[2-(2,2,2-Trifluoro-acetylamino)-ethyl]-carbamic acid 2-[(2R,3S,5R)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-3-hydroxy-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-2-yl]-ethyl ester | 203200-36-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: [2-(2,2,2-Trifluoro-acetylamino)-ethyl]-carbamic acid 2-[(2R,3S,5R)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-3-hydroxy-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-2-yl]-ethyl ester
• 英文别名: 2-[(2R,3S,5R)-2-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]ethyl N-[2-[(2,2,2-trifluoroacetyl)amino]ethyl]carbamate
• CAS: 203200-36-6
• 化学式: C₃₈H₄₁F₃N₄O₁₀
• 分子量: 770.76
• InChiKey: DDSQSZGDEQBBLQ-WWEBLFKJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  55
• 可旋转键数：
  16
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  174
• 氢给体数：
  4
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  2-氰乙基N,N-二异丙基氯亚磷酰胺 、 [2-(2,2,2-Trifluoro-acetylamino)-ethyl]-carbamic acid 2-[(2R,3S,5R)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-3-hydroxy-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-2-yl]-ethyl ester 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以72%的产率得到2-[(2R,3S,5R)-2-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-3-[2-cyanoethoxy-[di(propan-2-yl)amino]phosphanyl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]ethyl N-[2-[(2,2,2-trifluoroacetyl)amino]ethyl]carbamate
  参考文献：
  名称：

  Nucleosides and Nucleotides. 174. Synthesis of Oligodeoxynucleotides Containing 4‘-C-[2-[[N-(2-Aminoethyl)carbamoyl]oxy]ethyl]thymidine and Their Thermal Stability and Nuclease-Resistance Properties¹

  摘要：

  The synthesis and properties of oligodeoxynucleotides (ODNs) containing 4'-C-[2-[IN-(2-aminoethyl)carbamoyl]oxy]ethyl]thymidine (3) are described. 4'alpha-(2-Hydroxyethyl)thymidine (4), which is a precursor for phosphoramidite 5, was synthesized using a newly developed intramolecular radical cyclization reaction at the 4'-position of thymidine derivative 7. The radical reaction of 4'beta-(phenylseleno)-3'-O- (dimethylvinylsilyl)thymidine derivative 7, which was prepared from thymidine in several steps, with Bu3SnH and AIBN, followed by Tamao oxidation, gave either 4'alpha-(2-hydroxyethyl) derivative 6 or 4'alpha-(1-hydroxyethyl) derivative 13, respectively. With a low Bu-3-SnH concentration, the reaction gave 6, via. 6-endo-radical-cyclized product 11, as a sole product in 87% yield. The reaction of 7 in the presence of excess Bu3SnH gave 13 in 75% yield, via 5-exo-cyclized product 12, as a diastereomeric mixture. The 4'alpha-(2-hydroxyethyl) derivative 6 was then converted into a 4'-C-[2-[IN-(2-aminoethyl)carbamoyl]oxy]ethyl]thymidine derivative 14, which was phosphitylated to give phosphoramidite 5 in 72% yield. In this study, 3 was incorporated into a nonadecamer, d[CTGGCTCAGCTCGTCTCAT]-3', and a heptadecamer, d[CTCGTACCATTCCGCTC]-3', instead of T at various positions. ODNs containing 3 were more resistant to nucleolytic hydrolysis by both snake venom phosphodiesterase (a 3'-exonuclease) and DNase I (an endonuclease) than unmodified parent ODNs, although ODNs containing 3 only slightly destabilized duplex formation with both complementary DNA and RNA strands. Furthermore, the duplex formed by an ODN containing 3 and its complementary RNA was a good substrate for Escherichia coli RNase H.

  DOI：

  10.1021/jo9720492
• 作为产物：
  描述：

  5'-O-(dimethoxytrityl)-4'-C-(2-hydroxyethyl)thymidine 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 [2-(2,2,2-Trifluoro-acetylamino)-ethyl]-carbamic acid 2-[(2R,3S,5R)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-3-hydroxy-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-2-yl]-ethyl ester
  参考文献：
  名称：

  Nucleosides and Nucleotides. 174. Synthesis of Oligodeoxynucleotides Containing 4‘-C-[2-[[N-(2-Aminoethyl)carbamoyl]oxy]ethyl]thymidine and Their Thermal Stability and Nuclease-Resistance Properties¹

  摘要：

  The synthesis and properties of oligodeoxynucleotides (ODNs) containing 4'-C-[2-[IN-(2-aminoethyl)carbamoyl]oxy]ethyl]thymidine (3) are described. 4'alpha-(2-Hydroxyethyl)thymidine (4), which is a precursor for phosphoramidite 5, was synthesized using a newly developed intramolecular radical cyclization reaction at the 4'-position of thymidine derivative 7. The radical reaction of 4'beta-(phenylseleno)-3'-O- (dimethylvinylsilyl)thymidine derivative 7, which was prepared from thymidine in several steps, with Bu3SnH and AIBN, followed by Tamao oxidation, gave either 4'alpha-(2-hydroxyethyl) derivative 6 or 4'alpha-(1-hydroxyethyl) derivative 13, respectively. With a low Bu-3-SnH concentration, the reaction gave 6, via. 6-endo-radical-cyclized product 11, as a sole product in 87% yield. The reaction of 7 in the presence of excess Bu3SnH gave 13 in 75% yield, via 5-exo-cyclized product 12, as a diastereomeric mixture. The 4'alpha-(2-hydroxyethyl) derivative 6 was then converted into a 4'-C-[2-[IN-(2-aminoethyl)carbamoyl]oxy]ethyl]thymidine derivative 14, which was phosphitylated to give phosphoramidite 5 in 72% yield. In this study, 3 was incorporated into a nonadecamer, d[CTGGCTCAGCTCGTCTCAT]-3', and a heptadecamer, d[CTCGTACCATTCCGCTC]-3', instead of T at various positions. ODNs containing 3 were more resistant to nucleolytic hydrolysis by both snake venom phosphodiesterase (a 3'-exonuclease) and DNase I (an endonuclease) than unmodified parent ODNs, although ODNs containing 3 only slightly destabilized duplex formation with both complementary DNA and RNA strands. Furthermore, the duplex formed by an ODN containing 3 and its complementary RNA was a good substrate for Escherichia coli RNase H.

  DOI：

  10.1021/jo9720492

文献信息

• Nucleosides and Nucleotides. 174. Synthesis of Oligodeoxynucleotides Containing 4‘-<i>C</i>-[2-[[<i>N</i>-(2-Aminoethyl)carbamoyl]oxy]ethyl]thymidine and Their Thermal Stability and Nuclease-Resistance Properties¹
  作者：Yoshihito Ueno、Yuki Nagasawa、Isamu Sugimoto、Naoshi Kojima、Makiko Kanazaki、Satoshi Shuto、Akira Matsuda

  DOI：10.1021/jo9720492

  日期：1998.3.1

  The synthesis and properties of oligodeoxynucleotides (ODNs) containing 4'-C-[2-[IN-(2-aminoethyl)carbamoyl]oxy]ethyl]thymidine (3) are described. 4'alpha-(2-Hydroxyethyl)thymidine (4), which is a precursor for phosphoramidite 5, was synthesized using a newly developed intramolecular radical cyclization reaction at the 4'-position of thymidine derivative 7. The radical reaction of 4'beta-(phenylseleno)-3'-O- (dimethylvinylsilyl)thymidine derivative 7, which was prepared from thymidine in several steps, with Bu3SnH and AIBN, followed by Tamao oxidation, gave either 4'alpha-(2-hydroxyethyl) derivative 6 or 4'alpha-(1-hydroxyethyl) derivative 13, respectively. With a low Bu-3-SnH concentration, the reaction gave 6, via. 6-endo-radical-cyclized product 11, as a sole product in 87% yield. The reaction of 7 in the presence of excess Bu3SnH gave 13 in 75% yield, via 5-exo-cyclized product 12, as a diastereomeric mixture. The 4'alpha-(2-hydroxyethyl) derivative 6 was then converted into a 4'-C-[2-[IN-(2-aminoethyl)carbamoyl]oxy]ethyl]thymidine derivative 14, which was phosphitylated to give phosphoramidite 5 in 72% yield. In this study, 3 was incorporated into a nonadecamer, d[CTGGCTCAGCTCGTCTCAT]-3', and a heptadecamer, d[CTCGTACCATTCCGCTC]-3', instead of T at various positions. ODNs containing 3 were more resistant to nucleolytic hydrolysis by both snake venom phosphodiesterase (a 3'-exonuclease) and DNase I (an endonuclease) than unmodified parent ODNs, although ODNs containing 3 only slightly destabilized duplex formation with both complementary DNA and RNA strands. Furthermore, the duplex formed by an ODN containing 3 and its complementary RNA was a good substrate for Escherichia coli RNase H.