3'-O-(tert-butyldimethylsilyl)-4'-(hydroxymethyl)-thymidine | 139887-99-3

• 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: 3'-O-(tert-butyldimethylsilyl)-4'-(hydroxymethyl)-thymidine
• 英文别名: 3'-O-t-butyldimethylsilyl4'-hydroxymethylthymidine；3'-O-t-butyldimethylsilyl-4'-c-hydroxymethylthymidine；1-[(2R,4S)-4-[tert-butyl(dimethyl)silyl]oxy-5,5-bis(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 139887-99-3
• 化学式: C₁₇H₃₀N₂O₆Si
• 分子量: 386.521
• InChiKey: FJHHUZIOCDGZAK-QWHCGFSZSA-N

物化性质

• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.88
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3'-O-(tert-butyldimethylsilyl)-4'-(hydroxymethyl)-thymidine 在 吡啶 、 ammonium hydroxide 、 盐酸羟胺 、 sodium acetate 、 乙酸酐 、 二甲基亚砜 、 三乙胺 、 cesium fluoride 、 三氯乙酸酐 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 4'-Cyanothymidine
  参考文献：
  名称：

  Synthesis of 4′-cyanothymidine and analogs as potent inhibitors of HIV.

  摘要：

  4'-Cyanothymidine inhibits HIV in A301 (Alex) cells with an IC50 of 0.002-mu-M. The uridine and cytidine analogs show similar potencies.

  DOI：

  10.1016/s0040-4039(00)77667-2
• 作为产物：
  描述：

  3'-O-(叔丁基二甲基硅烷基)胸苷 在 水 、 sodium hydroxide 、 2-碘酰基苯甲酸 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 2.0h， 生成 3'-O-(tert-butyldimethylsilyl)-4'-(hydroxymethyl)-thymidine
  参考文献：
  名称：

  [EN] COMPOUNDS AND METHODS FOR TREATING DISEASE
  [FR] COMPOSÉS ET MÉTHODES POUR TRAITER UNE MALADIE

  摘要：

  The invention provides compounds, compositions and methods for treating medical disorders, such as cancer, an autoimmune disorder, and/or a neurological disorder, and inhibiting LINE1 reverse transcriptase and/or HERV-K reverse transcriptase using a compound according to Formula I or a pharmaceutically acceptable salt thereof, or a related compound provided herein.

  公开号：

  WO2023178133A1

文献信息

• Free radical chemistry of nucleosides and nucleotides. Ring opening of C4′-radicals
  作者：David Crich、Qingwei Yao

  DOI：10.1016/s0040-4020(97)10262-9

  日期：1998.1

  It is demonstrated that nucleotide C4′ radicals may be generated from a C4′-thiolester on treatment with tributyltin hydride. When the reaction is conducted in benzene at reflux the C4′ radical expels the C3′-phosphate group to give a radical cation. This species undergoes deprotonation to an allylic radical which suffers cleavage of the deoxyribose ring. Similar reactions are observed when the reaction

  已经证明，在用氢化三丁基锡处理时，可以从C4'-硫代酸酯产生核苷酸C4'基团。当反应在苯中在回流条件下进行时，C4'自由基将C3'-磷酸基团排出，得到自由基阳离子。该种类经历去质子化为烯丙基自由基，该烯丙基自由基遭受脱氧核糖环的裂解。当用三（三甲基甲硅烷基）硅烷代替锡烷进行反应时，观察到类似的反应。在甲醇苯中，自由基阳离子被甲醇捕获，得到一个新的C4'自由基，该自由基在开环之前被淬灭。根据C3'处的取代基所施加的构象，讨论了C4'自由基对开环的行为。
• Preparation of Thymidine-4'-C-carboxylic Acid and Its Derivatives
  作者：Hubert Hřebabecký、Antonín Holý

  DOI：10.1135/cccc19971128

  日期：——

  3',5'-Di-O-benzoyl-4'-C-hydroxymethylthymidine (3) was prepared in four steps from 3'-O-(tert-butyldimethylsilyl)-4'-C-hydroxymethylthymidine (1). Oxidation of 3 with pyridinium dichromate afforded 3',5'-di-O-benzoylthymidine-4'-C-carboxylic acid (4) which on debenzoylation gave free thymidine-4'-C-carboxylic acid, (3R,2S,5R)-3-hydroxy-2-hydroxymethyl-5-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)tetrahydrofuran-2-carboxylic acid, (5). Esterification of acid 5 with diazomethane afforded the methyl ester 6. Its isopropyl ester 7 was obtained by transesterification of the methyl ester 6. Reaction of ester 6 with ammonia and hydrazine led to the respective amide 8 and hydrazide 9. Upon reaction with 1,1'-carbonyldiimidazole, the protected acid 4 was converted into the corresponding imidazolide 11, which, without isolation, was treated with glycinamide, dimethylamine and aminoethanol to give aminocarbonylmethylamide 12a, N,N-dimethylamide 13a and hydroxyethylamide 14a, respectively. The free amides 12b, 13b and 14b were obtained by methanolysis of corresponding benzoates with methanolic sodium methoxide. Neither of the prepared compounds exhibited significant activity against HIV.

  3',5'-二-O-苯甲酰基-4'-C-羟甲基胸腺嘧啶(3)由3'-O-(tert-丁基二甲基硅基)-4'-C-羟甲基胸腺嘧啶(1)经过四步反应制备而成。用吡啶二酸铬将3氧化后得到3',5'-二-O-苯甲酰基胸腺嘧啶-4'-C-羧酸(4)，去除苯甲酰基后得到自由胸腺嘧啶-4'-C-羧酸，(3R,2S,5R)-3-羟基-2-羟甲基-5-(5-甲基-2,4-二氧代-1,2,3,4-四氢嘧啶-1-基)四氢呋喃-2-羧酸(5)。将酸5酯化后得到甲酯6，再通过甲酯6的转酯化反应得到异丙酯7。将酯6与氨和肼反应得到相应的酰胺8和肼酰化合物9。用1,1'-羰基二咪唑将保护的酸4转化为相应的咪唑酰胺11，然后与甘氨酰胺、二甲胺和氨乙醇反应，分别得到氨基羰甲基酰胺12a、N,N-二甲基酰胺13a和羟乙酰胺14a。通过用甲醇钠甲氧化物对相应的苯甲酸酯进行甲醇解得到自由酰胺12b、13b和14b。制备的任何一种化合物均未表现出对HIV的显著活性。
• Novel linear and branched oligodeoxynucleotide analogues containing 4′-c-(hydroxymethyl)thymidine
  作者：Henrik Thrane、Jef Fensholdt、Mathias Regner、Jesper Wengel

  DOI：10.1016/0040-4020(95)00606-9

  日期：1995.9

  4′-C-(Hydroxymethyl)thymidine has been incorporated into novel linear and branched oligodeoxynueleotide (ODN) analogues by use of the phosphoramidite synthons 4, 7 and 11. ODNs containing modification X (from amidite 4, unnatural 5′-hydroxy to 4′-C-hydroxymethyl backbone) displayed significantly decreased thermal stabilities towards complementary DNA compared to unmodified controls. On the contrary

  4'-C-（羟甲基）胸苷已经通过使用亚磷酰胺合成子的掺入新颖的线性和支化oligodeoxynueleotide（ODN）的类似物4，7和11。与未修饰的对照相比，含有修饰X的ODN （从酰胺4到非天然的5'-羟基至4' - C-羟甲基主链）显示出对互补DNA的热稳定性大大降低。相反，含有修饰Y的ODN （来自酰胺7，天然5'-羟基至3'-羟基主链）对互补DNA和RNA形成高度稳定的双链体。亚磷酰胺11包含两个二甲氧基三苯甲基保护基的分子被用于全自动合成支化的ODN类似物，该ODN类似物在源自分支点的三个分支中的两个分支中包含相同的序列（修饰Z）。与线性参照物（ODN R）相比，支链ODN S仅表现出适度降低的热稳定性（朝着互补线性DNA）。这证明了额外的4'- C-羟甲基官能团（在Y型修饰中）作为引入指向DNA：DNA双链体小沟的分子实体的连接点的多功能性。
• Synthesis of oligodeoxynucleotides containing 4′-C-(Hydroxymethyl)thymidine: Novel promising antisense molecules
  作者：Jef Fensholdt、Henrik Thrane、Jesper Wengel

  DOI：10.1016/0040-4039(95)00301-r

  日期：1995.4

  4′-C-(Hydroxymethyl)thymidine derivative 1 was transformed into phosphoramidite 7 which was used for incorporation of 4′-C-hydroxymethyl functionalized thymidine monomers once and twice into 17-mer oligodeoxynucleotides (ODNs). The novel modified ODNs exhibited excellent affinity towards complementary DNA and increased resistance towards 3′-exonucleolytic degradation compared to unmodified ODNs.

  将4'- C-（羟甲基）胸腺嘧啶衍生物1转化为亚磷酰胺7，其用于将4'- C-羟甲基官能化的胸苷单体一两次结合到17-聚寡脱氧核苷酸（ODN）中。与未修饰的ODN相比，新型修饰的ODN对互补DNA表现出优异的亲和力，并且对3'-核酸外切降解的抵抗力增强。
• 4′-Substituted nucleosides as inhibitors of HIV: an unusual oxetane derivative.
  作者：Counde O-Yang、Walter Kurz、Elsie M. Eugui、Mary Jane McRoberts、Julien P.H. Verheyden、Lilia J. Kurz、Keith A.M Walker

  DOI：10.1016/s0040-4039(00)77668-4

  日期：1992.1

  The fused oxetane derivative of thymidine 3a inhibits HIV replication in A301 (Alex) cells with remarkably low bone marrow toxicity.