methyl 1-acetyl-trans-4-hydroxy-L-proplinate | 67943-19-5

• 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: methyl 1-acetyl-trans-4-hydroxy-L-proplinate
• 英文别名: Methyl N-Acetyl-trans-4-hydroxy-L-prolinate；AcHypOMe；methyl (2S,4R)-1-acetyl-4-hydroxypyrrolidine-2-carboxylate；trans-1-acetyl-4-hydroxy-L-proline methyl ester；trans-1-Acetyl-4-hydroxy-L-prolin-methylester；(2S,4R)-methyl 1-acetyl-4-hydroxypyrrolidine-2-carboxylate
• CAS: 67943-19-5
• 化学式: C₈H₁₃NO₄
• 分子量: 187.196
• InChiKey: RRXCEVZGPPDCGR-RQJHMYQMSA-N

物化性质

• 熔点：
  78 °C
• 沸点：
  342.7±42.0 °C(Predicted)
• 密度：
  1.285±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 1-acetyl-trans-4-hydroxy-L-proplinate 在 吡啶 、 sodium hydroxide 作用下， 生成 cis-1-acetyl-4-hydroxy-DL-proline
  参考文献：
  名称：

  Neuberger, Journal of the Chemical Society, 1945, p. 431

  摘要：

  DOI：
• 作为产物：
  描述：

  L-羟基脯氨酸 在 甲醇 、 氯化亚砜 、 potassium carbonate 作用下， 生成 methyl 1-acetyl-trans-4-hydroxy-L-proplinate
  参考文献：
  名称：

  Two prolines with a difference: contrasting stereoelectronic effects of 4R/S-aminoproline on triplex stability in collagen peptides [Pro(X)-Pro(Y)-Gly]nElectronic supplementary information (ESI) available: 1H NMR spectra and coupling constant analysis of 3 and 4; synthetic schemes for 3, 4, 5 and 6; FABMS of 3 and 4; MALDI-TOF MS of 5 and 6; HPLC of peptides 5 and 6. See http://www.rsc.org/suppdata/cc/b3/b308581c/

  摘要：

  在胶原肽[pro(X)-pro(Y)-Gly]n中，当4R/S-氨基脯氨酸位于X位置时，对三重螺旋稳定性表现出pH和立体化学依赖性效应。

  DOI：

  10.1039/b308581c

文献信息

• TAU-PROTEIN TARGETING PROTACS AND ASSOCIATED METHODS OF USE
  申请人：Arvinas, Inc.

  公开号：US20180125821A1

  公开（公告）日：2018-05-10

  The present disclosure relates to bifunctional compounds, which find utility as modulators of tau protein. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a VHL or cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds tau protein, such that tau protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of tau. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of tau protein. Diseases or disorders that result from aggregation or accumulation of tau protein are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，其作为tau蛋白的调节剂具有实用性。具体而言，本公开涉及含有一端结合到E3泛素连接酶的VHL或cereblon配体，另一端结合到tau蛋白的双功能化合物，使得tau蛋白与泛素连接酶靠近，以实现tau蛋白的降解（和抑制）。本公开展示了与tau蛋白降解/抑制相关的广泛药理活性。本公开的化合物和组合物用于治疗或预防由tau蛋白聚集或积累导致的疾病或紊乱。
• HETEROCYCLIC ANTIVIRAL COMPOUNDS
  申请人：Chin Elbert

  公开号：US20100081658A1

  公开（公告）日：2010-04-01

  Compounds having the formula I wherein R 1 , R 2a , R 2b , R 2c , R 3 , Y and p are as defined herein and C2-C3 is a single or double bond are Hepatitis C virus NS5b polymerase inhibitors. Also disclosed are compositions and methods for treating an HCV infection and inhibiting HCV replication.

  具有以下公式的化合物 I，其中 R1、R2a、R2b、R2c、R3、Y 和 p 的定义如本文所述，且 C2-C3 是单键或双键的化合物是丙型肝炎病毒NS5b聚合酶抑制剂。还公开了用于治疗HCV感染和抑制HCV复制的组合物和方法。
• Methods for Production of Optically Active Fluoropyrrolidine Derivatives
  申请人：Umemoto Teruo

  公开号：US20100174096A1

  公开（公告）日：2010-07-08

  Useful industrial methods for producing optically active fluoropyrrolidine derivatives as useful fluorinated intermediates are disclosed.

  揭示了用于生产光学活性氟吡咯烷衍生物的有用工业方法，作为有用的氟化中间体。
• The Implications of (2<i>S</i>,4<i>S</i>)-Hydroxyproline 4-<i>O</i>-Glycosylation for Prolyl Amide Isomerization
  作者：Neil W. Owens、Adrian Lee、Kirk Marat、Frank Schweizer

  DOI：10.1002/chem.200900844

  日期：2009.10.12

  delineated by the proline side chain. The enthalpic contributions to the stabilization of the trans amide isomer may be due to disruption of intramolecular interactions present in hyp; the change in enthalpy is balanced by a decrease in entropy incurred upon glycosylation. Because the different stereoisomers—Hyp and hyp—project the O‐linked carbohydrates in opposite spatial orientations, these glycosylated

  肽和蛋白质的构象通常受与丝氨酸（Ser）或苏氨酸（Thr）连接的聚糖O的影响。（2 S，4 R）‐4‐脯氨酸（Hyp）与L‐脯氨酸（Pro）一起是O‐糖基化的有趣目标，因为它们对肽和蛋白质构象有独特的影响。在以前的工作中，我们发现Hyp的糖基化作用不会影响模型酰胺中N末端酰胺的反式/顺式比（K反式/顺式）或酰胺异构化速率。Hyp-（2 S，4 S）-4-羟基脯氨酸（hyp）-在自然界中很少见，并且对吡咯烷环的构型和K反式/顺式具有不同的影响。附着在hyp上的聚糖预计会从脯氨酸侧链相对于hyp的相反面突出；这对K反式/顺式的影响尚不清楚。测量3个Ĵ偶合常数表明聚糖具有影响不大的C γ -内型构象由HYP制备。其结果是，人们发现，在d半乳糖残基从C延伸的γ -内切皱褶会同时影响ķ反式/顺式和异构化的速率，这是没有找到时，它选自C投影到发生γ -外型皱褶; 这反映了脯氨酸侧链所描绘的不同环境。焓
• Design, synthesis and preliminary evaluation of novel pyrrolidine derivatives as matrix metalloproteinase inhibitors
  作者：Xian-Chao Cheng、Qiang Wang、Hao Fang、Wei Tang、Wen-Fang Xu

  DOI：10.1016/j.ejmech.2007.12.020

  日期：2008.10

  of novel pyrrolidine derivatives were designed, synthesized and assayed for their inhibitory activities on matrix metalloproteinase 2 (MMP-2) and aminopeptidase N (AP-N). The results showed that these pyrrolidine derivatives exhibited highly selective inhibition against MMP-2 as compared with AP-N. The hydroxamates 8a-c were equally or more potent MMP-2 inhibitors than the positive control LY52. The

  设计，合成和测定了一系列新颖的吡咯烷衍生物对基质金属蛋白酶2（MMP-2）和氨基肽酶N（AP-N）的抑制活性。结果表明，与AP-N相比，这些吡咯烷衍生物表现出对MMP-2的高度选择性抑制。异羟肟酸酯8a-c是与阳性对照LY52同等或更有效的MMP-2抑制剂。提出了最有效的化合物8a与MMP-2的结合方式。构效关系也作了简要讨论。