1-(2,3-dideoxy-2-fluoro-5-O-trityl-β-D-arabinofuranosyl)cytosine | 128115-04-8

• 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: 1-(2,3-dideoxy-2-fluoro-5-O-trityl-β-D-arabinofuranosyl)cytosine
• 英文别名: 4-amino-1-[(2R,3S,5S)-3-fluoro-5-(trityloxymethyl)oxolan-2-yl]pyrimidin-2-one
• CAS: 128115-04-8
• 化学式: C₂₈H₂₆FN₃O₃
• 分子量: 471.531
• InChiKey: BQONGMMECCSXSY-KYPHJKQUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.46
• 重原子数：
  35.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  79.37
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  1-(2,3-dideoxy-2-fluoro-5-O-trityl-β-D-arabinofuranosyl)cytosine 在 吡啶 、 三氟乙酸 作用下， 以 正丁醇 为溶剂， 生成 [(2S,4S,5R)-5-(4-acetamido-2-oxopyrimidin-1-yl)-4-fluorooxolan-2-yl]methyl acetate
  参考文献：
  名称：

  Synthesis and anti-HIV-1 activity of 2'-"up"-fluoro analogs of active anti-AIDS nucleosides 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (DDC)

  摘要：

  1-(3-Azido-2,3-dideoxy-2-fluoro-beta-D-arabinofuranosyl)thymine (6, F-AZT) and 1-(2,3-dideoxy-2-fluoro-beta-D-threopentofuranosyl)cytosine (12, F-DDC) were synthesized from the potent antiherpes virus nucleosides 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)thymine (1, FMAU) and 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine (FIAC) in the hope that introduction of a 2-"up"-fluoro substituent might potentiate the anti-HIV activity of AZT and DDC. FMAU (1) was converted in three steps into 2,3'-anhydro-1-(2-fluoro-2-deoxy-5-O-trityl-beta-D-lyxofuranosyl)thymine (4), which when treated with NaN3 followed by detritylation afforded 6. F-DDC was prepared by two methods. Tritylation of FIAC followed by treatment of the product with thiocarbonyldimidazole afforded the 5'-O-trityl-3'-O-(imidazolyl)thiocarbonyl nucleoside 9. Upon radical reduction of 9 with Bu3SnH and AIBN, 5'-O-trityl-DDC 10 was obtained. Compound 10 was detritylated to give 12, which (when obtained by this procedure) resisted crystallization, but the diacetate 12' was obtained in crystalline form. Alternatively, FAC (14) was converted into N4,O5'-dibenzoyl derivative 15, which was treated with thiocarbonyldiimidazole. Reduction of 16 with Bu3SnH/AIBN followed by debenzoylation afforded 12, which was obtained in crystalline form. F-AZT did not exhibit any significant activity against the human immunodeficiency virus (HIV) in vitro. F-DDC, however, showed activity against HIV-1, but the therapeutic index is much inferior to that of AZT.

  DOI：

  10.1021/jm00170a016
• 作为产物：
  描述：

  (S,S)-α-fluoro-2,2-dimethyl-1,3-dioxolane-4-propanoic acid methyl ester 在 吡啶 、 盐酸 、 正丙胺 、 三正丁胺 、 二异丁基氢化铝 、 甲基磺酰氯 、 三乙胺 作用下， 以 二氯甲烷 、 氯仿 、 甲苯 为溶剂， -65.0~55.0 ℃ 、8.0 kPa 条件下， 反应 1.75h， 生成 1-(2,3-dideoxy-2-fluoro-5-O-trityl-β-D-arabinofuranosyl)cytosine
  参考文献：
  名称：

  Synthesis of 1-(2,3-dideoxy-2-fluoro-.beta.-D-threo-pentofuranosyl)cytosine (F-ddC). A promising agent for the treatment of acquired immune deficiency syndrome

  摘要：

  A new and practical synthesis of a fluorinated analogue of 2',3'-dideoxycytidine (ddC), 1-(2,3-dideoxy-2-fluoro-beta-D-threo-pentofuranosyl)cytosine (F-ddC), is described. The key feature in the synthesis is the use of the selectively protected 2,4,5-trihydroxypentanoic acid derivative 15 as a chiral pool synthon.

  DOI：

  10.1021/jo00014a013

文献信息

• WATANABE, KYOICHI A.;HARADA, KAZUHO;ZEIDLER, JOANNA;MATULIC-ADAMIC, JASEN+, J. MED. CHEM., 33,(1990) N, C. 2145-2150
  作者：WATANABE, KYOICHI A.、HARADA, KAZUHO、ZEIDLER, JOANNA、MATULIC-ADAMIC, JASEN+

  DOI：——

  日期：——
• OKABE, MASAMI;SUN, RUEN-CHU;ZENCHOFF, GLADYS B., J. ORG. CHEM., 56,(1991) N4, C. 4392-4397
  作者：OKABE, MASAMI、SUN, RUEN-CHU、ZENCHOFF, GLADYS B.

  DOI：——

  日期：——