(D-erythro,D-threo)-2-deoxy-2,2-difluoropentofuranos-1-ulose-3-benzoate | 122111-07-3

• 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: (D-erythro,D-threo)-2-deoxy-2,2-difluoropentofuranos-1-ulose-3-benzoate
• 英文别名: [(2R)-4,4-difluoro-2-(hydroxymethyl)-5-oxooxolan-3-yl] benzoate
• CAS: 122111-07-3；122111-08-4
• 化学式: C₁₂H₁₀F₂O₅
• 分子量: 272.205
• InChiKey: BIFWGBBUNCUGII-VEDVMXKPSA-N

物化性质

• 沸点：
  343.7±42.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  苯甲酰氯 、 (D-erythro,D-threo)-2-deoxy-2,2-difluoropentofuranos-1-ulose-3-benzoate 在 吡啶 、 4-二甲氨基吡啶 作用下， 以 乙酸乙酯 为溶剂， 反应 2.0h， 以100%的产率得到(D-erythro,D-threo)-2-deoxy-2,2-difluoropentofuranos-1-ulose-3,5-dibenzoate
  参考文献：
  名称：

  Stereospecific Synthesis of 2-Deoxy-2,2-difluororibonolactone and Its Use in the Preparation of 2′-Deoxy-2′,2′-difluoro-β-D-ribofuranosyl Pyrimidine Nucleosides: The Key Role of Selective Crystallization

  摘要：

  本文描述了潜在抗癌药物2′-脱氧-2′,2′-二氟胞苷（吉西他滨）的立体特异性合成。通过两次非对映选择性结晶实现了立体选择性：即关键中间体二氟乳糖内酯2a的结晶，以及从异头混合物中结晶出吉西他滨的盐酸盐16b。由于2a可以大量获得，因此合成了其他2′-脱氧-2′,2′-二氟嘧啶核苷，如2′-脱氧-2′,2′-二氟尿苷（19），用于结构-活性关系研究。

  DOI：

  10.1055/s-1992-26167
• 作为产物：
  描述：

  3-(2,2-二甲基-1,3-二氧戊环-4-基)-2,2-二氟-3-羟基丙酸乙酯 在 4-二甲氨基吡啶 2,6-二甲基吡啶 、 水 、 甲苯 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 (D-erythro,D-threo)-2-deoxy-2,2-difluoropentofuranos-1-ulose-3-benzoate
  参考文献：
  名称：

  Stereospecific Synthesis of 2-Deoxy-2,2-difluororibonolactone and Its Use in the Preparation of 2′-Deoxy-2′,2′-difluoro-β-D-ribofuranosyl Pyrimidine Nucleosides: The Key Role of Selective Crystallization

  摘要：

  本文描述了潜在抗癌药物2′-脱氧-2′,2′-二氟胞苷（吉西他滨）的立体特异性合成。通过两次非对映选择性结晶实现了立体选择性：即关键中间体二氟乳糖内酯2a的结晶，以及从异头混合物中结晶出吉西他滨的盐酸盐16b。由于2a可以大量获得，因此合成了其他2′-脱氧-2′,2′-二氟嘧啶核苷，如2′-脱氧-2′,2′-二氟尿苷（19），用于结构-活性关系研究。

  DOI：

  10.1055/s-1992-26167

文献信息

• Process for Preparing Gemcitabine and Associated Intermediates
  申请人：Naddaka Vladimir

  公开号：US20070191598A1

  公开（公告）日：2007-08-16

  The present invention provides processes for preparing novel chemical substances that are useful as intermediates in the preparation of gemcitabine and processes for preparing gemcitabine therewith. Exemplary intermediates include mixtures of D-erythro and D-threo (3R- and 3S-) isomers of 3-(hydroxy)-2,2-difluoro-3-(2,2-dimethyldioxolan-4-yl)propionic acid salts. Also provided is a novel process for selectively isolating the D-erythro and D-threo isomers of the said salts in purities of at least about 95%, and processes of using them for preparing nucleoside analogs such as, e.g., gemcitabine and intermediates and analogs thereof.

  本发明提供了用于制备新型化学物质的方法，这些化学物质可作为吉西他滨制备过程中的中间体，并提供了与之一起制备吉西他滨的方法。示例中间体包括3-(羟基)-2,2-二氟-3-(2,2-二甲基二氧杂环戊酮-4-基)丙酸盐的D-erythro和D-threo（3R-和3S-）异构体的混合物。还提供了一种新型方法，用于选择性地分离所述盐的D-erythro和D-threo异构体，其纯度至少约为95％，以及使用它们制备类似核苷类似物（例如吉西他滨及其中间体和类似物）的方法。
• PROCESS FOR PREPARING GEMCITABINE AND ASSOCIATED INTERMEDIATES
  申请人：Naddaka Vladimir

  公开号：US20070249823A1

  公开（公告）日：2007-10-25

  The present invention provides novel intermediates, which preferably include 3-substituted, alkyl 2,2-difluoro-3-hydroxy-3-(2,2-dialkyldioxolan-4-yl)-propionate derivatives, and 3,5-disubstituted-2-deoxy-2,2-difluoro-1-oxo-D-ribose derivatives. The present invention also provides processes for producing such intermediates and processes for producing gemcitabine therewith.

  本发明提供了新颖的中间体，其中包括3-取代的烷基2,2-二氟-3-羟基-3-(2,2-二烷基二氧杂环戊酮-4-基)-丙酸酯衍生物，以及3,5-二取代-2-脱氧-2,2-二氟-1-氧代-D-核糖衍生物。本发明还提供了生产这种中间体的方法以及生产吉西他滨的方法。
• GEMCITABINE PRODUCTION PROCESS
  申请人：ZELIKOVITCH Lior

  公开号：US20080262215A1

  公开（公告）日：2008-10-23

  Provided is a process for preparing gemcitabine or a salt thereof, which preferably includes selectively precipitating the β-anomer of a 3′,5′-di-O-protected-N 4 -trimethylsilyl-2′-deoxy-2′,2′-difluorocytidine, removing the protecting groups to produce gemcitabine, and, optionally, converting the gemcitabine into a salt. Preferably, the 3′ and 5′ protecting groups are the same or different, and at least one of the 3′ and 5′ protecting groups is cinnamoyl, naphthoyl, naphthylmethylcarbonyl, 2-methylbenzylcarbonyl, 4-methylbenzylcarbonyl or 9-fluorenylmethyloxycarbonyl. Also provided are methods for enriching the β-anomer from an anomeric mixture of a 3′,5′-di-O-protected-N 4 -trimethylsilyl-2′-deoxy-2′,2′-difluorocytidine, e.g., a N 4 -trimethylsilyl-2′-deoxy-2′,2′-difluoro-cytidine-3′,5′-diester, e.g., 3′,5′-dicinnamoyl-N 4 -trimethylsilyl-2′-deoxy-2′,2′-difluorocytidine, using a slurrying process, and methods for converting the β-anomer-enriched product into gemcitabine or a salt thereof.

  提供了一种制备吉西他滨或其盐的过程，其优选包括选择性沉淀3′，5′-二保护-N4-三甲基硅基-2′-脱氧-2′，2′-二氟胞苷的β-异构体，去除保护基以产生吉西他滨，并可将吉西他滨转化为盐。优选地，3′和5′保护基相同或不同，并且3′和5′保护基中至少有一个是肉桂酰基，萘酰基，萘基甲基羰基，2-甲基苄基羰基，4-甲基苄基羰基或9-芴基甲氧羰基。还提供了一种使用搅拌法从3′，5′-二保护-N4-三甲基硅基-2′-脱氧-2′，2′-二氟胞苷的异构体混合物，例如N4-三甲基硅基-2′-脱氧-2′，2′-二氟胞苷-3′，5′-二酯，例如3′，5′-二肉桂酰基-N4-三甲基硅基-2′-脱氧-2′，2′-二氟胞苷，使用混悬过程富集β-异构体的方法，以及将富集β-异构体的产物转化为吉西他滨或其盐的方法。
• Method for the Preparation of D-Erythro-2,2-Difluoro-2-Deoxy-1-Oxoribose Derivative
  申请人：Lee Jaeheon

  公开号：US20080058509A1

  公开（公告）日：2008-03-06

  3R-carboxylate enantiomer derivative of formula (III) can be prepared easily and selectively by the method of the present invention, and a highly pure D-erythro-2,2-difluoro-2-deoxy-1-oxoribose derivative can be prepared efficiently from the compound of formula (III) as an intermediate.
• PROCESS FOR PREPARING OF 2'-DEOXY-2'2'-DIFLUOROCYTIDINE
  申请人：Park Su-Jin

  公开号：US20100069625A1

  公开（公告）日：2010-03-18

  Disclosed is a method for preparing 2′-deoxy-2′,2′-difluorocytidine of Formula I comprising, preparing an optically pure 3R-hydroxypropane amide compound of Formula VIII from an optical ester compound of Formula IX using an optically active chiral amine, preparing an optically pure D-erythro-2,2-difluoro-2-deoxy-1-oxoribose compound of Formula V from the compound of Formula VIII, glycosylating the compound of Formula V with a nucleobase to prepare the 2′-deoxy-2′,2′-difluorocytidine of Formula I as a β-nucleoside. With the present invention, it is possible to prepare an optically pure compound of Formula I in a high purity and a high yield. In the Formulae, R 1 and R 2 are protecting groups and are each independently benzoyl, 4-methylbenzoyl, 3-methylbenzoyl, 4-cyanobenzoyl, 3-cyanobenzoyl, 4-propylbenzoyl, 2-ethoxybenzoyl, 4-t-butylbenzoyl, 1-naphthoyl or 2-naphthoyl, R 3 , R 4 and R 7 are each independently C 1 -C 3 alkyl, R 5 is methyl or ethyl, R 6 is hydrogen, methyl or methoxy.