riboflavin

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 蝶啶及其衍生物
• 英文名称: riboflavin
• 英文别名: Vitamin B2；riboflavine；7,8-dimethyl-10-ribityl-isoalloxazine；Riboflavin binding protein from chicken egg white；7,8-dimethyl-10-[(2R,3R,4S)-2,3,4,5-tetrahydroxypentyl]benzo[g]pteridine-2,4-dione
• 化学式: C₁₇H₂₀N₄O₆
• 分子量: 376.369
• InChiKey: AUNGANRZJHBGPY-MBNYWOFBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  155
• 氢给体数：
  5
• 氢受体数：
  7

ADMET

代谢

自由核黄素在小肠粘膜中被转化为单核苷酸黄素，后者在肝脏中转化为黄素腺嘌呤二核苷酸。

Free riboflavin is converted in the intestinal mucosa into flavin mononucleotide which is transformed into flavin adenine dinucleotide in the liver.

来源:Hazardous Substances Data Bank (HSDB)

代谢

核黄素的代谢是一个受到严格调控的过程，它依赖于个体的核黄素状态。核黄素在大多数组织细胞的细胞质中被转化为辅酶，但主要在小肠、肝脏、心脏和肾脏中转化。核黄素的代谢过程始于腺苷三磷酸（ATP）依赖性的磷酸化，将维生素转化为黄素单核苷酸（FMN）。催化这一转化的黄素激酶受到激素的控制。FMN然后可以与特定的apo酶结合，形成各种黄素蛋白；然而，大部分通过FAD合成酶转化为黄素腺嘌呤二核苷酸（FAD）。因此，FAD是身体组织中主要的黄素辅酶。FAD的产生受到产物抑制的调控，即过量的FAD会抑制其进一步的产生。

The metabolism of riboflavin is a tightly controlled process that depends on the riboflavin status of the individual. Riboflavin is converted to coenzymes within the cellular cytoplasm of most tissues but mainly in the small intestine, liver, heart, and kidney. The metabolism of riboflavin begins with the adenosine triphosphate (ATP)-dependent phosphorylation of the vitamin to flavin mononucleotide (FMN). Flavokinase, the catalyst for this conversion, is under hormonal control. FMN can then be complexed with specific apoenzymes to form a variety of flavoproteins; however, most is converted to flavin-adenine dinucleotide (FAD) by FAD synthetase. As a result, FAD is the predominant flavocoenzyme in body tissues. Production of FAD is controlled by product inhibition such that an excess of FAD inhibits its further production.

来源:Hazardous Substances Data Bank (HSDB)

代谢

一个核黄素分子的生物合成需要一分子GTP和两分子核酮糖5-磷酸作为底物。GTP通过一序列的脱氨、侧链还原和去磷酸化反应水解释放，转化为5-氨基-6-核糖基氨基-2,4(1H,3H)-嘧啶二酮。与从核酮糖5-磷酸获得的3,4-二羟基-2-丁酮4-磷酸的缩合导致6,7-二甲基-8-核糖基乳清酸。维生素生物合成的最后一步涉及6,7-二甲基-8-核糖基乳清酸的歧化，该反应由核黄素合成酶催化。这个在机制上不寻常的反应涉及两个相同底物分子之间四碳片段的转移。第二个产物，5-氨基-6-核糖基氨基-2,4(1H,3H)-嘧啶二酮，通过6,7-二甲基-8-核糖基乳清酸合酶在生物合成途径中回收。本文将回顾到2007年的核黄素合成酶和相关蛋白的结构和反应机制，并引用了122篇参考文献。

The biosynthesis of one riboflavin molecule requires one molecule of GTP and two molecules of ribulose 5-phosphate as substrates. GTP is hydrolytically opened, converted into 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione by a sequence of deamination, side chain reduction and dephosphorylation. Condensation with 3,4-dihydroxy-2-butanone 4-phosphate obtained from ribulose 5-phosphate leads to 6,7-dimethyl-8-ribityllumazine. The final step in the biosynthesis of the vitamin involves the dismutation of 6,7-dimethyl-8-ribityllumazine catalyzed by riboflavin synthase. The mechanistically unusual reaction involves the transfer of a four-carbon fragment between two identical substrate molecules. The second product, 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione, is recycled in the biosynthetic pathway by 6,7-dimethyl-8-ribityllumazine synthase. This article will review structures and reaction mechanisms of riboflavin synthases and related proteins up to 2007 and 122 references are cited.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 暴露途径

该物质可以通过摄入被身体吸收。

The substance can be absorbed into the body by ingestion.

来源:ILO-WHO International Chemical Safety Cards (ICSCs)

毒理性

• 吸入症状

咳嗽。喉咙痛。

Cough. Sore throat.

来源:ILO-WHO International Chemical Safety Cards (ICSCs)

毒理性

• 眼睛症状

红斑。疼痛。

Redness. Pain.

来源:ILO-WHO International Chemical Safety Cards (ICSCs)

毒理性

• 相互作用

核黄素与其他B族维生素，尤其是烟酸和维生素B6相互关联。烟酸需要核黄素才能从色氨酸中形成，而维生素B6也需要核黄素来转化为辅酶形式。这些相互关系目前认为不会影响对核黄素的需求。

Riboflavin interrelates with other B vitamins, notably niacin, which requires riboflavin for its formation from tryptophan, and vitamin B6, which also requires riboflavin for a conversion to a conenzyme form. These interrelationships are not known to affect the requirement for riboflavin.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

据报道，普鲁本辛溴盐影响核黄素的吸收速率和程度。预先给予普鲁本辛溴盐会延迟核黄素的吸收速率，但增加了总共吸收的量，可能是通过增加了核黄素在消化道吸收位点的停留时间。

The rate and extent of absorption of riboflavin are reportedly affected by propantheline bromide. Prior administration of propantheline bromide delayed the rate of absorption of riboflavin but increased the total amount absorbed, presumably by increasing the residence time of riboflavin at GI absorption sites.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

核黄素从上消化道很容易被吸收；然而，药物的吸收涉及主动转运机制，且消化道吸收的量受到药物与吸收发生的特定粘膜部位接触时间的限制。在吸收发生之前，核黄素5'-磷酸在消化道腔内迅速且几乎完全去磷酸化。当与食物一起服用时，核黄素的消化道吸收量增加，在患有肝炎、肝硬化、胆道阻塞的患者或接受丙磺舒治疗的患者中吸收量减少。

Riboflavin is readily absorbed from the upper GI tract; however, absorption of the drug involves active transport mechanisms and the extent of GI absorption is limited by the duration of contact of the drug with the specialized segment of mucosa where absorption occurs. Riboflavin 5-phosphate is rapidly and almost completely dephosphorylated in the GI lumen before absorption occurs. The extent of GI absorption of riboflavin is increased when the drug is administered with food and is decreased in patients with hepatitis, cirrhosis, biliary obstruction, or in those receiving probenecid.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

核黄素在小肠通过一个快速、可饱和的传输系统被主要吸收。一小部分在大肠被吸收。吸收速率与摄入量成正比，当核黄素与食物一起摄入并在胆盐的存在下时，吸收速率会增加。在低摄入水平时，核黄素的大部分通过主动或促进传输系统被吸收。在较高的摄入水平时，核黄素可以通过被动扩散被吸收。

Primary absorption of riboflavin occurs in the small intestine via a rapid, saturable transport system. A small amount is absorbed in the large intestine. The rate of absorption is proportional to intake, and it increases when riboflavin is ingested along with other foods and in the presence of bile salts. At low intake levels, most absorption of riboflavin occurs via an active or facilitated transport system. At higher levels of intake, riboflavin can be absorbed by passive diffusion.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在血浆中，大量的核黄素与其它蛋白质结合，主要是免疫球蛋白，用于运输。妊娠增加了可用于核黄素的载体蛋白的水平，这导致在胎盘的母体表面核黄素的吸收率更高。

In the plasma, a large portion of riboflavin associates with other proteins, mainly immunoglobulins, for transport. Pregnancy increases the level of carrier proteins available for riboflavin, which results in a higher rate of riboflavin uptake at the maternal surface of the placenta.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在胃中，胃酸化作用会从蛋白质中释放出大多数核黄素（维生素B2）的辅酶形式（黄素腺嘌呤二核苷酸（FAD）和黄素单核苷酸（FMN））。随后，非共价结合的辅酶在上消化道被非特异性焦磷酸酶和磷酸酶水解成核黄素。核黄素的主要吸收发生在近端小肠，通过一个快速、可饱和的传输系统。吸收速率与摄入量成正比，当核黄素与食物一起摄入并存在胆盐时，吸收速率会增加。少量的核黄素通过肠肝循环系统循环。在低摄入水平时，核黄素的大部分吸收是通过主动或促进运输系统完成的。

In the stomach, gastric acidification releases most of the coenzyme forms of riboflavin (flavin-adenine dinucleotide (FAD) and flavin mononucleotide (FMN)) from the protein. The noncovalently bound coenzymes are then hydrolyzed to riboflavin by nonspecific pyrophosphatases and phosphatases in the upper gut. Primary absorption of riboflavin occurs in the proximal small intestine via a rapid, saturable transport system. The rate of absorption is proportional to intake, and it increases when riboflavin is ingested along with other foods and in the presence of bile salts. A small amount of riboflavin circulates via the enterohepatic system. At low intake levels most absorption of riboflavin is via an active or facilitated transport system.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  riboflavin 在 sodium periodate 作用下， 以 水 为溶剂， 以73.37%的产率得到10-(2,2-dihydroxylethyl)-7,8-dimethylisoalloxazine
  参考文献：
  名称：

  核黄素衍生物抗分枝杆菌活性的合成与评价

  摘要：

  鉴于结核分枝杆菌中缺乏核黄素转运蛋白，核黄素生物合成途径是开发新型抗分枝杆菌药物的有希望的目标。在此，设计、合成和筛选了一系列核黄素衍生物的抗分枝杆菌和抗菌活性。化合物1a、1b、2a、3a和5a显示出显着的抗结核分枝杆菌活性，最小抑制浓度 (MIC 99 ) 范围为 6.25 至 25 μM。在本研究中，先导化合物5a的选择性指数为 10.7。化合物2a ,图 2b、2c、4c和4d对革兰氏阳性菌株显示出相对低至中等的抗菌活性（MIC = 100-200 μM）。值得注意的是，即使在 200 μM 浓度下，这些化合物也没有显示出对革兰氏阴性菌株的任何抑制作用。此外，具有代表性的黄素单核苷酸 (FMN) 核糖开关的分子对接和结合实验表明，核黄素类似物似乎通过 FMN 核糖开关介导的核黄素生物合成抑制表现出抗分枝杆菌活性。除了 FMN 核糖开关，参与黄素生物合成的黄素蛋白也可能是核黄素衍生物

  DOI：

  10.1016/j.bmcl.2021.128236
• 作为产物：
  描述：

  3,4-二甲基苯胺 在 盐酸 、 sodium cyanoborohydride 作用下， 以 甲醇 、 水 、 溶剂黄146 、 正丁醇 为溶剂， 反应 53.67h， 生成 riboflavin
  参考文献：
  名称：

  15 N和13 C富集的黄素单核苷酸辅酶同位异构体的位点选择性合成

  摘要：

  黄素单核苷酸（FMN）是参与关键细胞和生理过程的众多蛋白质的辅酶。同位素标记的黄素是通过各种技术（包括NMR，IR，拉曼和质谱法）研究黄素酶催化反应的结构和机制的强大工具。在这份报告中，我们描述了通过五步化学酶促合成方法，从易得的前体中制备富集15 N和13 C同位素的，富含15 N和13 C同位素的标记的FMN同位素，辅酶的异四恶嗪核心的吡嗪和嘧啶环。

  DOI：

  10.1021/acs.joc.6b00640
• 作为试剂：
  描述：

  6-甲基腺素 在 Selectfluor 、 riboflavin 作用下， 以 水 、 乙腈 为溶剂， 37.0 ℃ 、101.33 kPa 条件下， 反应 3.0h， 以71%的产率得到腺嘌呤
  参考文献：
  名称：

  Visible-light-mediated oxidative demethylation of N⁶-methyl adenines

  摘要：

  一种新颖的化学调控RNA表观遗传学的解决方案，通过生物相容的光催化在可见光照射下已经被描述。

  DOI：

  10.1039/c7cc05544g

文献信息

• THIOL-ENE CLICK CHEMISTRY FOR DRUG CONJUGATES
  申请人：SYSCHEM, INC.

  公开号：US20130323169A1

  公开（公告）日：2013-12-05

  The present invention relates to linker molecules that readily conjugate cellular recognition ligand at one end and drug payload at the other, and are useful in treating or preventing cancer, an autoimmune disease, an inflammatory condition, a central nervous system disorder or an infection. The linker inker molecules of the invention are represented by Formula I, II and III; Linker-Drug compounds represented by Formula IV, V and VI; and Ligand-Linker-Drug conjugates represented by Formula VII, VIII and IX:

  本发明涉及易于在一端结合细胞识别配体和在另一端结合药物载荷的连接分子，并且在治疗或预防癌症、自身免疫疾病、炎症症状、中枢神经系统紊乱或感染方面具有用处。该发明的连接分子由公式I、II和III表示；由公式IV、V和VI表示的连接-药物化合物；以及由公式VII、VIII和IX表示的配体-连接-药物共轭物。
• [EN] BIOACTIVE CONJUGATES FOR OLIGONUCLEOTIDE DELIVERY<br/>[FR] CONJUGUÉS BIOACTIFS POUR L'ADMINISTRATION D'OLIGONUCLÉOTIDES
  申请人：UNIV MASSACHUSETTS

  公开号：WO2017030973A1

  公开（公告）日：2017-02-23

  Provided herein are self-delivering oligonucleotides that are characterized by efficient RISC entry, minimum immune response and off-target effects, efficient cellular uptake without formulation, and efficient and specific tissue distribution.

  本文提供的自递送寡核苷酸具有高效的RISC进入、最小的免疫反应和非靶效应、无需配方的高效细胞摄取，以及高效和特异的组织分布。
• [EN] FLAVIN DERIVATIVES<br/>[FR] DÉRIVÉS DE LA FLAVINE
  申请人：BIORELIX PHARMACEUTICALS INC

  公开号：WO2010019208A1

  公开（公告）日：2010-02-18

  The present invention relates novel flavin derivatives and other flavin derivatives, their use and compositions for use as riboswitch ligands and/or anti-infectives. The invention also provides method of making novel flavin derivatives.

  本发明涉及新型黄素衍生物和其他黄素衍生物，它们的用途以及用作核糖开关配体和/或抗感染剂的组合物。该发明还提供了制备新型黄素衍生物的方法。
• [EN] QUINAZOLINE DERIVATIVES, COMPOSITIONS, AND USES RELATED THERETO<br/>[FR] DÉRIVÉS DE QUINAZOLINE, COMPOSITIONS ET UTILISATIONS ASSOCIÉES
  申请人：UNIV EMORY

  公开号：WO2013181135A1

  公开（公告）日：2013-12-05

  The disclosure relates to quinazoline derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to inhibitors of NADPH-oxidases (Nox enzymes) and/or myeloperoxidase.

  该披露涉及喹唑啉衍生物、组合物以及相关方法。在某些实施例中，该披露涉及NADPH-氧化酶（Nox酶）和/或髓过氧化物酶的抑制剂。
• [EN] COMPOUNDS COMPRISING CLEAVABLE LINKER AND USES THEREOF<br/>[FR] COMPOSÉS COMPRENANT UN LIEUR CLIVABLE ET LEURS UTILISATIONS
  申请人：INTOCELL INC

  公开号：WO2019008441A1

  公开（公告）日：2019-01-10

  Provided are a compound including a cleavable linker, a use thereof, and an intermediate compound for preparing the same, and more particularly, the compound including a cleavable linker of the present invention may include an active agent (for example, a drug, a toxin, a ligand, a probe for detection, etc.) having a specific function or activity, a SO2 functional group which is capable of selectively releasing the active agent, and a functional group which triggers a chemical reaction, a physicochemical reaction and/or a biological reaction by external stimulation, and may further include a ligand (for example, oligopeptide, polypeptide, antibody, etc.) having binding specificity for a desired target receptor.

  提供了一种包括可切割连接物的化合物，其用途，以及用于制备该化合物的中间体化合物，更具体地，本发明的包括可切割连接物的化合物可能包括具有特定功能或活性的活性剂（例如，药物，毒素，配体，用于检测的探针等），能够选择性释放活性剂的SO2官能团，以及通过外部刺激触发化学反应，物理化学反应和/或生物反应的官能团，并且还可以包括具有与所需靶受体结合特异性的配体（例如，寡肽，多肽，抗体等）。