium hydroxide 、 Wilkinson's catalyst 、 水 、 双氧水 、 potassium carbonate 、 三乙胺 、 sodium nitrite 作用下， 以 乙醇 、 二氯甲烷 、 丙酮 、 苯 为溶剂， 反应 68.5h， 生成 (2S)-3-(3,4-dihydroxyphenyl)-2-{[(2E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy}propanoic acid
  参考文献：
  名称：

  (S)-(-)-迷迭香酸的非酶法合成和对(+)-rabdosiin的仿生途径的研究

  摘要：

  描述了以 9% 总产率合成 (S)-(-)-迷迭香酸 (30)。该合成是通过收敛途径实现的，其中 3-(3',4'-二羟基苯基)-(S)-乳酸 (23) 和咖啡酸 (25)，两者均得到适当保护，偶联产生五烯丙基前体 29 ，然后将其脱保护以得到 (S)-(-)-迷迭香酸 (30)。类似地制备了三烯丙基衍生物 35，并通过仿生氧化自由基偶联-环化，然后去烯丙基化转化为 (+)-rabdosiin (41) 及其 (1R,2S) 异构体 (42)。偶联-环化产生了不同于自然界中发现的 rabdosiin 非对映异构体的比例。初步研究表明，(R)-扁桃酸甲酯 (15) 可以非对映选择性地二聚化，得到 1,2-反式 thomasidioate 二酯 (16)。关键词：rabdosiin，迷迭香酸，木脂素，

  DOI：

  10.1139/v97-612

文献信息

• FMO3 inhibitors for treating pain
  申请人：Akron Molecules GmbH

  公开号：EP2674161A1

  公开（公告）日：2013-12-18

  The present invention relates to new therapies to treat pain and related diseases, as well as pharmaceutical compounds for use in said therapies.

  本发明涉及治疗疼痛和相关疾病的新疗法，以及用于上述疗法的药物化合物。
• USE OF ROSMARINIC ACID AND DERIVATIVES THEREOF AS AN IMMUNOSUPPRESSANT OR AN INHIBITOR OF SH2-MEDIATED PROCESS
  申请人：Mogam Biotechnology Research Institute

  公开号：EP1077715B1

  公开（公告）日：2006-03-29
• The first isolation of lignans, megacerotonic acid and anthocerotonic acid, from non-vascular plants, anthocerotae (hornworts)
  作者：Reiji Takeda、Jiro Hasegawa、Masateru Shinozaki

  DOI：10.1016/s0040-4039(00)97569-5

  日期：1990.1
• Compounds and Methods for Treating Pain
  申请人：Penninger Josef

  公开号：US20130252924A1

  公开（公告）日：2013-09-26

  The present invention relates to new therapies to treat pain and related diseases, as well as pharmaceutical compounds for use in said therapies.
• COMPOUNDS AND METHODS FOR TREATING PAIN
  申请人：AKRON MOLECULES AG

  公开号：US20140349969A1

  公开（公告）日：2014-11-27

  The present invention relates to new therapies to treat pain and related diseases, as well as pharmaceutical compounds for use in said therapies.