2,3,5-tri-O-benzoyl-β-D-ribosyl isocyanate | 21823-89-2

• 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: 2,3,5-tri-O-benzoyl-β-D-ribosyl isocyanate
• 英文别名: tri-O-benzoyl-β-D-ribofuranosyl isocyanate；[(2R,3R,4R,5R)-3,4-dibenzoyloxy-5-isocyanatooxolan-2-yl]methyl benzoate
• CAS: 21823-89-2
• 化学式: C₂₇H₂₁NO₈
• 分子量: 487.466
• InChiKey: WCRZYMGBBGTPGP-MOUTVQLLSA-N

物化性质

• 沸点：
  622.3±55.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  36
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  118
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2,3,5-tri-O-benzoyl-β-D-ribosyl isocyanate 在 sodium methylate 作用下， 以 丙酮 、 甲苯 为溶剂， 反应 4.0h， 生成 (3AS,5R,6R,6AR)-6-羟基-5-(羟甲基)四氢呋喃并[2,3-D]噁唑-2(5H)-酮
  参考文献：
  名称：

  Synthesis of N4-Amino and N4-Hydroxy Derivatives of 5-Azacytidine. A Facile Rearrangement of the N4-Amino Derivative to 5-(3-β-D-Ribofuranosylureido)-1H-1,2,4-triazole

  摘要：

  甲氧基核糖三嗪醇（4）在甲醇中与肼反应生成粗品4-肼基-1-β-D-核糖呋喃糖苷-1,3,5-三嗪-2（1H）-酮（N4-氨基-5-氮杂胞苷）（2），迅速重排为异构体5-核糖尿素三唑（6）。重排在2的水溶液中也很容易进行。碱水解6得到混合物5-尿素三唑（7）和5-氨基三唑（8）。酸水解6只得到7。这种化合物也可通过5-氨基-1-氨基甲酰基三唑（9）的热重排或氰（甲酰）胍氯化水合物与肼反应制备。甲酰化的甲氧基核糖三嗪醇（4a）在甲醇中与肼反应只得到重排产物6a。三苯甲酰核糖异氰酸酯（12）与氨基三唑（8）反应得到1-三唑羧酰胺基三苯甲酰核糖（13），经甲醇解得到噁唑核糖呋喃糖（14）和氨基三唑（8）。化合物14也可通过阻断的核糖氨酸酯（16）的甲醇解获得。甲氧基核糖三嗪醇（4）在甲醇中与羟胺反应生成4-羟胺基-1-β-D-核糖呋喃糖苷-1,3,5-三嗪-2（1H）-酮（N4-羟基-5-氮杂胞苷）（3），在过量羟胺作用下生成1-氰基-1-羟基-5-β-D-核糖呋喃异尿素（19）。甲氧-1,3,5-三嗪醇（18）与甲醇中的羟胺溶液反应生成4-羟胺基-1-甲基-1,3,5-三嗪-2（1H）-酮（N4-羟基-1-甲基-5-氮杂胞嘧啶）（17）。氰（甲酰）胍氯化水合物（10）与羟胺盐酸盐加热反应生成三尿素（21）。讨论了甲氧基核糖三嗪醇（4）与肼和羟胺的反应机制。化合物2、6和19未表现出明显的抗菌或细胞毒活性。

  DOI：

  10.1135/cccc20040905
• 作为产物：
  描述：

  1-乙酰氧基-2,3,5-三苯甲酰氧基-1-beta-D-呋喃核糖 在 盐酸 作用下， 以 乙醚 、 甲苯 为溶剂， 反应 75.0h， 生成 2,3,5-tri-O-benzoyl-β-D-ribosyl isocyanate
  参考文献：
  名称：

  Syntheses and structure assignments of six azolinone ribonucleosides

  摘要：

  DOI：

  10.1021/jo00342a020

文献信息

• Synthesis of Some 6-Substituted 5-Azacytidines
  作者：Naeem B. Hanna、Milena Masojídková、Pavel Fiedler、Alois Pískala

  DOI：10.1135/cccc19980222

  日期：——

  Protected 6-substituted benzyl, phenyl and chloromethyl derivatives of 5-azacytidine 8-10 have been prepared by addition of phenylacetyl- (2), benzoyl- (3) or (chloroacetyl)guanidine (4) to 2,3,5-tri-O-benzoyl-β-D-ribosyl isocyanate (1) and subsequent silylation-mediated cyclization of the obtained acyl(carbamoyl)guanidines 5-7. 4-Amino-6-phenyl-1,3,5-triazin-2(1H)-one (12) was obtained by condensation of carbamoylguanidine (13) with methyl benzoate in presence of methanolic sodium methoxide or by condensation of 13 with triethyl orthobenzoate in N,N-dimethylformamide. Stannic chloride catalyzed condensation of silylated 6-phenyl derivative 11 with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribose (14) in 1,2-dichloroethane afforded a 1.2 : 1 mixture of N¹ and N³ nucleosides 9 and 15, respectively. Methanolysis of the protected compounds 8-10 and 15 gave the respective free nucleosides 16-19. The latter compounds inhibited the growth of bacteria E. coli B to a much lower extent than the unsubstituted 5-azacytidine.

  已保护的6-取代苄基、苯基和氯甲基衍生物5-氮杂胞苷8-10已通过将苯乙酰- (2)、苯甲酰- (3)或(氯乙酰)胍基 (4)加入2,3,5-三-O-苯甲酰-β-D-核糖基异氰酸酯 (1)并随后通过得到的酰(氨基甲酰)胍基物 5-7 进行硅烷化介导的环化反应制备。通过在甲醇钠甲醇醇溶液中将氨基甲酰胍基 (13) 与甲苯酸甲酯缩合或将 13 与三乙基邻苯甲酸酯在 N,N-二甲基甲酰胺中缩合得到了4-氨基-6-苯基-1,3,5-三嗪-2(1H)-酮 (12)。在1,2-二氯乙烷中，硅烷化的6-苯基衍生物 11 与1-O-乙酰-2,3,5-三-O-苯甲酰-β-D-核糖 (14) 经锡氯化物催化缩合得到了N¹和N³核苷 9 和 15 的1.2:1混合物。对保护化合物 8-10 和 15 进行甲醇解后得到相应的自由核苷 16-19。后者抑制了细菌 E. coli B 的生长，但比未取代的5-氮杂胞苷的作用要弱得多。
• Synthesis and Biological Activity of N4-Methyl-5-azacytidines
  作者：Naeem B. Hanna、Milena Masojídková、Alois Pískala

  DOI：10.1135/cccc19980713

  日期：——

  Protected N⁴-methyl and N⁴,N⁴-dimethyl derivatives of 5-azacytidine 3 and 4 were prepared by selective aminolysis of benzoylated 4-methoxy-1-(β-D-ribofuranosyl)-1,3,5-triazin-2(1H)-one 5, by glycosylation of silylated N⁴-methyl- or N⁴,N⁴-dimethyl-5-azacytosines 7 and 8 with 2,3,5-tri-O-benzoyl-α,β-D-ribofuranosyl chloride (11) or by several modifications of the isocyanate method. By the isocyanate approach, also the α-D anomer of protected N⁴-methyl-5-azacytidine 17 was obtained as a minor product. The protected dimethyl derivative 4 was also obtained by the reaction of isobiuret 22 with dimethylformamide dimethyl acetal. The free nucleosides 1 and 2 were obtained either by aminolysis of the free methoxy nucleoside 23 with methylamine or dimethylamine, respectively, or by methanolysis or ammonolysis of the corresponding benzoyl derivatives 3 and 4. The free α-D anomer 24 was obtained by methanolysis of its tribenzoate 17. Nucleosides 1 and 2 exhibited a lower antibacterial, antitumor and antiviral activity than the unsubstituted 5-azacytidine.

  通过对苯酰化的4-甲氧基-1-(β-D-核糖苷)-1,3,5-三嗪-2(1H)-酮5进行选择性氨解反应，制备了5-氮杂胞嘧啶的保护N4-甲基和N4,N4-二甲基衍生物3和4，通过对硅烷化的N4-甲基或N4,N4-二甲基-5-氮杂胞嘧啶7和8与2,3,5-三-O-苯酰-α,β-D-核糖苷氯化物(11)的糖基化反应，或通过异氰酸酯法的几种修饰方法制备。通过异氰酸酯法，还得到了保护的N4-甲基-5-氮杂胞嘧啶的α-D异构体17作为副产物。保护的二甲基衍生物4也可通过异丁脲22与二甲基甲酰胺二甲基缩醛反应得到。游离核苷1和2可通过游离的甲氧基核苷23分别与甲胺或二甲胺氨解，或通过相应的苯酰衍生物3和4的甲醇解或氨解得到。游离的α-D异构体24可通过其三苯甲酸酯17的甲醇解得到。核苷1和2的抗菌、抗肿瘤和抗病毒活性均低于未取代的5-氮杂胞嘧啶。
• Piskala, Alois; Hanna, Naeem B.; Zajicek, Jaroslav, Collection of Czechoslovak Chemical Communications, 1989, vol. 54, # 9, p. 2502 - 2511
  作者：Piskala, Alois、Hanna, Naeem B.、Zajicek, Jaroslav、Cihak, Alois

  DOI：——

  日期：——
• 6-Methyl-5-Azacytidine-Synthesis, Conformational Properties and Biological Activity. A Comparison of Molecular Conformation with 5-Azacytidine
  作者：Naeem B. Hanna +、Jaroslav Zajíček ++、Alois Pískala

  DOI：10.1080/07328319708002528

  日期：1997.1

  The title compound was prepared by the isocyanate procedure and the trimethylsilyl method. The measurement of H-1 NMR spectrum of 6-methyl-5-azacytidine (1) revealed a preference of gamma(t) (46%) rotamer around C(5')-C(4') bond, a predominance of N conformation of the ribose ring (K-eq 0.33) and a preference of syn conformation around the C-N glycosyl bond. An analogous measurement of 5-azacytidine has shown a preference of gamma(+) (60%) rotamer around the C(5')-C(4') bond, a predominance of N conformation of the ribose ring (K-eq 0.41) and a preference of anti conformation around the C-N glycosyl bond. 6-Methyl-5-azacytidine (1) inhibits the growth of bacteria E. coli to the extent of 85% at 4000 mu M concentration and the growth of LoVo/L, a human colon carcinoma cell line, to the extent of 30% at 100 mu M concentration but did not inhibit L1210 cells at less than or equal to 100 mu M concentration. 6-Methyl-5-azacytidine (1) exhibited no in vitro antiviral activity at less than or equal to 1 mu M concentration.
• Revankar,G.R.; Robins,R.K., Journal of Heterocyclic Chemistry, 1976, vol. 13, p. 169 - 170
  作者：Revankar,G.R.、Robins,R.K.

  DOI：——

  日期：——