1-[2-deoxy-3,5-bis-O-(4-methylbenzoyl)-β-D-erythro-pentofuranosyl]-2,5,6-trichloroindole | 286949-68-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-[2-deoxy-3,5-bis-O-(4-methylbenzoyl)-β-D-erythro-pentofuranosyl]-2,5,6-trichloroindole
• 英文别名: 2,5,6-trichloro-1-[3,5-di-(O-p-toluoyl)-2-deoxy-β-D-ribofuranosyl]indole；[(2R,3S,5R)-3-(4-methylbenzoyl)oxy-5-(2,5,6-trichloroindol-1-yl)oxolan-2-yl]methyl 4-methylbenzoate
• CAS: 286949-68-6
• 化学式: C₂₉H₂₄Cl₃NO₅
• 分子量: 572.872
• InChiKey: BRXJDSQGIUBNJM-ZWEKWIFMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.2
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  66.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-[2-deoxy-3,5-bis-O-(4-methylbenzoyl)-β-D-erythro-pentofuranosyl]-2,5,6-trichloroindole 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以98%的产率得到1-(2-deoxy-β-D-erythro-pentofuranosyl)-2,5,6-trichloroindole
  参考文献：
  名称：

  Synthesis and Antiviral Evaluation of Trisubstituted Indole N-Nucleosides as Analogues of 2,5,6-Trichloro-1-(β-d-ribofuranosyl)benzimidazole (TCRB)

  摘要：

  2,5,6-Trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) and 2-bromo-5,6-dichloro-1-(beta-D-ribofuranosyl)benzimidazole (BDCRB) are nucleosides that exhibit strong and selective activity against human cytomegalovirus (HCMV). Selected polyhalogenated indole nucleosides have now been synthesized as 3-deaza analogues of the benzimidazole nucleosides using the sodium salt glycosylation method. 2-Benzylthio-1-[2-deoxy-3,5-bis-O-(4-methylbenzoyl)-beta-D-erythropentofuranosyl]-5,6-dichloroindole (8) was prepared stereoselectively via the coupling of a 2-deoxyribofuranosyl alpha-chloride derivative with the sodium salt of 2-benzylthio-5,6-dichloroindole (5). Compound 8 was then elaborated into the targeted 2-benzylthio-1-(beta-D-ribofuranosyl)-5,6-dichloroindole (18) in five steps. 2,5,6-Trichloro-(1-beta-D-ribofuranosyl)indole (19) was prepared using the same synthetic route with 2,5,6-trichloroindole (6) as the starting material. We were subsequently able to prepare 19 in three steps using a modification of the sodium salt glycosylation method. 2-Bromo-5,6-dichloro-1-(beta-D-ribofuranosyl)indole (25) was also prepared using the same procedures. Target compounds were tested for activity against HCMV, herpes simplex virus type 1 (HSV-1), and human herpes virus six (HHV-6) and for cytotoxicity. All of the compounds were less active against HCMV than TCRB and weakly active or inactive against HSV-1 and HHV-6.

  DOI：

  10.1021/jm990320x
• 作为产物：
  描述：

  2-（4,5-二氯-2-硝基苯基）乙酸甲酯 在 platinum(IV) oxide 咪唑 、 氢气 、 sodium hydride 、 溶剂黄146 、 三氯氧磷 作用下， 以 1,2-二氯乙烷 、 乙腈 为溶剂， 20.0 ℃ 、275.8 kPa 条件下， 反应 23.0h， 生成 1-[2-deoxy-3,5-bis-O-(4-methylbenzoyl)-β-D-erythro-pentofuranosyl]-2,5,6-trichloroindole
  参考文献：
  名称：

  Synthesis and Antiviral Evaluation of Trisubstituted Indole N-Nucleosides as Analogues of 2,5,6-Trichloro-1-(β-d-ribofuranosyl)benzimidazole (TCRB)

  摘要：

  2,5,6-Trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) and 2-bromo-5,6-dichloro-1-(beta-D-ribofuranosyl)benzimidazole (BDCRB) are nucleosides that exhibit strong and selective activity against human cytomegalovirus (HCMV). Selected polyhalogenated indole nucleosides have now been synthesized as 3-deaza analogues of the benzimidazole nucleosides using the sodium salt glycosylation method. 2-Benzylthio-1-[2-deoxy-3,5-bis-O-(4-methylbenzoyl)-beta-D-erythropentofuranosyl]-5,6-dichloroindole (8) was prepared stereoselectively via the coupling of a 2-deoxyribofuranosyl alpha-chloride derivative with the sodium salt of 2-benzylthio-5,6-dichloroindole (5). Compound 8 was then elaborated into the targeted 2-benzylthio-1-(beta-D-ribofuranosyl)-5,6-dichloroindole (18) in five steps. 2,5,6-Trichloro-(1-beta-D-ribofuranosyl)indole (19) was prepared using the same synthetic route with 2,5,6-trichloroindole (6) as the starting material. We were subsequently able to prepare 19 in three steps using a modification of the sodium salt glycosylation method. 2-Bromo-5,6-dichloro-1-(beta-D-ribofuranosyl)indole (25) was also prepared using the same procedures. Target compounds were tested for activity against HCMV, herpes simplex virus type 1 (HSV-1), and human herpes virus six (HHV-6) and for cytotoxicity. All of the compounds were less active against HCMV than TCRB and weakly active or inactive against HSV-1 and HHV-6.

  DOI：

  10.1021/jm990320x

文献信息

• Synthesis, Antiviral Activity, and Mode of Action of Some 3-Substituted 2,5,6-Trichloroindole 2‘- and 5‘-Deoxyribonucleosides
  作者：John D. Williams、Roger G. Ptak、John C. Drach、Leroy B. Townsend

  DOI：10.1021/jm0400606

  日期：2004.11.1

  time-of-addition studies using FTCRI and by the resistance of TCRB-resistant strains of HCMV to four different 3-substituted indole ribonucleosides. The 2'-deoxy analogues of the trichlorinated indole nucleosides also had potent antiviral activity, in contrast to decreased activity and selectivity observed for 2'-deoxy TCRB compared to TCRB. In addition, 3-acetyl-2,5,6-trichloro-1-(2-deoxy-beta-d-ribofuranosyl)indole

  已合成了一系列氯化吲哚核苷，并测试了其对人巨细胞病毒（HCMV）和1型单纯疱疹病毒（HSV-1）的活性以及细胞毒性。报道的3-甲酰基-2,5,6-三氯-1-（β-D-呋喃呋喃糖基）吲哚（FTCRI）和3-氰基-2,5,6-三氯的2'-和5'-脱氧衍生物通过对适当的3-未取代的糖修饰的核苷类似物进行修饰或通过将3-取代的杂环与受保护的α-氯糖进行糖基化来合成-1-（β-D-呋喃呋喃糖基）吲哚（CTCRI）。修饰的部分原因是与相应的一系列氯化苯并咪唑核糖核苷的结构相似，以及2,5,6-三氯-1-（β-D-呋喃呋喃糖基）苯并咪唑（TCRB）的5'-脱氧类似物非常重要对HCMV有效。5' FTCRI和CTCRI的-脱氧类似物的活性几乎与FTCRI和CTCRI一样，这表明氯化苯并咪唑核苷和氯化吲哚核苷的作用方式相似。使用FTCRI的加法时间研究以及HCMV的TCRB抗性菌株对四种不同的3个取代的吲哚
• Synthesis and Antiviral Evaluation of Trisubstituted Indole <i>N</i>-Nucleosides as Analogues of 2,5,6-Trichloro-1-(β-<scp>d</scp>-ribofuranosyl)benzimidazole (TCRB)
  作者：Jiong J. Chen、Yuan Wei、John C. Drach、Leroy B. Townsend

  DOI：10.1021/jm990320x

  日期：2000.6.1

  2,5,6-Trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) and 2-bromo-5,6-dichloro-1-(beta-D-ribofuranosyl)benzimidazole (BDCRB) are nucleosides that exhibit strong and selective activity against human cytomegalovirus (HCMV). Selected polyhalogenated indole nucleosides have now been synthesized as 3-deaza analogues of the benzimidazole nucleosides using the sodium salt glycosylation method. 2-Benzylthio-1-[2-deoxy-3,5-bis-O-(4-methylbenzoyl)-beta-D-erythropentofuranosyl]-5,6-dichloroindole (8) was prepared stereoselectively via the coupling of a 2-deoxyribofuranosyl alpha-chloride derivative with the sodium salt of 2-benzylthio-5,6-dichloroindole (5). Compound 8 was then elaborated into the targeted 2-benzylthio-1-(beta-D-ribofuranosyl)-5,6-dichloroindole (18) in five steps. 2,5,6-Trichloro-(1-beta-D-ribofuranosyl)indole (19) was prepared using the same synthetic route with 2,5,6-trichloroindole (6) as the starting material. We were subsequently able to prepare 19 in three steps using a modification of the sodium salt glycosylation method. 2-Bromo-5,6-dichloro-1-(beta-D-ribofuranosyl)indole (25) was also prepared using the same procedures. Target compounds were tested for activity against HCMV, herpes simplex virus type 1 (HSV-1), and human herpes virus six (HHV-6) and for cytotoxicity. All of the compounds were less active against HCMV than TCRB and weakly active or inactive against HSV-1 and HHV-6.