tetra(L-lactic acid) | 151121-41-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: tetra(L-lactic acid)
• 英文别名: lactic acid tetramer；(2S)-2-[(2S)-2-[(2S)-2-[(2S)-2-hydroxypropanoyl]oxypropanoyl]oxypropanoyl]oxypropanoic acid
• CAS: 151121-41-4
• 化学式: C₁₂H₁₈O₉
• 分子量: 306.27
• InChiKey: CWKPYPSADSVGOA-XAMCCFCMSA-N

物化性质

• 沸点：
  457.7±35.0 °C(Predicted)
• 密度：
  1.327±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  21
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  136
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  naproxen chloride 、 tetra(L-lactic acid) 在 TEA 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成 naproxen-tetra(L-lactic acid)
  参考文献：
  名称：

  Low-molecular-weight proteins as carriers for renal drug targeting. Preparation of drug-protein conjugates and drug-spacer derivatives and their catabolism in renal cortex homogenates and lysosomal lysates

  摘要：

  Low molecular weight proteins (LMWPs) are known to be reabsorbed and catabolized primarily by the proximal tubular cells of the kidneys. As such, LMWPs might serve as drug carriers that release drugs site-specifically in the kidney. We tested this concept in vitro by coupling different drugs to the LMWP lysozyme both directly (amide bond) and via different spacers: oligopeptides (amide bond), (poly-)alpha-hydroxy acids (ester bond), and a pH sensitive cis-aconityl spacer (amide bond). The capability of the kidney to release the parent drug from such drug-spacer derivatives and drug-LMWP conjugates by enzymatic or chemical hydrolysis of the bond was tested by incubation experiments in renal cortex homogenates and lysosomal lysates. Directly coupled conjugates of terminal carboxyl group containing drugs and lysozyme were catabolized to single amino acids, but did not result in release of the parent drug. The amide bond between the drug and the final amino acid (lysine) appeared to be stable in the incubation milieu. Different oligopeptide spacers coupled to the drugs showed similar results: the oligopeptide itself was cleaved but the amide bond between the drug and different single amino acids remained untouched. Only amide bonds of derivatives of carboxylic drugs with peptide structures themselves were cleaved. Some of the directly coupled conjugates of terminal amino drugs and oligopeptides showed clear release of the parent drug whereas others were stable. Terminal amino drugs were rapidly released from an acid-sensitive cis-aconityl spacer. Terminal carboxyl group containing drugs were enzymatically released from their glycolic and lactic ester spacers at different rates. These kinds of drugs were also released as parent drug from LMWP conjugates with ester spacers like L-lactic acid. Increasing spacer length by intercalating a tetra(L-lactic acid) molecule between the drug and the protein further increased the extent and rate of drug release, indicating increased accessability of the bond to the enzymes. Terminal amino group containing drugs were rapidly generated as parent drug from LMWP conjugates using an acid-sensitive spacer. In addition the conjugates were found to be adequately stable in plasma, considering their rapid clearance from the bloodstream. It is concluded that LMWPs may indeed be of use as carriers for specific renal delivery of drugs, since renal cortex homogenates and lysosomal lysates are able to catabolize the protein and generate the parent drug from drug-LMWP conjugates bearing suitable spacers. The option of enzymatic release is limited by the narrow specificity of the lysosomal enzymes. This has profound implications for the synthesis of suitable conjugates, since the nature of the drug itself, the type of bond, and also spacer length largely determine whether release of the parent drug will occur. Tailor-made spacers containing the correct mode of attachment and the right spacer length are required for this option. Chemical hydrolysis, using acid-sensitive linkers, is suggested as a viable alternative approach.

  DOI：

  10.1021/jm00085a012
• 作为产物：
  描述：

  L-丙交酯 在 咪唑 、 5%-palladium/activated carbon 、 三氟化硼乙醚 、 D(+)-10-樟脑磺酸 、 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 50.0h， 生成 tetra(L-lactic acid)
  参考文献：
  名称：

  疏水性多芳香腔在水中捕获的亲水性低聚乳酸

  摘要：

  由于有效的水合作用，与生物有关的亲水性分子很少与水中的疏水性化合物和表面相互作用。然而，本文我们报道通过配位驱动的自组装形成的聚芳族胶囊的疏水腔可以以较高的结合常数（高达K a = 3×10 5  m）包封亲水性低聚乳酸。-1）。X射线晶体学和ITC分析表明，不寻常的主客体行为是由CH-π和氢键相互作用引起的焓稳定作用引起的。所述多芳族腔稳定可水解的环状二（乳酸），并且即使在水中也优先从低聚（乳酸）的混合物中捕获四（乳酸）。

  DOI：

  10.1002/anie.201800432

文献信息

• Characterization of linear and cyclic polylactic acids and their solvolysis products by electrospray ionization mass spectrometry
  作者：Issey Osaka、Mikio Watanabe、Masashi Takama、Masahiro Murakami、Ryuichi Arakawa

  DOI：10.1002/jms.1110

  日期：2006.10

  Linear and cyclic polylactic acids (PLAs) were characterized using electrospray ionization mass spectrometry (ESI-MS) as part of our ongoing investigation of the hydrolysis mechanism of biodegradable polymers. The condensation oligomers of linear polylactic acid (LPLA) were synthesized by thermal dehydration of L-lactic acid. The trimer and tetramer base polymers of cyclic polylactic acid (CPLA) were obtained by cyclization reactions of lactic acid trimers and tetramers, respectively. In the ESI-MS/MS measurement, LPLA yielded three types of product ion series, while CPLA yielded only one type, from which the repeated units of CPLA were removed. The MS/MS spectrum of the NH4+ adduct ion for both cyclic and linear PLA showed loss of one ammonia molecule. The postsource decay (PSD) spectrum of CPLA by matrix-assisted laser desorption ionization (MALDI) mass spectrometry was similar to the ESI-MS/MS spectrum, while that of LPLA was different. In addition, the degradation of cyclic and linear PLAs by solvolysis was investigated. Solvolysis with anhydrous MeOH was quite feasible, but did not readily occur in the presence of even a small amount of water in the MeOH solvent. Copyright © 2006 John Wiley & Sons, Ltd.

  作为我们正在进行的生物可降解聚合物水解机制研究的一部分，使用电喷雾电离质谱 (ESI-MS) 对线性和环状聚乳酸 (PLA) 进行了表征。通过L-乳酸热脱水合成线性聚乳酸(LPLA)缩合低聚物。环状聚乳酸(CPLA)的三聚体和四聚体基础聚合物分别通过乳酸三聚体和四聚体的环化反应获得。在ESI-MS/MS测量中，LPLA产生三种类型的产物离子系列，而CPLA仅产生一种类型，其中CPLA的重复单元被去除。环状和线性 PLA 的 NH4+ 加合离子的 MS/MS 谱显示损失了一个氨分子。基质辅助激光解吸电离 (MALDI) 质谱法得到的 CPLA 的源后衰变 (PSD) 谱与 ESI-MS/MS 谱相似，而 LPLA 的谱则不同。此外，还研究了溶剂分解对环状和线性 PLA 的降解作用。用无水MeOH进行溶剂分解是相当可行的，但在MeOH溶剂中即使存在少量水也不容易发生。版权所有 © 2006 约翰·威利父子有限公司
• On the prebiotic potential of reduced oxidation state phosphorus: the H-phosphinate–pyruvate system
  作者：David E. Bryant、Katie E. R. Marriott、Stuart A. Macgregor、Colin Kilner、Matthew A. Pasek、Terence P. Kee

  DOI：10.1039/c002689a

  日期：——

  H-Phosphinic acid and pyruvic acid, both plausible prebiotic chemicals, react selectively in water to build structural complexity including amide bond formation under remarkably mild conditions and oxidative coupling of P(1) compounds to condensed pyrophosphorus compounds.

  H-膦酸和丙酮酸都是可行的益生元化学物质，它们在水中选择性地反应，以建立结构复杂性，包括在非常温和的条件下形成酰胺键，以及P（1）化合物与缩合的焦磷化合物的氧化偶联。
• EP1484311
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