N-叔丁氧羰基-D-丝氨酸异丙酯 | 1253690-13-9

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 丝氨酸类衍生物
• 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
• 中文名称: N-叔丁氧羰基-D-丝氨酸异丙酯
• 英文名称: isopropyl N-(tert-butoxycarbonyl)-L-serinate
• 英文别名: D-Ser-OiPr；(R)-Isopropyl 2-((tert-butoxycarbonyl)amino)-3-hydroxypropanoate；propan-2-yl (2R)-3-hydroxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
• CAS: 1253690-13-9
• 化学式: C₁₁H₂₁NO₅
• 分子量: 247.291
• InChiKey: QVURMCPIMAXTNA-MRVPVSSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 储存条件：
  存储条件：2-8°C，密封保存，干燥环境。

反应信息

• 作为反应物：
  描述：

  N-叔丁氧羰基-D-丝氨酸异丙酯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 isopropyl O-{(5S)-5-[(4-amino-2-oxopyrimidin-1(2H)-yl)-methyl]-2-oxido-1,4,2-dioxaphosphinan-2-yl}-D-serinate bis(trifluoroacetate)
  参考文献：
  名称：

  Serine Side Chain-Linked Peptidomimetic Conjugates of Cyclic HPMPC and HPMPA: Synthesis and Interaction with hPEPT1

  摘要：

  Cidofovir (HPMPC), a broad spectrum antiviral agent, cannot be administered orally due to ionization of its phosphonic acid group at physiological pH. One prodrug approach involves conversion to the cyclic form (cHPMPC, 1) and esterification by the side chain hydroxyl group of a peptidomimetic serine. Transport studies in a rat model have shown enhanced levels of total cidofovir species in the plasma after oral dosing with L-Val-L-Ser-OMe cHPMPC, 2a. To explore the possibility that 2a and its three do stereoisomers 2b-d undergo active transport mediated by the peptide-specific intestinal transporter PEPT1, we performed radiotracer uptake and electrophysiology experiments applying the two-electrode voltage clamp technique in Xenopus laevis oocytes overexpressing human PEPT1 (hPEPT1, SLC15A1). 2a-d did not induce inward currents, indicating that they are not transported, but the stereoisomers with an L-configuration at the N-terminal valine (2a and 2b) potently inhibited transport of the hPEPT1 substrate glycylsarcosine (Gly-Sar). A "reversed" dipeptide conjugate, L-Ser-L-Ala-OiPr cHPMPC (4), also did not exhibit detectable transport, but completely abolished the Gly-Sar signal, suggesting that affinity of the transporter for these prodrugs is not impaired by a proximate linkage to the drug in the N-terminal amino acid of the dipeptide. Single amino acid conjugates of cHPMPC (3a and 3b) or cHPMPA (5, 6a and 6b) were not transported and only weakly inhibited Gly-Sar transport. The known hPEPT1 prodrug substrate valacyclovir (7) and its L-Val-L-Val dipeptide analogue (8) were used to verify coupled transport by the oocyte model. The results indicate that the previously observed enhanced oral bioavailability of 2a relative to the parent drug is unlikely to be due to active transport by hPEPT1. Syntheses of the novel compounds 2b-d and 3-6 are described, including a convenient solid-phase method to prepare 5, 6a and 6b.

  DOI：

  10.1021/mp100186b
• 作为产物：
  描述：

  isopropyl D-serinate hydrochloride 、 二碳酸二叔丁酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 N-叔丁氧羰基-D-丝氨酸异丙酯
  参考文献：
  名称：

  用于治疗真菌传染病的双靶点 COX-2/CYP51 抑制剂的设计、合成和生物学评价

  摘要：

  研究提出了新型双靶点（COX-2/CYP51）抑制剂的设计，通过骨架筛选和组合途径构建了三个系列的化合物；合成并评估了它们的分子结构。大多数化合物表现出显着的抗真菌能力。其中，选择具有优异抗真菌和抗耐药真菌能力（MIC 50 , 0.125-2.0 μg/mL）的潜在化合物（ 10a-2 , 16b-3 ）进行后续机理研究。一方面，这些化合物可以通过抑制 CYP51 阻断麦角甾醇的生物合成途径，影响真菌细胞的内部生理功能，包括 ROS 水平的升高、ΔΨ m的异常。，以及凋亡状态的出现。另一方面，这些化合物还有效地表现出对COX-2的抑制能力，消除了感染部位的炎症反应，激活了机体的免疫功能。综上所述，本研究不仅提供了一种新的抗真菌药物设计途径，而且发现了优良的靶标化合物。

  DOI：

  10.1021/acs.jmedchem.2c00878

文献信息

• Construction and Evaluation of Novel Dual-function Antifungal Inhibitors and Covalent Organic Framework Carriers Based on the Infection Microenvironment
  作者：Yating Liu、Qingpeng Wang、Shuai Yu、Min Liu、Jun Han、Bin Sun

  DOI：10.1021/acs.jmedchem.3c01372

  日期：2023.10.12
• 10.1021/acs.jmedchem.4c00710
  作者：Yu, Shuai、He, Yan-Qin、Liu, Yating、Ji, Shilei、Wang, Yajing、Sun, Bin

  DOI：10.1021/acs.jmedchem.4c00710

  日期：——
• Serine Side Chain-Linked Peptidomimetic Conjugates of Cyclic HPMPC and HPMPA: Synthesis and Interaction with hPEPT1
  作者：Larryn W. Peterson、Monica Sala-Rabanal、Ivan S. Krylov、Michaela Serpi、Boris A. Kashemirov、Charles E. McKenna

  DOI：10.1021/mp100186b

  日期：2010.12.6

  Cidofovir (HPMPC), a broad spectrum antiviral agent, cannot be administered orally due to ionization of its phosphonic acid group at physiological pH. One prodrug approach involves conversion to the cyclic form (cHPMPC, 1) and esterification by the side chain hydroxyl group of a peptidomimetic serine. Transport studies in a rat model have shown enhanced levels of total cidofovir species in the plasma after oral dosing with L-Val-L-Ser-OMe cHPMPC, 2a. To explore the possibility that 2a and its three do stereoisomers 2b-d undergo active transport mediated by the peptide-specific intestinal transporter PEPT1, we performed radiotracer uptake and electrophysiology experiments applying the two-electrode voltage clamp technique in Xenopus laevis oocytes overexpressing human PEPT1 (hPEPT1, SLC15A1). 2a-d did not induce inward currents, indicating that they are not transported, but the stereoisomers with an L-configuration at the N-terminal valine (2a and 2b) potently inhibited transport of the hPEPT1 substrate glycylsarcosine (Gly-Sar). A "reversed" dipeptide conjugate, L-Ser-L-Ala-OiPr cHPMPC (4), also did not exhibit detectable transport, but completely abolished the Gly-Sar signal, suggesting that affinity of the transporter for these prodrugs is not impaired by a proximate linkage to the drug in the N-terminal amino acid of the dipeptide. Single amino acid conjugates of cHPMPC (3a and 3b) or cHPMPA (5, 6a and 6b) were not transported and only weakly inhibited Gly-Sar transport. The known hPEPT1 prodrug substrate valacyclovir (7) and its L-Val-L-Val dipeptide analogue (8) were used to verify coupled transport by the oocyte model. The results indicate that the previously observed enhanced oral bioavailability of 2a relative to the parent drug is unlikely to be due to active transport by hPEPT1. Syntheses of the novel compounds 2b-d and 3-6 are described, including a convenient solid-phase method to prepare 5, 6a and 6b.
• Design, Synthesis, and Biological Evaluation of Dual-Target COX-2/CYP51 Inhibitors for the Treatment of Fungal Infectious Diseases
  作者：Wenxia Liu、Yating Liu、Haiyan Fan、Min Liu、Jun Han、Yunfei An、Yue Dong、Bin Sun

  DOI：10.1021/acs.jmedchem.2c00878

  日期：2022.9.22

  The design of novel dual-target (COX-2/CYP51) inhibitors was proposed in the study, and three series of compounds were constructed though the pathway of skeleton screening and combination; their molecular structures were synthesized and evaluated. Most of the compounds exhibited significant antifungal ability. Among them, potential compounds (10a-2, 16b-3) with excellent antifungal and anti-drug-resistant

  研究提出了新型双靶点（COX-2/CYP51）抑制剂的设计，通过骨架筛选和组合途径构建了三个系列的化合物；合成并评估了它们的分子结构。大多数化合物表现出显着的抗真菌能力。其中，选择具有优异抗真菌和抗耐药真菌能力（MIC 50 , 0.125-2.0 μg/mL）的潜在化合物（ 10a-2 , 16b-3 ）进行后续机理研究。一方面，这些化合物可以通过抑制 CYP51 阻断麦角甾醇的生物合成途径，影响真菌细胞的内部生理功能，包括 ROS 水平的升高、ΔΨ m的异常。，以及凋亡状态的出现。另一方面，这些化合物还有效地表现出对COX-2的抑制能力，消除了感染部位的炎症反应，激活了机体的免疫功能。综上所述，本研究不仅提供了一种新的抗真菌药物设计途径，而且发现了优良的靶标化合物。