5'-O-(dimethoxytrityl)-4'-C-(2-hydroxyethyl)thymidine | 203200-35-5

• 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: 5'-O-(dimethoxytrityl)-4'-C-(2-hydroxyethyl)thymidine
• 英文别名: 1-[(2R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-hydroxy-5-(2-hydroxyethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 203200-35-5
• 化学式: C₃₃H₃₆N₂O₈
• 分子量: 588.657
• InChiKey: ITVGDNXIRQVJOU-NPLMNSEMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  43
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  127
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5'-O-(dimethoxytrityl)-4'-C-(2-hydroxyethyl)thymidine 在 10percent Pd/C 4-二甲氨基吡啶 、 sodium azide 、 四丁基氟化铵 、 氢气 、 potassium carbonate 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， -78.0~20.0 ℃ 、101.33 kPa 条件下， 反应 7.67h， 生成 5'-O-(dimethoxytrityl)-4'-C-[2-(N-trifluoroacetyl)aminoethyl]thymidine
  参考文献：
  名称：

  Highly Nuclease-Resistant Phosphodiester-Type Oligodeoxynucleotides Containing 4‘α-C-Aminoalkylthymidines Form Thermally Stable Duplexes with DNA and RNA. A Candidate for Potent Antisense Molecules

  摘要：

  The properties of phosphodiester oligodeoxynucleotides (ODNs) containing 4'alpha-C-aminomethyl, -ethyl, -propyl, and -N-(2-aminoethyl)carbamoylthymidines (1, 2, 4, and 5) as potential antisense molecules are investigated in detail. We developed new radical chemistry with a vinylsilyl or an allylsilyl;I group as a temporary radical acceptor tether to synthesize the required 4'alpha-branched thymidines. Thus, an intramolecular radical cyclization of 4'-phenylseleno nucleosides 7a and 7b, which have a dimethylvinylsilyl and a dimethylallylsilyl group at the 3'-hydroxyl, respectively, with Bu3SnH/AIBN and subsequent Tamao oxidation provided 5'-O-[dimethoxytrityl(DMTr)]-4'alpha-C-(2-hydroxyethyl)thymidine (8a) and 5'-O-DMTr-4'alpha-C-(3-hydroxypropyl)thymidine (8b). Compounds 8a and 8b were then converted into 4'alpha-C-(2-trifluoroacetamidoethyl)thymidine 12a and 4'alpha-C-(3-trifluoroacetamidopropyl)thymid 12b, which were phosphitylated to give the phosphoramidite units 14a and 14b. The phosphoramidite units of 1 and 5 were prepared by previous methods. The nucleosides 1, 2, 1, and 5 were incorporated into the 18-mer, 5'-d[MTMTMTMTMTMTMTMTMT]-3' where M is 5-methyl-2'-deoxycytidine, instead of T at various positions. We also prepared a 21-mer ODN 29 with a mixed sequence containing five residues of 2. The ODNs containing the modified nucleosides formed more stable duplexes with complementary DNA than the corresponding unmodified ODN. These ODNs also formed stable duplexes with the complimentary RNA, The ODNs containing the modified nucleosides were significantly resistant to nucleolytic hydrolysis by both snake venom phosphodiesterase (a 3'-exonuclease) and DNase 1 (an endonuclease) and were also very stable in PBS containing 50% human serum. It is worthwhile to note that these ODNs contain natural phosphodiester linkages. Furthermore, the duplexes formed by the ODNs containing the modified nucleosides and their complementary RNAs were good substrates for Escherichia coli RNase H and HeLa cell nuclear extracts as a source of human RNase H. Thus. these ODNs were identified as candidates for antisense molecules.

  DOI：

  10.1021/ja9934706
• 作为产物：
  描述：

  1-[(2R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-hydroxy-5-phenylselanyloxolan-2-yl]-5-methylpyrimidine-2,4-dione 在 4-二甲氨基吡啶 、 potassium fluoride 、 偶氮二异丁腈 、 双氧水 、 三正丁基氢锡 、 potassium hydrogencarbonate 、 三乙胺 作用下， 以 苯 为溶剂， 生成 5'-O-(dimethoxytrityl)-4'-C-(2-hydroxyethyl)thymidine
  参考文献：
  名称：

  Synthesis of Oligodeoxynucleotides Containing 4′-C-Aminoalkyl-thymidines and Their Thermal Stability and Nuclease-Resistance Properties

  摘要：

  To find the nuclease-resistant oligodeoxynucleotides (ODNs) with natural phosphodiester linkages, we designed and synthesized ODNs containing 4'-C-aminoalkylthymidines (1-4). We found that the ODNs containing 1, 2, 3 or 4 were more resistant to nucleolytic hydrolysis by both snake venom phosphodiesterase (a 3'-exonuclease) and DNase I (an endonuclease) than unmodified ODNs.

  DOI：

  10.1080/07328319908044731

文献信息

• Nucleosides and nucleotides. 183. Synthesis of 4′ α-branched thymidines as a new type of antiviral agent
  作者：Isamu Sugimoto、Satoshi Shuto、Shuichi Mori、Shiro Shigeta、Akira Matsuda

  DOI：10.1016/s0960-894x(99)00010-4

  日期：1999.2

  A series of 4'alpha-branched thymidines was synthesized and evaluated as potential antiviral agents. 4'-Ethylthymidine (3), 4'-ethenylthymidine (5), and 4'-ethynylthymidine (6) exhibited potent anti-HSV-1 and anti-HIV-1 activities with no significant cytotoxicity.

  合成了一系列的4'α-支化胸腺嘧啶核苷，并将其评估为潜在的抗病毒药。4'-乙基胸苷（3），4'-乙烯基胸苷（5）和4'-乙炔基胸腺嘧啶（6）表现出有效的抗HSV-1和抗HIV-1活性，且无明显细胞毒性。
• Synthesis of Oligodeoxynucleotides Containing 4′-<i>C</i>-Aminoalkyl-thymidines and Their Thermal Stability and Nuclease-Resistance Properties
  作者：Yoshihito Ueno、Makiko Kanazaki、Satoshi Shuto、Akira Matsuda

  DOI：10.1080/07328319908044731

  日期：1999.6

  To find the nuclease-resistant oligodeoxynucleotides (ODNs) with natural phosphodiester linkages, we designed and synthesized ODNs containing 4'-C-aminoalkylthymidines (1-4). We found that the ODNs containing 1, 2, 3 or 4 were more resistant to nucleolytic hydrolysis by both snake venom phosphodiesterase (a 3'-exonuclease) and DNase I (an endonuclease) than unmodified ODNs.
• 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.
• Highly Nuclease-Resistant Phosphodiester-Type Oligodeoxynucleotides Containing 4‘α-<i>C</i>-Aminoalkylthymidines Form Thermally Stable Duplexes with DNA and RNA. A Candidate for Potent Antisense Molecules
  作者：Makiko Kanazaki、Yoshihito Ueno、Satoshi Shuto、Akira Matsuda

  DOI：10.1021/ja9934706

  日期：2000.3.1

  The properties of phosphodiester oligodeoxynucleotides (ODNs) containing 4'alpha-C-aminomethyl, -ethyl, -propyl, and -N-(2-aminoethyl)carbamoylthymidines (1, 2, 4, and 5) as potential antisense molecules are investigated in detail. We developed new radical chemistry with a vinylsilyl or an allylsilyl;I group as a temporary radical acceptor tether to synthesize the required 4'alpha-branched thymidines. Thus, an intramolecular radical cyclization of 4'-phenylseleno nucleosides 7a and 7b, which have a dimethylvinylsilyl and a dimethylallylsilyl group at the 3'-hydroxyl, respectively, with Bu3SnH/AIBN and subsequent Tamao oxidation provided 5'-O-[dimethoxytrityl(DMTr)]-4'alpha-C-(2-hydroxyethyl)thymidine (8a) and 5'-O-DMTr-4'alpha-C-(3-hydroxypropyl)thymidine (8b). Compounds 8a and 8b were then converted into 4'alpha-C-(2-trifluoroacetamidoethyl)thymidine 12a and 4'alpha-C-(3-trifluoroacetamidopropyl)thymid 12b, which were phosphitylated to give the phosphoramidite units 14a and 14b. The phosphoramidite units of 1 and 5 were prepared by previous methods. The nucleosides 1, 2, 1, and 5 were incorporated into the 18-mer, 5'-d[MTMTMTMTMTMTMTMTMT]-3' where M is 5-methyl-2'-deoxycytidine, instead of T at various positions. We also prepared a 21-mer ODN 29 with a mixed sequence containing five residues of 2. The ODNs containing the modified nucleosides formed more stable duplexes with complementary DNA than the corresponding unmodified ODN. These ODNs also formed stable duplexes with the complimentary RNA, The ODNs containing the modified nucleosides were significantly resistant to nucleolytic hydrolysis by both snake venom phosphodiesterase (a 3'-exonuclease) and DNase 1 (an endonuclease) and were also very stable in PBS containing 50% human serum. It is worthwhile to note that these ODNs contain natural phosphodiester linkages. Furthermore, the duplexes formed by the ODNs containing the modified nucleosides and their complementary RNAs were good substrates for Escherichia coli RNase H and HeLa cell nuclear extracts as a source of human RNase H. Thus. these ODNs were identified as candidates for antisense molecules.