1-(2,3-dideoxy-4-C-methyl-β-D-glycero-pentofuranosyl)thymine | 151989-83-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1-(2,3-dideoxy-4-C-methyl-β-D-glycero-pentofuranosyl)thymine
• 英文别名: 1-(2,3-dideoxy-4-methyl-β-D-glycero-pentafuranosyl)thymine；3'-deoxy-4'-C-methylthymidine；1-[(2R,5S)-5-(hydroxymethyl)-5-methyl-tetrahydrofuran-2-yl]-5-methyl-pyrimidine-2,4-dione；1-[(2R,5S)-5-(hydroxymethyl)-5-methyloxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 151989-83-2
• 化学式: C₁₁H₁₆N₂O₄
• 分子量: 240.259
• InChiKey: YEWUZKGIJTWQRI-KCJUWKMLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  甲氧基-三氟甲基苯 、 1-(2,3-dideoxy-4-C-methyl-β-D-glycero-pentofuranosyl)thymine 在 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以53%的产率得到1-[2,3-dideoxy-4-methyl-5-O-(3,3,3-trifluoro-2-methoxy-2-phenyl)-propanoyl-D-glycero-pentafuranosyl]thymine
  参考文献：
  名称：

  Asymmetric Synthesis of 4′-Methyl-2′,3′-dideoxynucleosides

  摘要：

  DOI：

  10.1080/07328319908044858
• 作为产物：
  描述：

  O,O-二(三甲基甲硅烷基)胸苷 在 sodium hydroxide 、 (叔丁基二甲基)乙炔 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 4.0h， 生成 1-(2,3-dideoxy-4-C-methyl-β-D-glycero-pentofuranosyl)thymine
  参考文献：
  名称：

  Asymmetric Synthesis of 4′-Methyl-2′,3′-dideoxynucleosides

  摘要：

  DOI：

  10.1080/07328319908044858

文献信息

• Synthesis of 1-(2,3-Dideoxy-4-C-methyl-β-D-glycero-pent-2-enofuranosyl)thymine, 1-(2,3-Dideoxy-4-C-methyl-β-D-glycero-pentofuranosyl)thymine and 1-(4-C-Azidomethyl-2-deoxy-β-D-threo-pentofuranosyl)thymine
  作者：Hubert Hřebabecký、Antonín Holý

  DOI：10.1135/cccc19931668

  日期：——

  Reaction of isopropylidene derivative I with thionyl chloride in hexamethylphosphoric triamide afforded chloro derivative II. Removal of the isopropylidene group in II by treatment with a cation-exchanging resin (H⁺ form) gave the free chloro nucleoside III. reduction of the chloro derivative II with tributylstannane and subsequent removal of the isopropylidene group yielded deoxy derivative V. This was protected with tert-butyldiphenylsilyl group and converted into the mesylate VII. Elimination of the mesyl group followed by desilylation gave 1-(2,3-dideoxy-4-C-methyl-β-D-glycero-pent-2-enofuranosyl)thymine (IX) which was hydrogenated to afford 1-(2,3-dideoxy-4-C-methyl-β-D-glycero-pentofuranosyl)thymine (X). 1-(1-C-Azidomethyl-2-deoxy-β-D-threo-pentofuranosyl)thymine (XIII) was prepared by mesylation of the isopropylidene derivative I, nucleophilic substitution of the mesyl group with azide and removal of the isopropylidene group.

  异丙基亚甲基衍生物I与氯化硫酰在六甲基膦酰胺中反应，生成氯代衍生物II。用阳离子交换树脂（H+形式）处理II中的异丙基亚甲基基团，得到游离氯代核苷III。用三丁基锡还原氯代衍生物II，并随后去除异丙基亚甲基基团，得到脱氧衍生物V。这个化合物被叔丁基二苯基硅基保护，并转化为甲磺酸盐VII。去除甲磺基，随后去除硅基，得到1-(2,3-二去氧-4-C-甲基-β-D-glycero-pent-2-enofuranosyl)胸腺嘧啶（IX），通过氢化反应得到1-(2,3-二去氧-4-C-甲基-β-D-glycero-pentofuranosyl)胸腺嘧啶（X）。通过异丙基亚甲基衍生物I的甲磺化，甲磺基的亲核取代反应以及去除异丙基亚甲基基团，制备出1-(1-C-Azidomethyl-2-deoxy-β-D-threo-pentofuranosyl)胸腺嘧啶（XIII）。
• Synthesis and Biological Evaluation of 4′-<i>C</i>-Methyl Nucleosides
  作者：Toshiaki Waga、Hiroshi Ohrui、Hiroshi Meguro

  DOI：10.1080/07328319608002385

  日期：1996.1

  A series of 2'-deoxy, 2',3'-unsaturated and 2',3'-dideoxynucleoside analogues, which have an additional methyl group at the 4'-position, have been synthesized. When evaluated for their inhibitory activity against HIV in MT-4 cell, 2'-deoxy-4'-C-methyl nucleosides exhibited potent activity.
• [EN] LINE-1 INHIBITORS AS COGNITIVE ENHANCERS<br/>[FR] INHIBITEURS DE LINE-1 UTILISÉS EN TANT QU'ACTIVATEURS COGNITIFS
  申请人：[en]TRANSPOSON THERAPEUTICS, INC.

  公开号：WO2022256625A1

  公开（公告）日：2022-12-08

  The present disclosure provides methods of enhancing cognition, inhibiting cognitive decline, treating or preventing a cognitive deficit disorder, or treating or preventing Creutzfeldt-Jakob disease (CJD) in a subject in need thereof comprising administering a LINE-1 inhibitor, or a pharmaceutical composition thereof, to the subject.
• Asymmetric Synthesis of 4′-Methyl-2′,3′-dideoxynucleosides
  作者：Frederick A. Luzzio、Alexander V. Mayorov、Michael E. Menes、William L. Champion

  DOI：10.1080/07328319908044858

  日期：1999.9