1-[2-(Amino-methoxy-methyl)-4-hydroxy-5-hydroxymethyl-tetrahydro-thiophen-2-yl]-5-methyl-1H-pyrimidine-2,4-dione

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: 1-[2-(Amino-methoxy-methyl)-4-hydroxy-5-hydroxymethyl-tetrahydro-thiophen-2-yl]-5-methyl-1H-pyrimidine-2,4-dione
• 英文别名: methyl (2S,4S,5R)-4-hydroxy-5-(hydroxymethyl)-2-(5-methyl-2,4-dioxopyrimidin-1-yl)thiolane-2-carboximidate
• 化学式: C₁₂H₁₇N₃O₅S
• 分子量: 315.35
• InChiKey: CUQACCOQIGMBCW-SXMVTHIZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  148
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1,4-anhydro-2-deoxy-3,5-O-(1,1,3,3-tetraisopropyldisiloxan-1,3-diyl)-4-thio-D-erythro-pent-1-enitol 在 吡啶 、 苯磺酰胺 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 三乙基硼 、 盐酸羟胺 、 四丁基氟化铵 、 氨 、 氧气 、 三正丁基氢锡 、 乙酸酐 、 戴斯-马丁氧化剂 、 N,N-二异丙基乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 甲苯 、 乙腈 为溶剂， 反应 32.5h， 生成 1-[2-(Amino-methoxy-methyl)-4-hydroxy-5-hydroxymethyl-tetrahydro-thiophen-2-yl]-5-methyl-1H-pyrimidine-2,4-dione
  参考文献：
  名称：

  Synthesis and antiviral activities of 1′-carbon-substituted 4′-thiothymidines

  摘要：

  4-Thiofuranoid glycals substituted at the 1-position with methyl (5), (t-butyldimethylsilyloxy)methyl (7), and acetoxymethyl (8) groups were prepared from the 3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl) (TIPDS)-4-thiofuranoid glycal (3) by way of LDA-lithiation. N-Iodosuccimide-initiated electrophilic glycosidation between silylated thymine and these 1-carbon-substituted 4-thioglycals gave the respective beta-anomers (9, 10, and 13) stereo selectively. Tin radical-mediated removal of the T-iodine atom from these products provided the corresponding 1'-branched 4'-thiothymidine derivatives (11, 12, and 14) in good yields. The 1'-hydroxymethyl derivative (15) served as a precursor for the preparation of the formyl (16), cyanoethenyl (17), and cyano (19) derivatives. Among the deprotected 1'-branched 4'-thiothymidines (20-25), the 1'-methyl analogue 20 showed the most potent anti-HSV-1 activity, but it was much less active than the parent compound 4'-thiothymidine. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.07.057

文献信息

• Synthesis and antiviral activities of 1′-carbon-substituted 4′-thiothymidines
  作者：Kazuhiro Haraguchi、Haruhiko Takahashi、Hiromichi Tanaka、Hiroyuki Hayakawa、Noriyuki Ashida、Takao Nitanda、Masanori Baba

  DOI：10.1016/j.bmc.2004.07.057

  日期：2004.10

  4-Thiofuranoid glycals substituted at the 1-position with methyl (5), (t-butyldimethylsilyloxy)methyl (7), and acetoxymethyl (8) groups were prepared from the 3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl) (TIPDS)-4-thiofuranoid glycal (3) by way of LDA-lithiation. N-Iodosuccimide-initiated electrophilic glycosidation between silylated thymine and these 1-carbon-substituted 4-thioglycals gave the respective beta-anomers (9, 10, and 13) stereo selectively. Tin radical-mediated removal of the T-iodine atom from these products provided the corresponding 1'-branched 4'-thiothymidine derivatives (11, 12, and 14) in good yields. The 1'-hydroxymethyl derivative (15) served as a precursor for the preparation of the formyl (16), cyanoethenyl (17), and cyano (19) derivatives. Among the deprotected 1'-branched 4'-thiothymidines (20-25), the 1'-methyl analogue 20 showed the most potent anti-HSV-1 activity, but it was much less active than the parent compound 4'-thiothymidine. (C) 2004 Elsevier Ltd. All rights reserved.