3'-O-(4,4'-dimethoxytrityl)-α-thymidine | 134031-87-1

• 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: 3'-O-(4,4'-dimethoxytrityl)-α-thymidine
• 英文别名: 1-[(2S,4S,5R)-4-[bis(4-methoxyphenyl)-phenylmethoxy]-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 134031-87-1
• 化学式: C₃₁H₃₂N₂O₇
• 分子量: 544.604
• InChiKey: UDDSFNVDTHTTMK-IARZGTGTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  40
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  双(二异丙基氨基)(2-氰基乙氧基)膦 、 3'-O-(4,4'-dimethoxytrityl)-α-thymidine 在 二异丙基铵盐四氮唑 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 Diisopropyl-phosphoramidous acid (2R,3S,5S)-3-[bis-(4-methoxy-phenyl)-phenyl-methoxy]-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethyl ester 2-cyano-ethyl ester
  参考文献：
  名称：

  Synthesis and Physicochemical Properties of Alternating .alpha.,.beta.-Oligodeoxyribonucleotides with Alternating (3'.fwdarw.3')- and (5'.fwdarw.5')-Internucleotidic Phosphodiester Linkages

  摘要：

  A simple and straightforward synthesis of alpha-2'-deoxycytidine and alpha-2'-deoxyadenosine derivatives 6a,b has been achieved from commercial N-4-benzoyl-beta-2'-deoxycytidine and N-6-benzoyl-beta-2'-deoxyadenosine, respectively. Properly protected alpha-2'-deoxyribonucleosides 8a-d were converted to the corresponding 5'-phosphoramidite derivatives 9a-d. These and commercial beta-2'-deoxyribonucleoside 3'-phosphoramidites were readily incorporated into alternating alpha,beta-oligodeoxyribonucleotides with alternating (3'-->3')- and (5'-->5')-internucleotidic phosphodiester linkages by standard solid-phase synthesis methods. The alpha,beta-oligodeoxyribonucleotide 12 (Scheme 3) was considerably more resistant to hydrolysis catalyzed by snake venom phosphodiesterase, calf spleen phosphodiesterase, and S1 nuclease than the parent unmodified oligonucleotide 17 (Table 2). Thermal stability of the complex composed of 12 and complementary unmodified beta-oligomer 18 was comparable to that measured for the hybrid composed of the beta-oligodeoxyribonucleoside phosphorothioate 20 and 18 but less than that of the native DNA duplex 17:18 (Table 3). The differences in thermal stability (Delta T-m) and free energy of dissociation (Delta Delta G(37)degrees) observed between the duplex 12:18 and the singly mismatched complex 12:19 (9 degrees C and -2.5 kcal/mol, respectively) (Tables 3 and 4) suggest that the sequence specificity;of 12 toward a complementary unmodified beta-DNA oligomer is comparable to that of 17. In addition, the CD spectrum of 12:18 at 22 degrees C resembles more closely that of the natural DNA duplex 17:18 than that of the alpha,beta-DNA duplex 12:13 (Figure 3). These findings indicate that the duplex 12:18 exhibits, at least to some extent, a B-type helicity. The alpha,beta-oligodeoxyribonucleotide 12 formed also a complex with the complementary beta-oligoribonucleotide 23 but with much reduced affinity (T-m = 35 degrees C) than that measured with the complementary DNA sequence 18 (T-m = 54 degrees C). CD spectroscopy indicated that the complex 12:23 adopted a conformation similar to that observed for duplex 17:23 at 22 degrees C. Unlike the DNA-RNA heteroduplex 17:23, the complex 12:23 was not a substrate for E. coli RNase H.

  DOI：

  10.1021/jo00111a009
• 作为产物：
  描述：

  5'-O-acetyl-3'-O-(4,4'-dimethoxytrityl)-α-thymidine 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以95%的产率得到3'-O-(4,4'-dimethoxytrityl)-α-thymidine
  参考文献：
  名称：

  Targeting Chimeric alpha,beta-Oligonucleotides to the Flanks of a Stem in DNA. The Enhanced Effect of an Intercalator.

  摘要：

  3'-O-(4,4'-Dimethoxytrityl)-5-methyl-N-4-(1-pyrenylmethyl)-alpha-cytidine (7) was prepared from alpha-thymidine by the reaction of 1-pyrenylmethylamine with an appropriate protected 4-(1,2,4-triazolyl)-alpha-thymidine derivative 5. 3'-O-(4,4'-Dimethoxytrityl-alpha-thymidine (9) was synthesized by successive, 5'-O-acetylation, 3'-O-tritylation and 5'-O-deacetylation of alpha-thymidine. Phosphitylation of the 5'-hydroxy group of 7 and 9 afforded the amidites 8 and 10. These amidites and commercial beta-2'-deoxyribonucleoside-3'-phosphoramidites were used in the synthesis of chimeric ODNs with 3'-3' and 5'-5' internucleotidic phosphodiester linkages. The stability of a DNA three way junction (TWJ) was studied by observing the thermal melting when a DNA was targeted to the flanks of a hairpin. The TWJ was considerably stabilized when 7 and 9 were inserted into the junction region. The corresponding duplex obtained by deleting the hairpin, however, was destabilized on insertion of 7 and 9.

  DOI：

  10.3891/acta.chem.scand.51-1245

文献信息

• 5'-END DERIVATIVES
  申请人：Manoharan Muthiah

  公开号：US20130323836A1

  公开（公告）日：2013-12-05

  The present invention provides compounds of formula (1). Another aspect of the invention relates to a method of inhibiting the expression of a gene in call, the method comprising (a) contacting an oligonucleotide of the invention with the cell; and (b) maintaining the cell from step (a) for a time sufficient to obtain degradation of the mRNA of the target gene.

  本发明提供了式（1）的化合物。发明的另一个方面涉及抑制细胞中基因表达的方法，该方法包括（a）将本发明的寡核苷酸与细胞接触；以及（b）维持从步骤（a）中的细胞足够时间以获得目标基因mRNA的降解。
• Synthesis and Physicochemical Properties of Alternating .alpha.,.beta.-Oligodeoxyribonucleotides with Alternating (3'.fwdarw.3')- and (5'.fwdarw.5')-Internucleotidic Phosphodiester Linkages
  作者：Masakazu Koga、Andrzej Wilk、Michael F. Moore、Carlo L. Scremin、Liang Zhou、Serge L. Beaucage

  DOI：10.1021/jo00111a009

  日期：1995.3

  A simple and straightforward synthesis of alpha-2'-deoxycytidine and alpha-2'-deoxyadenosine derivatives 6a,b has been achieved from commercial N-4-benzoyl-beta-2'-deoxycytidine and N-6-benzoyl-beta-2'-deoxyadenosine, respectively. Properly protected alpha-2'-deoxyribonucleosides 8a-d were converted to the corresponding 5'-phosphoramidite derivatives 9a-d. These and commercial beta-2'-deoxyribonucleoside 3'-phosphoramidites were readily incorporated into alternating alpha,beta-oligodeoxyribonucleotides with alternating (3'-->3')- and (5'-->5')-internucleotidic phosphodiester linkages by standard solid-phase synthesis methods. The alpha,beta-oligodeoxyribonucleotide 12 (Scheme 3) was considerably more resistant to hydrolysis catalyzed by snake venom phosphodiesterase, calf spleen phosphodiesterase, and S1 nuclease than the parent unmodified oligonucleotide 17 (Table 2). Thermal stability of the complex composed of 12 and complementary unmodified beta-oligomer 18 was comparable to that measured for the hybrid composed of the beta-oligodeoxyribonucleoside phosphorothioate 20 and 18 but less than that of the native DNA duplex 17:18 (Table 3). The differences in thermal stability (Delta T-m) and free energy of dissociation (Delta Delta G(37)degrees) observed between the duplex 12:18 and the singly mismatched complex 12:19 (9 degrees C and -2.5 kcal/mol, respectively) (Tables 3 and 4) suggest that the sequence specificity;of 12 toward a complementary unmodified beta-DNA oligomer is comparable to that of 17. In addition, the CD spectrum of 12:18 at 22 degrees C resembles more closely that of the natural DNA duplex 17:18 than that of the alpha,beta-DNA duplex 12:13 (Figure 3). These findings indicate that the duplex 12:18 exhibits, at least to some extent, a B-type helicity. The alpha,beta-oligodeoxyribonucleotide 12 formed also a complex with the complementary beta-oligoribonucleotide 23 but with much reduced affinity (T-m = 35 degrees C) than that measured with the complementary DNA sequence 18 (T-m = 54 degrees C). CD spectroscopy indicated that the complex 12:23 adopted a conformation similar to that observed for duplex 17:23 at 22 degrees C. Unlike the DNA-RNA heteroduplex 17:23, the complex 12:23 was not a substrate for E. coli RNase H.
• Targeting Chimeric alpha,beta-Oligonucleotides to the Flanks of a Stem in DNA. The Enhanced Effect of an Intercalator.
  作者：Ahmed F. Khattab、Erik B. Pedersen、Hans Vallberg

  DOI：10.3891/acta.chem.scand.51-1245

  日期：——

  3'-O-(4,4'-Dimethoxytrityl)-5-methyl-N-4-(1-pyrenylmethyl)-alpha-cytidine (7) was prepared from alpha-thymidine by the reaction of 1-pyrenylmethylamine with an appropriate protected 4-(1,2,4-triazolyl)-alpha-thymidine derivative 5. 3'-O-(4,4'-Dimethoxytrityl-alpha-thymidine (9) was synthesized by successive, 5'-O-acetylation, 3'-O-tritylation and 5'-O-deacetylation of alpha-thymidine. Phosphitylation of the 5'-hydroxy group of 7 and 9 afforded the amidites 8 and 10. These amidites and commercial beta-2'-deoxyribonucleoside-3'-phosphoramidites were used in the synthesis of chimeric ODNs with 3'-3' and 5'-5' internucleotidic phosphodiester linkages. The stability of a DNA three way junction (TWJ) was studied by observing the thermal melting when a DNA was targeted to the flanks of a hairpin. The TWJ was considerably stabilized when 7 and 9 were inserted into the junction region. The corresponding duplex obtained by deleting the hairpin, however, was destabilized on insertion of 7 and 9.