1-(5-O-tert-butyldimethylsilyl-2-deoxy-β-D-erythro-pentofuranosyl)imidazo[4,5-d]pyridazin-4(5H)-one | 260562-59-2

• 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: 1-(5-O-tert-butyldimethylsilyl-2-deoxy-β-D-erythro-pentofuranosyl)imidazo[4,5-d]pyridazin-4(5H)-one
• 英文别名: 5'-O-Tert-butyldimethylsilyl-2'-deoxyinosine；9-[(2R,4S,5R)-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-4-hydroxyoxolan-2-yl]-1H-purin-6-one
• CAS: 260562-59-2
• 化学式: C₁₆H₂₆N₄O₄Si
• 分子量: 366.492
• InChiKey: GHCYFLRPIRMTTP-QJPTWQEYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.79
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  98
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(5-O-tert-butyldimethylsilyl-2-deoxy-β-D-erythro-pentofuranosyl)imidazo[4,5-d]pyridazin-4(5H)-one 在 4-二甲氨基吡啶 、 偶氮二异丁腈 、 四丁基氟化铵 、 三正丁基氢锡 、 三乙胺 作用下， 以 四氢呋喃 、 甲苯 、 乙腈 为溶剂， 反应 11.0h， 生成 2',3'-二脱氧肌苷
  参考文献：
  名称：

  2'，3'-二脱氧咪唑-和nu-三唑并[4,5-d]哒嗪核苷的合成及抗HIV评价。

  摘要：

  合成了2,8-diaza-3-deazainosine的2'-deoxy和2'，3'-deideoxynucleosides和2-aza-3-deazainosine的2'，3'-deideoxynucleosides的合成途径描述了这些新颖的核苷。2-aza-3-deazainosine的2'，3'-二脱氧核苷（1）的制备涉及2'-deoxy-3'-咪唑啉中间体与n-Bu3SnH和AlBN的脱氧作用。后者的核苷由2-氮杂-3-脱氮芥子苷的已知的2'-脱氧衍生物合成。由2'-脱氧类似物进行1的三步合成，收率为40％。与其以相同的方式，即2'-脱氧核苷的脱氧，而不是合成2,8-二氮杂-3-脱氮肌苷的相应的2'，3'-二脱氧核苷（2），而是选择了一种更具成本效益的途径。该途径涉及5'-保护的2'，3'-硫代碳酸酯衍生物的还原裂解，以提供2'-和3'-脱氧异构体的混合物。该混合物没有分离，但是通

  DOI：

  10.1016/s0968-0896(99)00184-4
• 作为产物：
  描述：

  2'-脱氧肌苷 、 叔丁基二甲基氯硅烷 在 吡啶 作用下， 生成 1-(5-O-tert-butyldimethylsilyl-2-deoxy-β-D-erythro-pentofuranosyl)imidazo[4,5-d]pyridazin-4(5H)-one
  参考文献：
  名称：

  Phosphonomethyl Oligonucleotides as Backbone-Modified Artificial Genetic Polymers

  摘要：

  Although several synthetic or xenobiotic nucleic acids (XNAs) have been shown to be viable genetic materials in vitro, major hurdles remain for their in vivo applications, particularly orthogonality. The availability of XNAs that do not interact with natural nucleic acids and are not affected by natural DNA processing enzymes, as well as specialized XNA processing enzymes that do not interact with natural nucleic acids, is essential. Here, we report 3'-2' phosphonomethylthreosyl nucleic acid (tPhoNA) as a novel XNA genetic material and a prime candidate for in vivo XNA applications. We established routes for the chemical synthesis of phosphonate nucleic acids and phosphorylated monomeric building blocks, and we demonstrated that DNA duplexes were destabilized upon replacement with tPhoNA. We engineered a novel tPhoNA synthetase enzyme and, with a previously reported XNA reverse transcriptase, demonstrated that tPhoNA is a viable genetic material (with an aggregate error rate of approximately 17 X 10(-3) per base) compatible with the isolation of functional XNAs. In vivo experiments to test tPhoNA orthogonality showed that the E. coli cellular machinery had only very limited potential to access genetic information in tPhoNA. Our work is the first report of a synthetic genetic material modified in both sugar and phosphate backbone moieties and represents a significant advance in biorthogonality toward the introduction of XNA systems in vivo.

  DOI：

  10.1021/jacs.8b03447

文献信息

• [EN] ANTI-VIRAL AND ANTI-TUMORAL COMPOUNDS<br/>[FR] COMPOSÉS ANTI-VIRAUX ET ANTI-TUMORAUX
  申请人：YEDA RES & DEV

  公开号：WO2022038539A3

  公开（公告）日：2022-03-31
• Synthesis and anti-HIV evaluation of 2′,3′-dideoxy imidazo- and ν-triazolo[4,5-d]pyridazine nucleosides
  作者：Jacqueline C. Bussolari、Raymond P. Panzica

  DOI：10.1016/s0968-0896(99)00184-4

  日期：1999.11

  latter nucleoside was synthesized from the known 2'-deoxy derivative of 2-aza-3-deazainosine. The three-step synthesis of 1 from the 2'-deoxy analogue was accomplished in 40% overall yield. Rather than synthesize the corresponding 2',3'-dideoxynucleoside (2) of 2,8-diaza-3-deazainosine in the same manner, i.e. deoxygenation of the 2'-deoxynucleoside, a more cost-effective route was chosen. This pathway involved

  合成了2,8-diaza-3-deazainosine的2'-deoxy和2'，3'-deideoxynucleosides和2-aza-3-deazainosine的2'，3'-deideoxynucleosides的合成途径描述了这些新颖的核苷。2-aza-3-deazainosine的2'，3'-二脱氧核苷（1）的制备涉及2'-deoxy-3'-咪唑啉中间体与n-Bu3SnH和AlBN的脱氧作用。后者的核苷由2-氮杂-3-脱氮芥子苷的已知的2'-脱氧衍生物合成。由2'-脱氧类似物进行1的三步合成，收率为40％。与其以相同的方式，即2'-脱氧核苷的脱氧，而不是合成2,8-二氮杂-3-脱氮肌苷的相应的2'，3'-二脱氧核苷（2），而是选择了一种更具成本效益的途径。该途径涉及5'-保护的2'，3'-硫代碳酸酯衍生物的还原裂解，以提供2'-和3'-脱氧异构体的混合物。该混合物没有分离，但是通
• Phosphonomethyl Oligonucleotides as Backbone-Modified Artificial Genetic Polymers
  作者：Chao Liu、Christopher Cozens、Faten Jaziri、Jef Rozenski、Amandine Maréchal、Shrinivas Dumbre、Valérie Pezo、Philippe Marlière、Vitor B. Pinheiro、Elisabetta Groaz、Piet Herdewijn

  DOI：10.1021/jacs.8b03447

  日期：2018.5.30

  Although several synthetic or xenobiotic nucleic acids (XNAs) have been shown to be viable genetic materials in vitro, major hurdles remain for their in vivo applications, particularly orthogonality. The availability of XNAs that do not interact with natural nucleic acids and are not affected by natural DNA processing enzymes, as well as specialized XNA processing enzymes that do not interact with natural nucleic acids, is essential. Here, we report 3'-2' phosphonomethylthreosyl nucleic acid (tPhoNA) as a novel XNA genetic material and a prime candidate for in vivo XNA applications. We established routes for the chemical synthesis of phosphonate nucleic acids and phosphorylated monomeric building blocks, and we demonstrated that DNA duplexes were destabilized upon replacement with tPhoNA. We engineered a novel tPhoNA synthetase enzyme and, with a previously reported XNA reverse transcriptase, demonstrated that tPhoNA is a viable genetic material (with an aggregate error rate of approximately 17 X 10(-3) per base) compatible with the isolation of functional XNAs. In vivo experiments to test tPhoNA orthogonality showed that the E. coli cellular machinery had only very limited potential to access genetic information in tPhoNA. Our work is the first report of a synthetic genetic material modified in both sugar and phosphate backbone moieties and represents a significant advance in biorthogonality toward the introduction of XNA systems in vivo.