(4R,5R)-4-((tert-butyldimethylsilyl)oxy)-5-(((tert-butyldimethylsilyl)oxy)methyl)-3-bromodihydrofuran-2(3H)-one | 142329-74-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: (4R,5R)-4-((tert-butyldimethylsilyl)oxy)-5-(((tert-butyldimethylsilyl)oxy)methyl)-3-bromodihydrofuran-2(3H)-one
• 英文别名: (4R,5R)-3-bromo-4-[tert-butyl(dimethyl)silyl]oxy-5-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-2-one
• CAS: 142329-74-6；142329-75-7
• 化学式: C₁₇H₃₅BrO₄Si₂
• 分子量: 439.537
• InChiKey: KGJGQUMNPJPYJK-WYAMFQBQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.09
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4R,5R)-4-((tert-butyldimethylsilyl)oxy)-5-(((tert-butyldimethylsilyl)oxy)methyl)-3-bromodihydrofuran-2(3H)-one 在 偶氮二异丁腈 、 溶剂黄146 作用下， 以 四氢呋喃 、 水 、 苯 为溶剂， 反应 122.0h， 生成 2-C-allyl-3-O-tert-butyldimethylsilyl-2-deoxy-D-ribono-1,4-lactone
  参考文献：
  名称：

  Free radical-induced C-allylation of α-bromolactones. Synthesis of 2-C-allyl-2-deoxy-d-arabino-and -d-ribono-1,4-lactones

  摘要：

  Application of the Keck C-allylation of organic halides to 2-bromo-2-deoxy-D-arabinonolactone resulted in the formation of mixtures of 2-C-allyl lactones. The stereochemical preferences observed were dictated by the nature of vicinal and remotely placed substituents in the lactone.

  DOI：

  10.1016/s0008-6215(00)90556-1
• 作为产物：
  描述：

  1-[3,5-bis-O-(tert-butyldimethylsilyl)-2-deoxy-D-erythro-pento-1-enofuranosyl]uracil 在 N-溴代丁二酰亚胺(NBS) 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 以33%的产率得到(4R,5R)-4-((tert-butyldimethylsilyl)oxy)-5-(((tert-butyldimethylsilyl)oxy)methyl)-3-bromodihydrofuran-2(3H)-one
  参考文献：
  名称：

  Anomeric manipulation of nucleosides: Stereosepecific entry to 1′-C-branched uracil nucleosides

  摘要：

  Uracil nucleosides variously branched at die anomeric position have been synthesized through stereoselective bromo-pivaloyloxylation of a 1',2'-unsaturated derivative and successive SnCl4-promoted nucleophilic substitution with organosilicon reagents. This constitutes the first example of C-C bond formation at the anomeric position of nucleoside.

  DOI：

  10.1016/s0040-4039(00)91829-x

文献信息

• Synthesis and anti-HCV activity of β-d-2′-deoxy-2′-α-chloro-2′-β-fluoro and β-d-2′-deoxy-2′-α-bromo-2′-β-fluoro nucleosides and their phosphoramidate prodrugs
  作者：Reuben Ovadia、Ahmed Khalil、Hao Li、Coralie De Schutter、Seema Mengshetti、Shaoman Zhou、Leda Bassit、Steven J. Coats、Franck Amblard、Raymond F. Schinazi

  DOI：10.1016/j.bmc.2019.01.005

  日期：2019.2

  We report herein the synthesis and evaluation of a series of β-d-2'-deoxy-2'-α-chloro-2'-β-fluoro and β-d-2'-deoxy-2'-α-bromo-2'-β-fluoro nucleosides along with their corresponding phosphoramidate prodrugs. Key intermediates, lactols 11 and 12, were obtained by a diastereoselective fluorination of protected 2-deoxy-2-chloro/bromo-ribonolactones 7 and 8. All synthesized nucleosides and prodrugs were evaluated

  我们在此报告一系列β-d-2'-脱氧-2'-α-氯2'-β-氟和β-d-2'-脱氧2'-α-溴-的合成和评价2'-β-氟核苷及其相应的氨基磷酸酯前药。通过保护的2-脱氧-2-氯/溴-核糖内酯内酯7和8的非对映选择性氟化获得了关键中间体乳糖醇11和12。所有合成的核苷和前药均用丙型肝炎病毒（HCV）亚基因组复制子系统进行了评估。
• Divergent and Stereocontrolled Approach to the Synthesis of Uracil Nucleosides Branched at the Anomeric Position
  作者：Yoshiharu Itoh、Kazuhiro Haraguchi、Hiromichi Tanaka、Eisen Gen、Tadashi Miyasaka

  DOI：10.1021/jo00108a031

  日期：1995.2

  Electrophilic addition of NBS/pivalic acid (bromopivaloyloxylation) to 1-[3,5-bis-O-(tert-butyldimethylsilyl)-2-deoxy-D-erythro-pent- 1-enofuranosyl]uracil (2), readily accessible from O-2,2'-anhydro-uridine, furnished 1-[2-bromo-3,5-bis-O-(tert-butyldimethyylsilyl)-2-deoxy-1-(pivaloyloxy)-beta-D-ara-binofuranosyl]uracil (7) stereoselectively. This compound (7), having a leaving group at the 1'-position as well as 2'-beta-Br that could exert anchimeric assistance, serves as versatile intermediate for the stereocontrolled synthesis of various types of 1'-C-branched derivatives through nucleophilic substitutions by the use of organosilicon and organoaluminum reagents. The whole sequence constitutes the first example of the conversion of a naturally-occurring nucleoside to the analogues branched at the anomeric position.
• Diastereocontrolled Electrophilic Fluorinations of 2-Deoxyribonolactone: Syntheses of All Corresponding 2-Deoxy-2-fluorolactones and 2′-Deoxy-2′-fluoro-NAD⁺s
  作者：Yana Cen、Anthony A. Sauve

  DOI：10.1021/jo900637f

  日期：2009.8.21

  Methods to construct 2'-deoxy-2'-fluoro nucleosides have undergone limited improvement in the last 20 years in spite of the substantially increased value of these compounds as pharmaceuticals and as tools for studying biological processes. We herein describe a consolidated approach to synthesize precursors to these commercially and scientifically valuable compounds via diastereocontrolled fluorination of the readily available precursor 2-deoxy-D-ribonolactone. With employment of appropriate sterically bulky silyl protecting groups at the 3 and 5 positions, controlled electrophilic fluorination of the Li-ribonolactone enolate by N-fluorodibenzenesulfonamide yielded the corresponding 2-deoxy-2-fluoroarabinolactone in high isolated yield (72%) The protected 2-deoxy-2,2-difluororibonolactone was obtained similarly in high yield from a second round of electrophilic fluorination (two steps, 51% from protected ribonolactone starting material). Accomplishment of the difficult ribofluorination of the lactone was achieved by the directive effects of a diastereoselectively installed (x-trimethylsilyl group. Electrophilic fluorination of a protected 2-deoxy-2-trimethylsilylarabinolactone via enolate generation provided the protected 2-deoxy-2-fluororibolactone as the exclusive fluorinated product. The reaction also yielded the starting material, the desilylated protected 2-deoxyribonolactone, which was recycled to provide a 38% chemical yield of the fluorinated product (versus initial protected ribonolactone),after consecutive silylation and fluorination cycles. Using our fluorinated sugar precursors, we prepared the 2'-fluoroarabino-, 2'-fluororibo-, and 2',2'-difluoronicotinamide adenine dinucleotides (NAD(+)) of potential biological interest. These syntheses provide the most consolidated and efficient methods for production of sugar precursors of 2'-deoxy-2'-fluoronucleosides and have the advantage of utilizing an air-stable electrophilic fluorinating agent. The fluorinated NAD(+)s are anticipated to be useful for studying a variety of cellular metabolic and signaling processes.