1,4-anhydro-2-deoxy-3,5-O-(di-tert-butylsilylene)-4-thio-D-erythro-pento-1-enitol | 209048-62-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氢噻吩类
• 英文名称: 1,4-anhydro-2-deoxy-3,5-O-(di-tert-butylsilylene)-4-thio-D-erythro-pento-1-enitol
• 英文别名: 1,4-anhydro-2-deoxy-3,5-O-(di-tert-butylsilylene)-4-thio-D-erythro-pent-1-enitol；(4aR,7aS)-2,2-ditert-butyl-4a,7a-dihydro-4H-thieno[3,2-d][1,3,2]dioxasiline
• CAS: 209048-62-4
• 化学式: C₁₃H₂₄O₂SSi
• 分子量: 272.484
• InChiKey: VHKGJJQOPYVXTH-WDEREUQCSA-N

物化性质

• 熔点：
  68-69 °C
• 沸点：
  322.8±41.0 °C(Predicted)
• 密度：
  1.03±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.07
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  43.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,4-anhydro-2-deoxy-3,5-O-(di-tert-butylsilylene)-4-thio-D-erythro-pento-1-enitol 在 N-碘代丁二酰亚胺 、 1,5-二氮杂双环[4.3.0]壬-5-烯 、 四丁基氟化铵 、 lithium benzoate 、 苯甲酸 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 5.0h， 生成 4'-硫代尿苷
  参考文献：
  名称：

  立体选择性合成4'-硫代核苷的β-异头物，基于对4-硫呋喃类化合物糖基的亲电糖基化。

  摘要：

  制备了具有不同3,5-O-甲硅烷基保护基的三种类型的4-硫呋喃基糖，并对其亲电性进行了研究。3,5-双-O-（叔丁基二甲基甲硅烷基）-4-硫呋喃类化合物糖基（5）是通过将2-脱氧-4-硫代-D-赤型戊呋喃糖（4）进行甲磺酸化并随后进行碱促进的消除反应而获得的，热消除亚砜衍生物适用于制备3,5-O-（四异丙基二硅氧烷-1,3-二基）（9）和3,5-O-（二叔丁基亚甲硅烷基）（11）4-硫代缩醛。通过使用尿嘧啶，胸腺嘧啶，胞嘧啶和N（6）-苯甲酰腺嘌呤的甲硅烷基化衍生物，在PhSeCl或NIS存在下，进行这些4-硫代糖基的糖基化反应。在这三种4-硫代糖中，有11种是出色的糖基供体，

  DOI：

  10.1021/jo020037x
• 作为产物：
  描述：

  1,4-二脱氧-1,4-环硫-D-核糖醇 在 吡啶 、 咪唑 、 1,5-二氮杂双环[4.3.0]壬-5-烯 、 二叔丁基硅基双(三氟甲烷磺酸) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 1,4-anhydro-2-deoxy-3,5-O-(di-tert-butylsilylene)-4-thio-D-erythro-pento-1-enitol
  参考文献：
  名称：

  An Access to the β-Anomer of 4′-Thio-C-ribonucleosides: Hydroboration of 1-C-Aryl- or 1-C-Heteroaryl-4-thiofuranoid Glycals and Its Regiochemical Outcome

  摘要：

  We have developed a novel method for the synthesis of the beta-anomer of 4'-thio-C-ribonucleosides from 3,5-O-(di-tert-butylsilylene)-4-thiofuranoid glycal. Palladium-catalyzed coupling of 1-tributylstannyl-4-thiofuranoid glycal with iodobenzene or a heteroaryl halide gave 1-C-phenyl- or 1-C-heteroaryl-glycals. Hydroboration of these glycals proceeded at the alpha-face, and subsequent alkaline hydrogen peroxide treatment of the resulting 2'-alpha-borane furnished the respective beta-anomer of 4'-thio-C-ribonucleosides. These results demonstrate that this synthetic method has a wider scope in terms of heterocyclic base structure. During this study, unexpected Markovnikov-oriented hydroboration has been observed to lead to the respective 1'-alpha-boranes. These 1'-boranes were converted into either the ring-opened structure or the 2'-deoxy derivatives depending upon their stability.

  DOI：

  10.1021/jo201100n

文献信息

• [EN] RIBONUCLEIC ACIDs WITH 4'-THIO-MODIFIED NUCLEOTIDES AND RELATED METHODS<br/>[FR] ACIDES RIBONUCLÉIQUES AYANT DES NUCLÉOTIDES 4'-THIO-MODIFIÉS ET PROCÉDÉS ASSOCIÉS
  申请人：SHIRE HUMAN GENETIC THERAPIES

  公开号：WO2014152513A1

  公开（公告）日：2014-09-25

  Disclosed are messenger RNA molecules and related compositions incorporating a 4'-thio modification in the furanose ring of at least one nucleotide residue, and methods of using these mRNAs to produce an encoded therapeutic protein invivo and to treat or prevent diseases or disorders. In certain embodiments, the 4'-thio modified mRNA provides for enhanced stability and/or reduced immunogenicity in in vivo therapies.

  本文揭示了信使RNA分子及相关组合物，其中至少一个核苷酸残基的呋喃糖环中包含4'-硫代修饰，并且使用这些mRNA来在体内产生编码的治疗蛋白质并用于治疗或预防疾病或紊乱的方法。在某些实施例中，4'-硫代修饰的mRNA在体内疗法中提供了增强的稳定性和/或减少的免疫原性。
• Additive Pummerer Reaction of 3,5-<i>O</i>-(Di-<i>tert</i>-butyl)silylene-4-thiofuranoid Glycal: A High-Yield and β-Selective Entry to 4′-Thioribonucleosides
  作者：Kazuhiro Haraguchi、Hiromitsu Matsui、Shin Takami、Hiromichi Tanaka

  DOI：10.1021/jo802615h

  日期：2009.3.20

  Upon reacting 3,5-O-(di-tert-butyl)silylene-4-thiofuranoid glycal S-oxide (6) with Ac2O/TMSOAc/BF3 center dot OEt2 in CH2Cl2, the additive Pummerer reaction proceeded to furnish the corresponding 1,2-di-O-acetyl-4-thioribofuranose 7. Compound 7 serves as a highly beta-selective glycosyl donor in the Vorbruggen condensation carried out in the presence of TMSOTf. Thus, the 4-thio-beta-D-ribofuranosyl derivatives of uracil, thymine, N-4-acetylcytosine, 6-chloropurine, and 2-amino-6-chloropurine were synthesized. The use of 7 can be extended to the beta-selective synthesis of 4'-thio-C-ribonucleosides.
• Electrophilic addition to 4-thio furanoid glycal: a highly stereoselective entry to 2′-deoxy-4′-thio pyrimidine nucleosides
  作者：Kazuhiro Haraguchi、Ayako Nishikawa、Eiko Sasakura、Hiromichi Tanaka、Kazuo T. Nakamura、Tadashi Miyasaka

  DOI：10.1016/s0040-4039(98)00543-7

  日期：1998.5

  4-Thio furanoid glycals with different types of O-silyl protection have been prepared from benzyl 3,5-di-O-benzyl-2-deoxy-1,4-dithio-D-erythro-pentofuranoside. Face-selectivity for PhSeCl- or N-iodosuccimide-initiated addition of a pyrimidine base to the thioglycal was found to be controlled by O-silyl protecting groups. Using the thioglycal protected with a 3,5-O-di-t-butylsilyl group, a highly stereoselective synthesis of beta-2'-deoxy-4'-thio pyrimidine nucleosides has been accomplished. (C) 1998 Elsevier Science Ltd. All rights reserved.
• Stereoselective Synthesis of the β-Anomer of 4‘-Thionucleosides Based on Electrophilic Glycosidation to 4-Thiofuranoid Glycals
  作者：Kazuhiro Haraguchi、Haruhiko Takahashi、Noriaki Shiina、Chikafumi Horii、Yuichi Yoshimura、Ayako Nishikawa、Eiko Sasakura、Kazuo T. Nakamura、Hiromichi Tanaka

  DOI：10.1021/jo020037x

  日期：2002.8.1

  suitable for the preparation of 3,5-O-(tetraisopropyldisiloxane-1,3-diyl) (9) and 3,5-O-(di-tert-butylsilylene) (11) 4-thioglycals. The glycosidation reactions of these 4-thioglycals were carried out, in the presence of either PhSeCl or NIS, by using silylated derivatives of uracil, thymine, cytosine, and N(6)-benzoyladenine. Among the three 4-thioglycals, 11 was found to be an excellent glycosyl donor, forming

  制备了具有不同3,5-O-甲硅烷基保护基的三种类型的4-硫呋喃基糖，并对其亲电性进行了研究。3,5-双-O-（叔丁基二甲基甲硅烷基）-4-硫呋喃类化合物糖基（5）是通过将2-脱氧-4-硫代-D-赤型戊呋喃糖（4）进行甲磺酸化并随后进行碱促进的消除反应而获得的，热消除亚砜衍生物适用于制备3,5-O-（四异丙基二硅氧烷-1,3-二基）（9）和3,5-O-（二叔丁基亚甲硅烷基）（11）4-硫代缩醛。通过使用尿嘧啶，胸腺嘧啶，胞嘧啶和N（6）-苯甲酰腺嘌呤的甲硅烷基化衍生物，在PhSeCl或NIS存在下，进行这些4-硫代糖基的糖基化反应。在这三种4-硫代糖中，有11种是出色的糖基供体，
• An Access to the β-Anomer of 4′-Thio-C-ribonucleosides: Hydroboration of 1-<i>C</i>-Aryl- or 1-<i>C</i>-Heteroaryl-4-thiofuranoid Glycals and Its Regiochemical Outcome
  作者：Kazuhiro Haraguchi、Chikafumi Horii、Yuichi Yoshimura、Fumiko Ariga、Aya Tadokoro、Hiromichi Tanaka

  DOI：10.1021/jo201100n

  日期：2011.11.4

  We have developed a novel method for the synthesis of the beta-anomer of 4'-thio-C-ribonucleosides from 3,5-O-(di-tert-butylsilylene)-4-thiofuranoid glycal. Palladium-catalyzed coupling of 1-tributylstannyl-4-thiofuranoid glycal with iodobenzene or a heteroaryl halide gave 1-C-phenyl- or 1-C-heteroaryl-glycals. Hydroboration of these glycals proceeded at the alpha-face, and subsequent alkaline hydrogen peroxide treatment of the resulting 2'-alpha-borane furnished the respective beta-anomer of 4'-thio-C-ribonucleosides. These results demonstrate that this synthetic method has a wider scope in terms of heterocyclic base structure. During this study, unexpected Markovnikov-oriented hydroboration has been observed to lead to the respective 1'-alpha-boranes. These 1'-boranes were converted into either the ring-opened structure or the 2'-deoxy derivatives depending upon their stability.