5′-O-(4,4′-Dimethoxytrityl)-N²-isobutyryl-2′-deoxyguanosine-3′-O-(2-thio-1,3,2-oxathiaphospholane)

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 5′-O-(4,4′-Dimethoxytrityl)-N²-isobutyryl-2′-deoxyguanosine-3′-O-(2-thio-1,3,2-oxathiaphospholane)
• 英文别名: N-[9-[(2R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-[(2-sulfanylidene-1,3,2lambda5-oxathiaphospholan-2-yl)oxy]oxolan-2-yl]-6-oxo-1H-purin-2-yl]-2-methylpropanamide；N-[9-[(2R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-[(2-sulfanylidene-1,3,2λ5-oxathiaphospholan-2-yl)oxy]oxolan-2-yl]-6-oxo-1H-purin-2-yl]-2-methylpropanamide
• 化学式: C₃₇H₄₀N₅O₈PS₂
• 分子量: 777.859
• InChiKey: KPOCCKKHKYZBNX-FLZZYNHXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  53
• 可旋转键数：
  13
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  201
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  5′-O-(4,4′-Dimethoxytrityl)-N²-isobutyryl-2′-deoxyguanosine-3′-O-(2-thio-1,3,2-oxathiaphospholane) 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 3-羟基丙腈 、 溶剂黄146 、 ammonium hydroxide 作用下， 以 乙腈 为溶剂， 反应 12.25h， 以40%的产率得到Thiophosphoric acid O-[(2R,3S,5R)-5-(2-amino-6-oxo-1,6-dihydro-purin-9-yl)-2-hydroxymethyl-tetrahydro-furan-3-yl] ester; compound with ammonia
  参考文献：
  名称：

  Thiophosphorylation of Biologically Relevant Alcohols by the Oxathiaphospholane Approach

  摘要：

  2-烷氧基-2-硫代-1,3,2-氧硫磷烷可以方便地通过一步法转化为相应醇的磷酸硫代单酯，该方法涉及在DBU存在下与3-羟基丙腈反应，随后用氨水处理。通过这种方法制备了一系列核苷-3′-O-和5′-O-磷酸硫代酯，以及选定多元醇的磷酸硫代衍生物。

  DOI：

  10.1055/s-2002-31913
• 作为产物：
  描述：

  在 sulfur 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 生成 5′-O-(4,4′-Dimethoxytrityl)-N²-isobutyryl-2′-deoxyguanosine-3′-O-(2-thio-1,3,2-oxathiaphospholane)
  参考文献：
  名称：

  Diastereomers of Nucleoside 3'-O-(2-Thio-1,3,2-oxathia(selena)phospholanes): Building Blocks for Stereocontrolled Synthesis of Oligo(nucleoside phosphorothioate)s

  摘要：

  Diastereomerically pure 5'-O-DMT-nucleoside 3'-O-(2-thio-1,3,2-oxathiaphospholanes) (3) and their oxathiaphospholane ring-substituted analogues (20) were used for the synthesis of stereoregular oligo(nucleoside phosphorothioate)s (S-Oligos). The oxathiaphospholane ring-opening condensation requires the presence of strong organic base, preferably DBU. The yield of a single coupling step is ca. 95% and resulting S-Oligos are free of nucleobase- and sugar-phosphorothioate backbone modifications. The diastereomeric purity of products was estimated on the basis of diastereoselective degradation with Nuclease P1 and a mixture of snake venom phosphodiesterase and Serratia marcescens endonuclease. Thermal dissociation studies of heteroduplexes S-Oligos/DNA and S-Oligos/RNA showed that their stability is stereochemistry- and sequence-dependent.

  DOI：

  10.1021/ja00154a001

文献信息

• Synthesis of PS/PO-chimeric oligonucleotides using mixed oxathiaphospholane and phosphoramidite chemistry
  作者：Ewa Radzikowska、Janina Baraniak

  DOI：10.1039/c4ob01837k

  日期：——

  Chimeric oligonucleotides containing phosphodiester and phosphorothioate linkages have been obtained using the solid phase synthesis. The oligonucleotide parts possessing natural internucleotide phosphate bonds were assembled using commercially available nucleoside 3′-O-(2-cyanoethyl-N,N-diisopropylamino)phosphoramidites 7 whereas the phosphorothioate segment was built using nucleoside 3′-O-(2-thio-1

  使用固相合成已经获得了包含磷酸二酯和硫代磷酸酯键的嵌合寡核苷酸。使用可商购的核苷3' - O-（2-氰基乙基-N，N-二异丙基氨基）亚磷酰胺7组装具有天然核苷酸间磷酸键的寡核苷酸部分，而硫代磷酸酯片段则使用核苷3' - O-（2-硫代- 1,3,2-氧代磷酰胺）3。氧化步骤对于将亚磷酸酯键转化为磷酸根部分至关重要，该氧化步骤是使用叔胺进行的-丁基过氧三甲基硅烷，该试剂对二酯硫代磷酸酯键无害。当使用P-非对映体纯核苷3'- O-（2-硫代-1,3,2-氧代磷杂环戊烷）单体时，所得的嵌合主链保留了硫代磷酸酯单元的P-立体有规性。
• Thiophosphorylation of Biologically Relevant Alcohols by the Oxathiaphospholane Approach
  作者：Magdalena Olesiak、Danuta Krajewska、Ewa Wasilewska、Dariusz Korczyński、Janina Baraniak、Andrzej Okruszek、Wojciech J. Stec

  DOI：10.1055/s-2002-31913

  日期：——

  2-Alkoxy-2-thiono-1,3,2-oxathiaphospholanes are readily transformed into phosphorothioate monoesters of the corresponding alcohols in a one-pot process, involving the reaction with 3-hydroxypropionitrile in the presence of DBU, followed by treatment with aqueous ammonia. In this way a series of nucleoside-3′-O- and 5′-O-phosphorothioates were prepared, as well as phosphorothioate derivatives of selected polyols.

  2-烷氧基-2-硫代-1,3,2-氧硫磷烷可以方便地通过一步法转化为相应醇的磷酸硫代单酯，该方法涉及在DBU存在下与3-羟基丙腈反应，随后用氨水处理。通过这种方法制备了一系列核苷-3′-O-和5′-O-磷酸硫代酯，以及选定多元醇的磷酸硫代衍生物。
• Diastereomers of Nucleoside 3'-O-(2-Thio-1,3,2-oxathia(selena)phospholanes): Building Blocks for Stereocontrolled Synthesis of Oligo(nucleoside phosphorothioate)s
  作者：Wojciech J. Stec、Andrzej Grajkowski、Anna Kobylanska、Boleslaw Karwowski、Maria Koziolkiewicz、Konrad Misiura、Andrzej Okruszek、Andrzej Wilk、Piotr Guga、Malgorzata Boczkowska

  DOI：10.1021/ja00154a001

  日期：1995.12

  Diastereomerically pure 5'-O-DMT-nucleoside 3'-O-(2-thio-1,3,2-oxathiaphospholanes) (3) and their oxathiaphospholane ring-substituted analogues (20) were used for the synthesis of stereoregular oligo(nucleoside phosphorothioate)s (S-Oligos). The oxathiaphospholane ring-opening condensation requires the presence of strong organic base, preferably DBU. The yield of a single coupling step is ca. 95% and resulting S-Oligos are free of nucleobase- and sugar-phosphorothioate backbone modifications. The diastereomeric purity of products was estimated on the basis of diastereoselective degradation with Nuclease P1 and a mixture of snake venom phosphodiesterase and Serratia marcescens endonuclease. Thermal dissociation studies of heteroduplexes S-Oligos/DNA and S-Oligos/RNA showed that their stability is stereochemistry- and sequence-dependent.