[P(R)]-S^P-[2-cyano-2-(hydroxymethyl)-3-methoxy-3-oxopropyl]thymidylyl-(3'-> 5')-thymidine | 477530-22-6

• 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: [P(R)]-S^P-[2-cyano-2-(hydroxymethyl)-3-methoxy-3-oxopropyl]thymidylyl-(3'-> 5')-thymidine
• CAS: 477530-22-6
• 化学式: C₂₆H₃₄N₅O₁₄PS
• 分子量: 703.621
• InChiKey: QXNCKCOORVURSU-DNMPCYAJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.45
• 重原子数：
  47.0
• 可旋转键数：
  13.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  274.49
• 氢给体数：
  5.0
• 氢受体数：
  18.0

反应信息

• 作为反应物：
  描述：

  [P(R)]-S^P-[2-cyano-2-(hydroxymethyl)-3-methoxy-3-oxopropyl]thymidylyl-(3'-> 5')-thymidine 在 hydroxide 作用下， 以 水 为溶剂， 生成 ammonium thymidin-3'-yl thymidin-5'-yl (R)-phosphorothioate
  参考文献：
  名称：

  Towards Nucleotide Prodrugs Derived from 2,2-Bis(hydroxymethyl)malonate and Its Congeners: Hydrolytic Cleavage of 2-Cyano-2-(hydroxymethyl)-3-methoxy-3-oxopropyl and 3-(Alkylamino)-2-cyano-2-(hydroxymethyl)-3-oxopropyl Protections from the Internucleosidic Phosphodiester and Phosphorothioate Linkages

  摘要：

  Thymidylyl-(3'-->5')-thymidine (TpT) and its stereoisomeric phosphoromonothioate analogs [P(R)]- and [P(S)]-Tp(s)T having the phosphate or thiophosphate linkage protected with a 2-cyano-2-{[(4,4'-dimethoxy-trityl)oxy]methyl}-3-methoxy-3-oxopropyl group (see 5a,b), as well as [P(R)]-Tp(s)T bearing a S-(2-cyano-2-{[(4,4'-dimethoxytrityl)oxy]methyl}-3-oxo-3-[(2-phenylethyl)amino]propyl) protection (see 5c), were prepared. ne kinetics of the cleavage of the protecting group from the corresponding detritylated compounds 6a-c was studied over a pH range from 2 to 7. All compounds undergo a hydroxide-ion-catalyzed reaction that releases the unprotected TpT (7a) or Tp(s)T (7b), in all likelihood by departure of the hydroxymethyl group as formaldehyde and concomitant elimination of the phosphodiester or phosphorothioate from the resulting carbanion. The half-life for the deprotection of 6a and 6b is ca. 6 s at pH 7 and 25degrees, and that of 6c ca. 600 s. The reasonably fast release of Tp(s)T from 6c offers a novel method for temporary intrachain attachment of peptides to oligonucleotides to enhance the cellular uptake.

  DOI：

  10.1002/1522-2675(200207)85:7<1869::aid-hlca1869>3.0.co;2-w
• 作为产物：
  描述：

  2-氰基-3-羟基-2-(羟甲基)丙酸甲酯 在 吡啶 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 24.2h， 生成 [P(R)]-S^P-[2-cyano-2-(hydroxymethyl)-3-methoxy-3-oxopropyl]thymidylyl-(3'-> 5')-thymidine
  参考文献：
  名称：

  Towards Nucleotide Prodrugs Derived from 2,2-Bis(hydroxymethyl)malonate and Its Congeners: Hydrolytic Cleavage of 2-Cyano-2-(hydroxymethyl)-3-methoxy-3-oxopropyl and 3-(Alkylamino)-2-cyano-2-(hydroxymethyl)-3-oxopropyl Protections from the Internucleosidic Phosphodiester and Phosphorothioate Linkages

  摘要：

  Thymidylyl-(3'-->5')-thymidine (TpT) and its stereoisomeric phosphoromonothioate analogs [P(R)]- and [P(S)]-Tp(s)T having the phosphate or thiophosphate linkage protected with a 2-cyano-2-{[(4,4'-dimethoxy-trityl)oxy]methyl}-3-methoxy-3-oxopropyl group (see 5a,b), as well as [P(R)]-Tp(s)T bearing a S-(2-cyano-2-{[(4,4'-dimethoxytrityl)oxy]methyl}-3-oxo-3-[(2-phenylethyl)amino]propyl) protection (see 5c), were prepared. ne kinetics of the cleavage of the protecting group from the corresponding detritylated compounds 6a-c was studied over a pH range from 2 to 7. All compounds undergo a hydroxide-ion-catalyzed reaction that releases the unprotected TpT (7a) or Tp(s)T (7b), in all likelihood by departure of the hydroxymethyl group as formaldehyde and concomitant elimination of the phosphodiester or phosphorothioate from the resulting carbanion. The half-life for the deprotection of 6a and 6b is ca. 6 s at pH 7 and 25degrees, and that of 6c ca. 600 s. The reasonably fast release of Tp(s)T from 6c offers a novel method for temporary intrachain attachment of peptides to oligonucleotides to enhance the cellular uptake.

  DOI：

  10.1002/1522-2675(200207)85:7<1869::aid-hlca1869>3.0.co;2-w