(2R)-5-hydroxy-1,3-oxathiolane-2-carboxylic acid (1R,2S,5R)-5-methyl-2-(1-methylethyl)cyclohexyl ester | 1309459-32-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (2R)-5-hydroxy-1,3-oxathiolane-2-carboxylic acid (1R,2S,5R)-5-methyl-2-(1-methylethyl)cyclohexyl ester
• 英文别名: 5-hydroxy-[1,3]oxathiolane-2-carboxylic acid 2-isopropyl-5-methylcyclohexyl ester；[(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexyl] (2R)-5-hydroxy-1,3-oxathiolane-2-carboxylate
• CAS: 1309459-32-2
• 化学式: C₁₄H₂₄O₄S
• 分子量: 288.408
• InChiKey: KXKDZLRTIFHOHW-YHRKSWLVSA-N

物化性质

• 沸点：
  402.3±45.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  81.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R)-5-hydroxy-1,3-oxathiolane-2-carboxylic acid (1R,2S,5R)-5-methyl-2-(1-methylethyl)cyclohexyl ester 在 甲烷磺酸 、 N,N-二甲基甲酰胺 甲烷磺酸 、 potassium carbonate 、 碘甲烷 作用下， 以 甲醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 32.67h， 生成 5-(4-氨基-2-氧代-2H-嘧啶-1-基)-[1,3]1,3-氧硫杂环戊-2-甲酸孟酯
  参考文献：
  名称：

  [EN] NOVEL PROCESS FOR THE PREPARATION OF CIS-NUCLEOSIDE DERIVATIVE
  [FR] NOVEAU PROCEDE DE PREPARATION DE DERIVE DE CIS-NUCLEOSIDE

  摘要：

  本发明涉及一种改进的过程，用于制备式-1的顺式核苷衍生物，包括将式-2的化合物进行氯化，然后与式-3的化合物在碱的存在下发生反应得到式-4的化合物，将式-4的化合物与烷基卤化物（RiX）反应得到季铵盐，然后与式-5的胞嘧啶衍生物反应得到式-6的化合物，可选择性地去保护式-6的化合物得到式-7的化合物，用金属催化剂在缓冲溶液中还原式-7的化合物，然后加入有机酸得到式-8的化合物，并将式-8的化合物转化为式-1的顺式核苷衍生物。本发明还涉及新型式-8的顺式核苷衍生物。本发明还涉及一种包含式-1的顺式核苷衍生物与赋形剂的药物组合物。

  公开号：

  WO2011095987A1

文献信息

• Synthesis of (±)-Emtricitabine and (±)-Lamivudine by Chlorotrimethylsilane–Sodium Iodide-Promoted Vorbrüggen Glycosylation
  作者：Sarah Jane Mear、Long V. Nguyen、Ashley J. Rochford、Timothy F. Jamison

  DOI：10.1021/acs.joc.1c02772

  日期：2022.3.4

  By simple combination of water and sodium iodide (NaI) with chlorotrimethylsilane (TMSCl), promotion of a Vorbrüggen glycosylation en route to essential HIV drugs emtricitabine (FTC) and lamivudine (3TC) is achieved. TMSCl–NaI in wet solvent (0.1 M water) activates a 1,3-oxathiolanyl acetate donor for N-glycosylation of silylated cytosine derivatives, leading to cis-oxathiolane products with up to

  通过将水和碘化钠 (NaI) 与三甲基氯硅烷 (TMSCl) 简单结合，可以在生产 HIV 基本药物恩曲他滨 (FTC) 和拉米夫定 (3TC) 的途中促进 Vorbrüggen 糖基化。湿溶剂（0.1 M 水）中的 TMSCl–NaI 激活 1,3-氧杂硫杂环戊酯供体，用于甲硅烷基化胞嘧啶衍生物的N-糖基化，从而产生高达 95% 的产率和 >20:1 dr的顺式-氧杂硫杂环戊烷产物。该伸缩序列之后是重结晶和硼氢化物还原，导致从酒石酸二酯快速合成 (±)-FTC/3TC。
• NOVEL PROCESS FOR THE PREPARATION OF CIS-NUCLEOSIDE DERIVATIVE
  申请人：Rama Shankar

  公开号：US20120295930A1

  公开（公告）日：2012-11-22

  The present invention relates to an improved process for the preparation of cis-nucleoside derivative of formula-1 involving chlorination of the compound of formula-2 followed by reaction with compound of formula-3 in presence of a base to get compound of formula-4, reacting the compound of formula-4 with an alkyl halide (RiX) to get a quaternary ammonium salt then with cytosine derivative of formula-5 to provide the compound of formula-6, optionally de-protecting the compound of formula-6 to the compound of formula-7, reducing compound of formula-7 with metal catalyst in presence of a buffer solution, then adding an organic acid to get the compound of formula-8, and converting the compound of formula-8 to cis-nucleoside derivative of formula-1. The present invention further relates to novel cis-nucleoside derivative of formula-8. The present invention also relates to a pharmaceutical composition comprising cis-nucleoside derivative of formula-1 with excipients.
• [EN] NOVEL PROCESS FOR THE PREPARATION OF CIS-NUCLEOSIDE DERIVATIVE<br/>[FR] NOVEAU PROCEDE DE PREPARATION DE DERIVE DE CIS-NUCLEOSIDE
  申请人：MATRIX LAB LTD

  公开号：WO2011095987A1

  公开（公告）日：2011-08-11

  The present invention relates to an improved process for the preparation of cis-nucleoside derivative of formula-1 involving chlorination of the compound of formula-2 followed by reaction with compound of formula-3 in presence of a base to get compound of formula-4, reacting the compound of formula-4 with an alkyl halide (RiX) to get a quaternary ammonium salt then with cytosine derivative of formula-5 to provide the compound of formula-6, optionally de-protecting the compound of formula-6 to the compound of formula-7, reducing compound of formula-7 with metal catalyst in presence of a buffer solution, then adding an organic acid to get the compound of formula-8, and converting the compound of formula-8 to cis-nucleoside derivative of formula-1. The present invention further relates to novel cis-nucleoside derivative of formula-8. The present invention also relates to a pharmaceutical composition comprising cis-nucleoside derivative of formula-1 with excipients.

  本发明涉及一种改进的过程，用于制备式-1的顺式核苷衍生物，包括将式-2的化合物进行氯化，然后与式-3的化合物在碱的存在下发生反应得到式-4的化合物，将式-4的化合物与烷基卤化物（RiX）反应得到季铵盐，然后与式-5的胞嘧啶衍生物反应得到式-6的化合物，可选择性地去保护式-6的化合物得到式-7的化合物，用金属催化剂在缓冲溶液中还原式-7的化合物，然后加入有机酸得到式-8的化合物，并将式-8的化合物转化为式-1的顺式核苷衍生物。本发明还涉及新型式-8的顺式核苷衍生物。本发明还涉及一种包含式-1的顺式核苷衍生物与赋形剂的药物组合物。