clavulanic acid | 62319-53-3

• 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
• 英文名称: clavulanic acid
• 英文别名: clavunalic acid；clavulanate；(5R)-3-((E)-2-hydroxy-ethylidene)-7-oxo-(5rH)-4-oxa-1-aza-bicyclo[3.2.0]heptane-2c-carboxylic acid；Iso-clavuaninsaeure；isoclavulanic acid；(2R,3E,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
• CAS: 62319-53-3
• 化学式: C₈H₉NO₅
• 分子量: 199.163
• InChiKey: HZZVJAQRINQKSD-INJCQMSSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  87.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  clavulanic acid 生成 (5R)-3t-methoxy-7-oxo-3c-vinyl-(5rH)-4-oxa-1-aza-bicyclo[3.2.0]heptane-2c-carboxylic acid benzyl ester
  参考文献：
  名称：

  从7-氧代-3-乙烯基-4-氧代-1-氮杂双环[3.2.0]庚烷全合成克拉维酸类似物

  摘要：

  通过亚硒酸酯消除方法，或利用新型的3-乙烯基丝氨酸衍生物，将3-乙烯基基团引入7-氧代-4-氧杂-1-氮杂-1-氮杂双环[3.2.0]庚烷环系统中证实了对烷氧基亚乙基的保护性。

  DOI：

  10.1039/c39780000439
• 作为产物：
  描述：

  clavaminic acid 在 cell-free Streptomyces clavuligerus ATCC 27064 mycelium 、 磷酸吡哆醛 、 丙酮酸 、 还原型辅酶II(NADPH)四钠盐 作用下， 以0.3%的产率得到clavulanic acid
  参考文献：
  名称：

  克拉维酸和普拉维胺酸在克拉维酸生物合成中的作用

  摘要：

  发现从饲喂有13 C-克拉维酸或13 C-普鲁帕米酸的克拉维链霉菌ATCC 27064的发酵中分离出的克拉维酸样品已正确标记，表明标题化合物是克拉维酸的生物合成前体。

  DOI：

  10.1039/c39870001739

文献信息

• HIGH PENETRATION PRODRUG COMPOSITIONS OF ANTIMICROBIALS AND ANTIMICROBIAL-RELATED COMPOUNDS
  申请人：Yu Chongxi

  公开号：US20100040548A1

  公开（公告）日：2010-02-18

  The invention provides compositions of novel high penetration compositions (HPC) or high penetration prodrugs (HPP) of antimicrobials and antimicrobial-related compounds, which are capable of crossing biological barriers with high penetration efficiency. The HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

  该发明提供了一种新型高渗透性复合物（HPC）或高渗透性前药（HPP）的组合物，包括抗微生物和抗微生物相关化合物，这些化合物能够以高渗透效率穿越生物屏障。HPP能够在穿越生物屏障后转化为母药活性药物或药物代谢物，从而可以治疗母药或代谢物所能治疗的疾病。此外，HPP能够到达母药可能无法进入或在目标区域获得足够浓度的区域，从而提供新的治疗方法。HPP可以通过各种给药途径向受试者施用，例如，局部给药到病情作用部位以高浓度，或者系统给药到生物体内并以更快速度进入全身循环。
• Inclusion complexes of clavulanic acid and of alkali salts thereof with beta-cyclodextrines
  申请人：LEK, tovarna farmacevtskih in kemicnih izdelkov, d.d.

  公开号：EP0578231A1

  公开（公告）日：1994-01-12

  Described is a new process for the preparation of alkali clavulanate from an aqueous solution of crude clavulanic acid, which is obtained in a conventional manner after the fermentation with a clavulanic-acid-producing microorganism, extracted with an ethyl acetate solution of a hydrophobic β-CD derivative such as heptakis-(2,3,6-tri-O-acetyl)-β-CD in at least equimolar ratio with regard to clavulanic acid. The resulting novel inclusion complexes of clavulanic acid and hydrophobic β-CD derivative in a molar ratio about 1:1 are isolated, purified and then converted with an alkali base or alkali alkanoate to the desired alkali clavulanate, which is isolated. Furthermore, there are described new inclusion complexes of clavulanic acid and of its pharmaceutically acceptable alkali salts both with hydrophilic β-CD derivatives and with hydrophobic β-CD derivatives, processes for the preparation thereof and the use thereof for the preparation of galenic forms with immediate as well as with sustained action, in combination with amoxicillin trihydrate, which are valuable medicaments in the therapy of infectious diseases.

  本发明描述了一种制备克拉维酸碱的新工艺，其原料为粗克拉维酸的水溶液，该水溶液是在用产克拉维酸的微生物发酵后以传统方法获得的，并用疏水性β-CD衍生物（如庚基-(2,3,6-三-O-乙酰基)-β-CD）的乙酸乙酯溶液提取，其与克拉维酸的比例至少为等摩尔。所得到的克拉维酸与疏水性β-CD衍生物摩尔比约为1:1的新型包合物经分离、纯化后，用碱或碱酸钾转化为所需的克拉维酸碱，并分离出来。此外，还描述了克拉维酸及其药学上可接受的碱盐与亲水性 β-CD 衍生物和疏水性 β-CD 衍生物的新包合物复合物、其制备过程以及将其用于制备具有速效和持续作用的 galenic 形式，与三水阿莫西林结合使用，是治疗传染病的重要药物。
• High penetration prodrug compositions of antimicrobials and antimicrobial-related compounds
  申请人：Yu Chongxi

  公开号：US10233197B2

  公开（公告）日：2019-03-19

  The invention provides compositions of novel high penetration compositions (HPC) or high penetration prodrugs (HPP) of antimicrobials and antimicrobial-related compounds, which are capable of crossing biological barriers with high penetration efficiency. The HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

  本发明提供了新型抗菌剂和抗菌剂相关化合物的高渗透组合物（HPC）或高渗透原药（HPP），它们能够以高渗透效率穿过生物屏障。HPPs 在穿过生物屏障后能够转化为母体活性药物或药物代谢物，因此能够提供母体药物或代谢物所能提供的治疗条件。此外，HPPs 还能到达母体药物可能无法到达的区域，或在目标区域产生足够的浓度，从而提供新的治疗方法。HPPs 可通过各种给药途径给药，例如，以高浓度局部给药到疾病的作用部位，或系统地给药到生物体内，以更快的速度进入血液循环。
• Novel process for the isolation of clavulanic acid and of pharmaceutically acceptable salts thereof
  申请人：——

  公开号：US20010007761A1

  公开（公告）日：2001-07-12

  A process for the isolation of clavulanic acid and pharmaceutically acceptable salts thereof, such as potassium clavulanate, from the aqueous fermentation broth of a clavulanic acid-producing microorganism comprises the microfiltration of the broth without prior treatment.

  从产生克拉维酸的微生物的含水发酵液中分离克拉维酸及其药学上可接受的盐类（如克拉维酸钾）的工艺包括对发酵液进行微过滤，而无需事先处理。
• Process
  申请人：——

  公开号：US20040063930A1

  公开（公告）日：2004-04-01

  A novel process for the removal of impurities from clavulanic acid using a selective adsorption material, in particular a molecularly imprinted polymer. Novel selective adsorption materials suitable for the process, and a process for the preparation of such selective adsorption materials, are also disclosed.

  一种利用选择性吸附材料，特别是分子印迹聚合物去除克拉维酸中杂质的新工艺。还公开了适用于该工艺的新型选择性吸附材料，以及制备这种选择性吸附材料的工艺。