2-[(2S,3S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]-2-[(3,4,5-trioctadecoxyphenyl)methyl]butanedioic acid

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 2-[(2S,3S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]-2-[(3,4,5-trioctadecoxyphenyl)methyl]butanedioic acid
• 化学式: C₇₅H₁₃₂N₂O₁₁
• 分子量: 1237.9
• InChiKey: AKSOFCSROKKXCR-NAQUTOIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  26.6
• 重原子数：
  88
• 可旋转键数：
  62
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  181
• 氢给体数：
  4
• 氢受体数：
  11

文献信息

• METHOD FOR PRODUCING OLIGONUCLEOTIDE
  申请人：Ajinomoto Co., Inc.

  公开号：EP2711370A1

  公开（公告）日：2014-03-26

  The problem of the present invention is provision of a method of producing an n+p-mer oligonucleotide efficiently in a high yield, which includes use of, as a starting material, an n-mer oligonucleotide wherein the 3'-terminal hydroxyl group is protected, and the 5'-terminal hydroxyl group is protected by a temporary protecting group, and continuously performing, in a solution, (1) a deprotection step of the 5'-terminal hydroxyl group, (2) a 5'-terminal elongation step by the addition of a p-mer oligonucleotide wherein the 3'-position is phosphoramidited, and (3) an oxidation step or a sulfurization step of a phosphite triester moiety. It has been found that the above-mentioned problem can be solved by adding a particular cation scavenger during the deprotection step, applying a neutralization treatment after completion of the deprotection reaction, and using a particular oxidizing agent or sulfurizing agent in the oxidation step or sulfurization step.

  本发明的问题是提供一种高产率高效生产 n+p-mer 寡核苷酸的方法，该方法包括使用 n-mer 寡核苷酸作为起始材料，其中 3'末端羟基受到保护，5'末端羟基受到临时保护基团的保护、在溶液中连续进行以下步骤：(1) 5'末端羟基的去保护步骤；(2) 通过添加 p-聚合寡核苷酸进行 5'末端延伸步骤，其中 3'位被磷酸化；(3) 亚磷酸三酯分子的氧化步骤或硫化步骤。 研究发现，在脱保护步骤中加入特定的阳离子清除剂，在脱保护反应完成后进行中和处理，以及在氧化步骤或硫化步骤中使用特定的氧化剂或硫化剂，可以解决上述问题。
• OLIGONUCLEOTIDE PRODUCTION METHOD, AND NUCLEOSIDE, NUCLEOTIDE, OR OLIGONUCLEOTIDE
  申请人：AJINOMOTO CO., INC.

  公开号：EP3398955A1

  公开（公告）日：2018-11-07

  The present invention provides a production method oligonucleotide, including (1) a step of condensing a nucleoside, nucleotide or oligonucleotide (a) or the like wherein a 5'-hydroxy group is not protected and a nucleoside, nucleotide or oligonucleotide (b) wherein a 5'-hydroxy group is protected in a non-polar solvent to give a reaction solution containing a phosphite triester product (c); (3) a step of oxidizing or sulfurizing the phosphite triester product (c) to give a reaction solution containing an oligonucleotide (d) wherein the 5'-hydroxy group is protected; (4) a step of deprotecting the oligonucleotide (d) to give a reaction solution containing an oligonucleotide (e) wherein the 5'-hydroxy group is not protected; and (6) a step of adding a polar solvent to the reaction solution containing the oligonucleotide (e) and purifying the oligonucleotide (e) by solid-liquid separation or extraction.

  本发明提供了一种寡核苷酸的生产方法，包括：(1)在非极性溶剂中缩合5'-羟基未被保护的核苷、核苷酸或寡核苷酸(a)或类似物和5'-羟基被保护的核苷、核苷酸或寡核苷酸(b)，得到含有亚磷酸三酯产物(c)的反应溶液；(2)在非极性溶剂中缩合5'-羟基被保护的核苷、核苷酸或寡核苷酸(b)，得到含有亚磷酸三酯产物(c)的反应溶液；(3) 对亚磷酸三酯产物（c）进行氧化或硫化，得到含有寡核苷酸（d）的反应溶液，其中 5'- 羟基被保护； (4) 对寡核苷酸（d）进行脱保护，得到含有寡核苷酸（e）的反应溶液，其中 5'- 羟基未被保护；(6) 向含有寡核苷酸（e）的反应溶液中加入极性溶剂，并通过固液分离或萃取纯化寡核苷酸（e）。
• METHOD FOR PRODUCING OLIGONUCLEOTIDES
  申请人：AJINOMOTO CO., INC.

  公开号：EP2711370B1

  公开（公告）日：2018-01-03