(3R,6R,6aR)-6-(tert-butoxymethyl)-2,2-dimethyl-5-methylenedihydro-3aH-cyclopenta[d][1,3]-dioxol-4-(5H)one | 1307273-57-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3R,6R,6aR)-6-(tert-butoxymethyl)-2,2-dimethyl-5-methylenedihydro-3aH-cyclopenta[d][1,3]-dioxol-4-(5H)one
• 英文别名: (3aR,6R,6aR)-6-(tert-butoxymethyl)-2,2-dimethyl-5-methylenetetrahydro-4H-cyclopenta-[d][1,3]dioxol-4-one；(2R,3R,4R)-4-(tert-butoxymethyl)-2,3-(isopropylidene-dioxy)-6-(methylenyl)-1-cyclopentanone；(3aR,6R,6aR)-2,2-dimethyl-5-methylidene-6-[(2-methylpropan-2-yl)oxymethyl]-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-one
• CAS: 1307273-57-9
• 化学式: C₁₄H₂₂O₄
• 分子量: 254.326
• InChiKey: SNIAHSMIRVMOMQ-WCQGTBRESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.79
• 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：

  (3R,6R,6aR)-6-(tert-butoxymethyl)-2,2-dimethyl-5-methylenedihydro-3aH-cyclopenta[d][1,3]-dioxol-4-(5H)one 在 cerium(III) chloride heptahydrate 、 三甲基铝 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 72.67h， 生成 (1S,2S,3R,4R)-3-tert-butoxy-4-(tert-butoxymethyl)-5-methylenecyclopenta1,2-diol
  参考文献：
  名称：

  [EN] SYNTHESIS OF 2'-FLUORO-6'-METHYLENE-CARBOCYCLIC ADENOSINE (FMCA) AND 2'-FLUORO-6'-METHYLENE-CARBOCYCLIC GUANOSINE (FMCG)
  [FR] SYNTHÈSE DE L'ADÉNOSINE 2'-FLUORO-6'-MÉTHYLÈNE-CARBOCYCLIQUE (FMCA) ET DE LA GUANOSINE 2'-FLUORO-6'-MÉTHYLÈNE-CARBOCYCLIQUE (FMCG)

  摘要：

  本发明提供了一种新的汇聚方法，用于从易得的起始物质在八个步骤中合成2'-氟-6'-甲基烯基环状腺苷（FMCA）和2'-氟-6'-甲基烯基环状鸟嘌呤（FMCG）。还提供了一种有效且实用的立体特异性制备多用途环状关键中间体（1S,3R,4R）-3-叔丁氧基-4-（叔丁氧甲基）-2-氟-5-亚甲基环戊醇（方案1A或a的化合物8）的方法，仅需六个步骤。还制备了这些化合物的前药。

  公开号：

  WO2017176392A1
• 作为产物：
  描述：

  (3aS,6aR)-2,2-二甲基-4,6a-二氢-3aH-环戊二烯并[d][1,3]二氧杂环戊烯-4-醇 在 manganese(IV) oxide 、 正丁基锂 、 potassium tert-butylate 、 仲丁基锂 、 二异丙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 环己烷 为溶剂， 反应 45.5h， 生成 (3R,6R,6aR)-6-(tert-butoxymethyl)-2,2-dimethyl-5-methylenedihydro-3aH-cyclopenta[d][1,3]-dioxol-4-(5H)one
  参考文献：
  名称：

  仿生异戊烯A和Sterhirsutins A和B的核心骨架的一般仿生杂Diels-Alder方法

  摘要：

  描述了对异戊烯烯A的5,6,11-三环核心骨架，以及甾体素A和B的仿生，区域和立体选择性方法。关键步骤是仿生反电子需求的α-hu草烯和核糖衍生的乙烯基酮的异Diels-Alder环加成电子，然后进行酸催化的1,3-二氧戊环重排，使其与生成的环状烯醇醚相邻。

  DOI：

  10.1021/acs.orglett.8b04003

文献信息

• 2'-Fluoro-6'-Methylene Carbocyclic Nucleosides and Methods of Treating Viral Infections
  申请人：Chu Chung K.

  公开号：US20110244027A1

  公开（公告）日：2011-10-06

  The present invention relates to 2′-Fluoro-6′-methylene carbocyclic nucleosides, pharmaceutical compositions containing these nucleosides and their use in the treatment or prophylaxis of a number of viral infections and secondary disease states and conditions thereof, especially including Hepatitis B virus (HBV) and secondary disease states and conditions thereof (cirrhosis and liver cancer), Heptatitis C virus (HCV), Herpes Simplex virus I and II (HSV-1 and HSV-2), cytomegalovirus (CMV), Varicella-Zoster Virus (VZV) and Epstein Barr virus (EBV) and secondary cancers which occur thereof (lymphoma, nasopharyngeal cancer, including drug resistant (especially including lamivudine and/or adefovir resistant) and other mutant forms of these viruses.

  本发明涉及2'-氟-6'-亚甲基环烷基核苷，以及含有这些核苷的制药组合物及其在治疗或预防多种病毒感染和其次生疾病状态和条件中的应用，特别是包括乙型肝炎病毒（HBV）及其次生疾病状态和条件（肝硬化和肝癌），丙型肝炎病毒（HCV），单纯疱疹病毒I和II（HSV-1和HSV-2），巨细胞病毒（CMV），水痘-带状疱疹病毒（VZV）和EB病毒及其次生癌症（淋巴瘤，鼻咽癌，包括耐拉米夫定和/或阿德福韦耐药的和其他突变形式的这些病毒）。
• Synthesis of 2′-fluoro-6′-methylene-carbocyclic adenosine (FMCA) and 2′-fluoro-6′methylene-carbocyclic guanosine (FMCG)
  申请人：UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.

  公开号：US10995093B2

  公开（公告）日：2021-05-04

  The invention provides a new convergent approach for the synthesis of 2′-fluoro-6′-methylene-carbocyclic adenosine (FMCA) and 2′-fluoro-6′-methylene-carbocyclic guanosine (FMCG) from a readily available starting material in eight steps. An efficient and practical methodology for stereospecific preparation of a versatile carbocyclic key intermediate, (1S,3R, 4R)-3-tert-butoxy-4-(tert-butoxymethyl)-2-fluoro-5-methylenecyclopentanol (compound 8 of scheme 1A or a) in only six (6) steps is also provided. Prodrugs of these compounds are also prepared.

  本发明提供了一种新的聚合方法，从一种容易获得的起始原料出发，通过八个步骤合成 2′-氟-6′-亚甲基碳环腺苷（FMCA）和 2′-氟-6′-亚甲基碳环鸟苷（FMCG）。此外，还提供了一种高效实用的方法，只需六（6）步就能立体特异性地制备多功能碳环关键中间体--(1S,3R,4R)-3-叔丁氧基-4-(叔丁氧甲基)-2-氟-5-亚甲基环戊醇（方案 1A 或 a 中的化合物 8）。还制备了这些化合物的原药。
• Synthesis and antiviral activity of cyclopropyl-spirocarbocyclic adenosine, (4 R ,5 S ,6 R ,7 R )-4-(6-amino-9 H -purin-9-yl)-7-(hydroxymethyl)spiro[2.4]heptane-5,6-diol against hepatitis C virus
  作者：Srinivas Gadthula、Ravindra K. Rawal、Ashoke Sharon、Dong Wu、Brent Korba、Chung K. Chu

  DOI：10.1016/j.bmcl.2011.05.012

  日期：2011.7

  An efficient method was developed for the synthesis of 6-exocyclic methylene carbocyclic intermediate 4. The Simmons-Smith cyclopropanation protocol was applied on the 6-exocyclic methylene of intermediate 4 and demonstrated its utility for the synthesis of novel class of a spiro-carbocyclic nucleoside analog 8. The titled compound 8 demonstrated a significant antiviral activity against HCV with EC(50) values of 0.273 and 0.368 mu M in genotypes 1A and 1B, respectively. (C) 2011 Elsevier Ltd. All rights reserved.
• SYNTHESIS OF 2'-FLUORO-6'-METHYLENE-CARBOCYCLIC ADENOSINE (FMCA) AND 2'-FLUORO-6'-METHYLENE-CARBOCYCLIC GUANOSINE (FMCG)
  申请人：University Of Georgia Research Foundation, Inc.

  公开号：EP3440041B1

  公开（公告）日：2020-11-18
• Synthesis of 2'-Fluoro-6'-Methylene-Carbocyclic Adenosine (FMCA) and 2'-Fluoro-6'Methylene-Carbocyclic Guanosine (FMCG)
  申请人：UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.

  公开号：US20200207770A1

  公开（公告）日：2020-07-02

  The invention provides a new convergent approach for the synthesis of 2′-fluoro-6′-methylene-carbocyclic adenosine (FMCA) and 2′-fluoro-6′-methylene-carbocyclic guanosine (FMCG) from a readily available starting material in eight steps. An efficient and practical methodology for stereospecific preparation of a versatile carbocyclic key intermediate, (1S,3R, 4R)-3-tert-butoxy -4-(tert-butoxymethyl)-2-fluoro-5-methylenecyclopentanol (compound 8 of scheme 1A or a) in only six (6) steps is also provided. Prodrugs of these compounds are also prepared.