6-chloro-9-(2-deoxy-3,5-bis-O-(tert-butyldimethylsilyl)-β-D-erythro-pentofuranosyl)purine | 106568-82-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 6-chloro-9-(2-deoxy-3,5-bis-O-(tert-butyldimethylsilyl)-β-D-erythro-pentofuranosyl)purine
• 英文别名: 9-[3',5'-bis-O-(tert-butyldimethylsilyl)-2-deoxy-β-D-erythro-pentofuranosyl]-6-chloropurine；tert-butyl-[[(2R,3S,5R)-3-[tert-butyl(dimethyl)silyl]oxy-5-(6-chloropurin-9-yl)oxolan-2-yl]methoxy]-dimethylsilane
• CAS: 106568-82-5
• 化学式: C₂₂H₃₉ClN₄O₃Si₂
• 分子量: 499.201
• InChiKey: JQPYWNZWOKYRMJ-GVDBMIGSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.18
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  71.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-chloro-9-(2-deoxy-3,5-bis-O-(tert-butyldimethylsilyl)-β-D-erythro-pentofuranosyl)purine 在 triethylamine trihydrofluoride 、 甲基三苯氧基碘磷 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.75h， 生成 (2R,3S,5R)-5-(7,8-dihydroimidazo[2,1-f]purin-3-yl)-2-(hydroxymethyl)oxolan-3-ol
  参考文献：
  名称：

  Synthesis of 1,N⁶-Ethano-2‘-deoxyadenosine, a Metabolic Product of 1,3-Bis(2-chloroethyl)nitrosourea, and Its Incorporation into Oligomeric DNA

  摘要：

  1,N-6-Ethano-2'-deoxyadenosine (1) is one of the adducts formed during DNA reaction with the antitumor agent, 1,3-bis(2-chloroethyl)nitrosourea (BCNU), and was synthesized and incorporated into a site-specific deoxyoligonucleotide for the first time. The product 6-chloropurine-2'-deoxyriboside (11) was prepared in high yield by the reaction of 2'-deoxyinosine (6) with SOCl2, which then was derivatized to give compound 12 using tert-butyldimethylsilyl chloride, which was then reacted with 2-hydroxyethylamine to produce compound 13 in 86% yield. Reaction of 13 with (PhO)(8)P+MeI- in DMF gave the cyclized 1,N-6-ethano derivative 10 in 67% yield. Desilylation of 10 with triethylamine trihydrofluoride in THF gave 1,N-6-ethano-dA (1) in 91% yield. Tritylation of compound 1 with DMT+BF4- gave the 5'-O-DMT product 14 in 62% yield, which then was phosphitylated with 2-cyanoethyl N,N-diisopropylchlorophosphoramidite, which yielded a 1:1 mixture of the diastereoisomers 15 in 71% yield. This fully protected compound 15 was incorporated site-specifically into a 25-mer oligonucleotide. The coupling efficiency of ethano-dA phosphoramidite was 93%. Enzymatic hydrolysis and analysis by HPLC confirmed the incorporation of ethano-dA and base composition of the DNA oligomer. The latter is now under investigation for its biochemical and physical properties.

  DOI：

  10.1021/jo980170i
• 作为产物：
  描述：

  2'-脱氧肌苷 在 咪唑 、 氯化亚砜 、 碳酸氢钠 、 三氟乙酸酐 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 6-chloro-9-(2-deoxy-3,5-bis-O-(tert-butyldimethylsilyl)-β-D-erythro-pentofuranosyl)purine
  参考文献：
  名称：

  Synthesis of 1,N⁶-Ethano-2‘-deoxyadenosine, a Metabolic Product of 1,3-Bis(2-chloroethyl)nitrosourea, and Its Incorporation into Oligomeric DNA

  摘要：

  1,N-6-Ethano-2'-deoxyadenosine (1) is one of the adducts formed during DNA reaction with the antitumor agent, 1,3-bis(2-chloroethyl)nitrosourea (BCNU), and was synthesized and incorporated into a site-specific deoxyoligonucleotide for the first time. The product 6-chloropurine-2'-deoxyriboside (11) was prepared in high yield by the reaction of 2'-deoxyinosine (6) with SOCl2, which then was derivatized to give compound 12 using tert-butyldimethylsilyl chloride, which was then reacted with 2-hydroxyethylamine to produce compound 13 in 86% yield. Reaction of 13 with (PhO)(8)P+MeI- in DMF gave the cyclized 1,N-6-ethano derivative 10 in 67% yield. Desilylation of 10 with triethylamine trihydrofluoride in THF gave 1,N-6-ethano-dA (1) in 91% yield. Tritylation of compound 1 with DMT+BF4- gave the 5'-O-DMT product 14 in 62% yield, which then was phosphitylated with 2-cyanoethyl N,N-diisopropylchlorophosphoramidite, which yielded a 1:1 mixture of the diastereoisomers 15 in 71% yield. This fully protected compound 15 was incorporated site-specifically into a 25-mer oligonucleotide. The coupling efficiency of ethano-dA phosphoramidite was 93%. Enzymatic hydrolysis and analysis by HPLC confirmed the incorporation of ethano-dA and base composition of the DNA oligomer. The latter is now under investigation for its biochemical and physical properties.

  DOI：

  10.1021/jo980170i

文献信息

• SENSITIVE OLIGONUCLEOTIDE SYNTHESIS USING SULFUR-BASED FUNCTIONS AS PROTECTING GROUPS AND LINKERS
  申请人：Fang Shiyue

  公开号：US20210032281A1

  公开（公告）日：2021-02-04

  Embodiments for the synthesis of sensitive oligonucleotides as well as insensitive oligonucleotides are provided. Sulfur-based groups are used for the protection of exo-amino groups of nucleobases, phosphate groups and 2′-OH groups, and as cleavable linker for linking oligonucleotides to a support. Oligonucleotide syntheses are achieved under typical conditions using phosphoramidite chemistry with important modifications. To prevent replacing sulfur-based protecting groups by acyl groups via cap-exchange, special capping agents are used. To retain hydrophobic tag to assist RP HPLC purification, special phosphoramidites are used in the last synthetic cycle. With the sulfur-based groups for protection and linking, oligonucleotide deprotection and cleavage are achieved via oxidation followed by beta-elimination under mild conditions. Therefore, besides for insensitive oligonucleotide synthesis, the embodiments of the invention are capable for the synthesis of oligonucleotide analogs containing sensitive functional groups that cannot survive the harsh conditions used in prior art oligonucleotide synthesis technologies.

  本发明提供了用于合成敏感寡核苷酸和不敏感寡核苷酸的实施方案。使用基于硫的基团来保护核苷酸碱基的exo-氨基团、磷酸基团和2′-OH基团，并且作为可裂解的连接剂将寡核苷酸连接到支持物上。寡核苷酸的合成是在典型条件下使用磷酰亚胺化学进行的，并进行了重要的修改。为了防止通过帽交换将基于硫的保护基团替换为酰基，使用了特殊的封端剂。为了保留亲脂性标签以协助反相高效液相色谱（RP HPLC）纯化，在最后的合成周期中使用了特殊的磷酰亚胺。使用基于硫的基团进行保护和连接，寡核苷酸的脱保护和裂解是通过氧化随后在温和条件下进行beta-消除实现的。因此，除了用于不敏感寡核苷酸的合成外，本发明的实施方案还能够合成包含在先前的寡核苷酸合成技术中使用的严酷条件下无法存活的敏感功能团的寡核苷酸类似物。
• A Systematic Study of the Synthesis of 2ʹ-Deoxynucleosides by Mitsunobu Reaction
  作者：Kohji Seio、Munefumi Tokugawa、Kazuhei Kaneko、Takashi Shiozawa、Yoshiaki Masaki

  DOI：10.1055/s-0036-1588445

  日期：2017.9

  preparation of synthetic 2′-deoxynucleosides, which have various biological and biotechnological applications. In this work, the Mitsunobu-based synthesis of 2′-deoxynucleosides was systematically studied. The effect of phosphine, azodicarbonyl reagent, and solvent on the product yield and α/β ratio was investigated, and the highest yield and β-selectivity were obtained using ( n -Bu) 3 P and 1,1′-(azodic

  Mitsunobu 反应已成为制备具有各种生物学和生物技术应用的合成 2'-脱氧核苷的重要替代方法。在这项工作中，系统研究了基于光信的 2'-脱氧核苷合成。考察了膦、偶氮二羰基试剂和溶剂对产物收率和α/β比的影响，使用( n -Bu) 3 P和1,1'-(偶氮二羰基)二哌啶获得了最高的收率和β-选择性在 DMF 中。该反应成功地应用于各种核碱基类似物。
• Synthesis of Adducts of <i>o</i>-Quinone Metabolites of Carcinogenic Polycyclic Aromatic Hydrocarbons with 2‘-Deoxyribonucleosides
  作者：Qing Dai、Chongzhao Ran、Ronald G. Harvey

  DOI：10.1021/ol0475358

  日期：2005.3.1

  text] The first syntheses of the adducts formed in the reactions of o-quinone metabolites of carcinogenic polycyclic aromatic hydrocarbons (BPQ and BAQ) at 2'-deoxyadenosine and 2'-deoxyguanosine sites in DNA are reported. These syntheses entail Pd-catalyzed coupling of protected amine derivatives of catechols with suitably protected halopurine analogues of 2'-deoxyribonucleosides.

  [结构：见正文]报告了在致癌多环芳烃（BPQ和BAQ）的邻醌代谢产物在DNA中2'-脱氧腺苷和2'-脱氧鸟苷位点反应中形成的加合物的首次合成。这些合成需要邻苯二酚的受保护胺衍生物与2'-脱氧核糖核苷的适当保护的卤代嘌呤类似物的Pd催化偶联。
• Palladium-Catalyzed Synthesis of Nucleoside Adducts from Bay- and Fjord-Region Diol Epoxides
  作者：Elise Champeil、Padmanava Pradhan、Mahesh K. Lakshman

  DOI：10.1021/jo070204z

  日期：2007.7.1

  tribenzoate as compared to the bay-region BaP amino tribenzoate. In contrast to reactions leading to the dA adducts, the C−N reactions of both BaP and BcPh amino tribenzoates with the 2-bromo-2‘-deoxyinosine derivative proceeded in comparable yields. This seems to indicate that such Pd-catalyzed adduct forming reactions at the C-6 position may be influenced by steric constraints of the amine component

  钯催化的CN键的形成已用于合成苯并[ a ] py（B a P）系列1（syn）和苯并[ c ]的2'-脱氧腺苷（dA）和2'-脱氧鸟苷（dG）加合物。菲（B c Ph）系列2（反）二醇环氧化物。对于这一点，（±）-10α氨基7β，8α，9β-trisbenzoyloxy -7,8,9,10-四氢B一个P和（±）-1β氨基2α，3α，4β-trisbenzoyloxy-1， 2,3,4-四氢B c Ph与6-卤代9- [3,5-双-O-（叔丁基二甲基甲硅烷基）-β- d-赤型-戊呋喃糖基]嘌呤和O 6-苄基-3偶联'，5'-bis- O-（叔-丁基二甲基甲硅烷基）-2-溴-2'-脱氧肌苷，使用（±）-BINAP-Pd络合物和Cs 2 CO 3。对于dA加合物的合成，分析了6氯代和6溴嘌呤核苷衍生物与烃基氨基三苯甲酸酯的CN偶联反应。对于B a P氨基三苯甲酸酯，6-氯核苷可提供令人满意的结果，而6-溴类似物被证明对B
• The Selective Synthesis of Metallanucleosides and Metallanucleotides: A New Tool for the Functionalization of Nucleic Acids
  作者：Mamen Martín-Ortíz、Mar Gómez-Gallego、Carmen Ramírez de Arellano、Miguel A. Sierra

  DOI：10.1002/chem.201202327

  日期：2012.10.1

  Nucleobases team up: The efficient and selective preparation of purine‐derived metallanucleosides, metallanucleotides, and metalladinucleotides having MC bonds (M=IrIII, RhIII) is reported for the first time (see scheme). The results presented may be applied to the synthesis of functionalized nucleic acids, or DNA/RNA‐modified segments.

  核碱基组队：嘌呤衍生metallanucleosides，metallanucleotides和metalladinucleotides具有M的有效和选择性制备 C键（M = IR III，铑III）报道首次（参见方案）。给出的结果可用于功能化核酸或DNA / RNA修饰片段的合成。