(3S,4R)-1-N-tert-butyloxycarbonyl-3-(4,4'-dimethoxytrityloxy)-4-hydroxypyrrolidine | 926913-17-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (3S,4R)-1-N-tert-butyloxycarbonyl-3-(4,4'-dimethoxytrityloxy)-4-hydroxypyrrolidine
• 英文别名: [3S,4R]-1-N-Boc-3-dimethoxytrityloxy-4-hydroxypyrrolidine；tert-butyl (3S,4R)-3-[bis(4-methoxyphenyl)-phenylmethoxy]-4-hydroxypyrrolidine-1-carboxylate
• CAS: 926913-17-9
• 化学式: C₃₀H₃₅NO₆
• 分子量: 505.611
• InChiKey: CVBNBHLLSHTNKI-SXOMAYOGSA-N

物化性质

• 沸点：
  618.9±55.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  77.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3S,4R)-1-N-tert-butyloxycarbonyl-3-(4,4'-dimethoxytrityloxy)-4-hydroxypyrrolidine 在 4-二甲氨基吡啶 、 caesium carbonate 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 97.0h， 生成 (3S,4S)-4-(adenin-9-yl)-1-N-tert-butyloxycarbonyl-3-(4,4'-dimethoxytrityloxy)pyrrolidine
  参考文献：
  名称：

  Synthesis of diastereomeric 3-hydroxy-4-pyrrolidinyl derivatives of nucleobases

  摘要：

  The work deals with the synthesis of hydroxypyrrolidine analogs of nucleosides. Starting from the optically pure L- or D-tartaric acid, we improved the synthesis of enantiomeric trans-3,4-dihydroxypyrrolidines and elaborated a procedure for the synthesis of all possible diastereoisomers of 3-hydroxy-4-pyrrolidinyl derivatives of both purine and pyrimidine nucleobases. The prepared compounds were tested for cytostatic and antiviral properties but no significant activity was found. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2006.11.047
• 作为产物：
  描述：

  [3S,4S]-1-N-Boc-3-dimethoxytrityloxy-4-hydroxypyrrolidine 在 2,6-二甲基吡啶 、 偶氮二甲酸二异丙酯 、 氨 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 4.0h， 生成 (3S,4R)-1-N-tert-butyloxycarbonyl-3-(4,4'-dimethoxytrityloxy)-4-hydroxypyrrolidine
  参考文献：
  名称：

  Synthesis of diastereomeric 3-hydroxy-4-pyrrolidinyl derivatives of nucleobases

  摘要：

  The work deals with the synthesis of hydroxypyrrolidine analogs of nucleosides. Starting from the optically pure L- or D-tartaric acid, we improved the synthesis of enantiomeric trans-3,4-dihydroxypyrrolidines and elaborated a procedure for the synthesis of all possible diastereoisomers of 3-hydroxy-4-pyrrolidinyl derivatives of both purine and pyrimidine nucleobases. The prepared compounds were tested for cytostatic and antiviral properties but no significant activity was found. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2006.11.047

文献信息

• [EN] 6-OXOPURINE PHOSPHORIBOSYL TRANSFERASE INHIBITORS<br/>[FR] INHIBITEURS DES 6-OXOPURINE PHOSPHORIBOSYLTRANSFÉRASES
  申请人：UNIV QUEENSLAND

  公开号：WO2017100849A1

  公开（公告）日：2017-06-22

  The invention relates to compounds which are useful as inhibitors of 6-oxopurine phosphoribosyltransferases such as hypoxanthine-guanine-(xanthine) phosphoribosyltransferase (HG(X)PRT).

  这项发明涉及作为6-氧杂嘌呤磷酸核糖转移酶抑制剂的化合物，例如次黄嘌呤-鸟嘌呤-(黄嘌呤)磷酸核糖转移酶（HG(X)PRT）。
• Design of <i>Plasmodium vivax</i> Hypoxanthine-Guanine Phosphoribosyltransferase Inhibitors as Potential Antimalarial Therapeutics
  作者：Dianne T. Keough、Dominik Rejman、Radek Pohl、Eva Zborníková、Dana Hocková、Tristan Croll、Michael D. Edstein、Geoff W. Birrell、Marina Chavchich、Lieve M. J. Naesens、Gregory K. Pierens、Ian M. Brereton、Luke W. Guddat

  DOI：10.1021/acschembio.7b00916

  日期：2018.1.19

  Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) are the foremost causative agents of malaria. Due to the development of resistance to current antimalarial medications, new drugs for this parasitic disease need to be discovered. The activity of hypoxanthine-guanine-[xanthine]phosphoribosyltransferase, HG[X]PRT, is reported to be essential for the growth of both of these parasites, making it an excellent target for antimalarial drug discovery. Here, we have used rational structure-based methods to design an inhibitor, [3R,4R]-4-guanin-9-yl-3-((S)-2-hydroxy-2-phosphonoethyl)oxy-1-N-(phosphonopropionyl)pyrrolidine, of PvHGPRT and PfHGXPRT that has K-i values of 8 and 7 nM, respectively, for these two enzymes. The crystal structure of PvHGPRT in complex with this compound has been determined to 2.85 angstrom resolution. The corresponding complex with human HGPRT was also obtained to allow a direct comparison of the binding modes of this compound with the two enzymes. The tetra-(ethyl L-phenylalanine) tetraamide prodrug of this compound was synthesized, and it has an IC50 of 11.7 +/- 3.2 mu M against Pf lines grown in culture and a CC50 in human A549 cell lines of 102 +/- 11 mu M, thus giving it a similar to 10-fold selectivity index.
• Radiolabeled Aminopyrazoles as Novel Isoform Selective Probes for pJNK3 Quantification
  作者：Brian C. Bales、Victoria Cotero、Dan E. Meyer、Jeannette C. Roberts、Monica Rodriguez-Silva、Tiberiu M. Siclovan、Jeremy W. Chambers、Michael J. Rishel

  DOI：10.1021/acsmedchemlett.2c00278

  日期：2022.10.13
• Synthesis of diastereomeric 3-hydroxy-4-pyrrolidinyl derivatives of nucleobases
  作者：Dominik Rejman、Petr Kočalka、Miloš Buděšínský、Radek Pohl、Ivan Rosenberg

  DOI：10.1016/j.tet.2006.11.047

  日期：2007.1

  The work deals with the synthesis of hydroxypyrrolidine analogs of nucleosides. Starting from the optically pure L- or D-tartaric acid, we improved the synthesis of enantiomeric trans-3,4-dihydroxypyrrolidines and elaborated a procedure for the synthesis of all possible diastereoisomers of 3-hydroxy-4-pyrrolidinyl derivatives of both purine and pyrimidine nucleobases. The prepared compounds were tested for cytostatic and antiviral properties but no significant activity was found. (c) 2006 Elsevier Ltd. All rights reserved.