N-{9-[(2R,4S,5S)-5-({[bis(4-methoxyphenyl)(phenyl)methyl]sulfanyl}methyl)-4-hydroxyoxolan-2-yl]-9H-purin-6-yl}benzamide | 184229-73-0

• 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: N-{9-[(2R,4S,5S)-5-({[bis(4-methoxyphenyl)(phenyl)methyl]sulfanyl}methyl)-4-hydroxyoxolan-2-yl]-9H-purin-6-yl}benzamide
• 英文别名: N-[9-[(2R,4S,5S)-5-[[bis(4-methoxyphenyl)-phenylmethyl]sulfanylmethyl]-4-hydroxyoxolan-2-yl]purin-6-yl]benzamide
• CAS: 184229-73-0
• 化学式: C₃₈H₃₅N₅O₅S
• 分子量: 673.792
• InChiKey: CZSMCGMEUCGKIT-WIHCDAFUSA-N

物化性质

• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  49
• 可旋转键数：
  11
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  146
• 氢给体数：
  2
• 氢受体数：
  9

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 、 N-{9-[(2R,4S,5S)-5-({[bis(4-methoxyphenyl)(phenyl)methyl]sulfanyl}methyl)-4-hydroxyoxolan-2-yl]-9H-purin-6-yl}benzamide 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 1.0h， 以72%的产率得到N-{9-[(2R,4S,5S)-5-({[bis(4-methoxyphenyl)(phenyl)methyl]sulfanyl}methyl)-4-({[bis(propan-2-yl)amino](2-cyanoethoxy)phosphanyl}oxy)oxolan-2-yl]-9H-purin-6-yl}benzamide
  参考文献：
  名称：

  DNA阵列的新概念

  摘要：

  摘要我们将在寡聚脱氧核苷酸中插入一个切割位点，可用于选择性和定量切割。因此，我们合成了四个5'-S-（4,4'-二甲氧基三苯甲基）-巯基-2'-脱氧核苷酸-3'-O-（2-氰基乙氧基二异丙基氨基）-亚磷酸酯（5a–d）。描述了PS和CS键的裂解（Mag，M .;Lücking，S .; Engels，JW合成和选择性裂解含有桥连的核苷酸间5'-硫代磷酸酯键的低聚脱氧核苷酸Nucleic Acids Res。1991，19（7 ），1437–1441;万豪酒店，JH; Mottahedeh，M .;里斯（Reese），CB 9-（4-甲氧基苯基）氧杂蒽-9-硫醇：一种有用的硫醇试剂。Tetrahedron Lett。1990，31（51）， 7485–7488； Divakar，KJ； Mottoh，A。； Reese，CB； Shanghvi，YS合成嘧啶核糖苷2'硫代类似物的方法。珀金（

  DOI：

  10.1081/ncn-120023015
• 作为产物：
  描述：

  2'-脱氧腺苷 在 吡啶 、 sodium hydroxide 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 吡啶 、 乙醇 为溶剂， 反应 14.12h， 生成 N-{9-[(2R,4S,5S)-5-({[bis(4-methoxyphenyl)(phenyl)methyl]sulfanyl}methyl)-4-hydroxyoxolan-2-yl]-9H-purin-6-yl}benzamide
  参考文献：
  名称：

  Alteration of DNA Primary Structure by DNA Topoisomerase I. Isolation of the Covalent Topoisomerase I−DNA Binary Complex in Enzymatically Competent Form

  摘要：

  DNA ligation by DNA topoisomerase I was investigated employing synthetic DNA substrates containing a single strand nick. Site-specific cleavage of the DNA by topoisomerase I in proximity to the nick resulted in uncoupling of the cleavage and ligation reactions of the enzyme, thereby trapping the covalent enzyme-DNA intermediate. DNA cleavage could be reversed by the addition of acceptor oligonucleotides containing a free 5'-OH group and capable of hybridizing to the noncleaved strand of the ''suicide substrates''. Utilizing accepters with partial complementarity, modification of nucleic acid structure has been obtained. Modifications included the formation of DNA insertions, deletions, and mismatches. To further evaluate the potential of topoisomerase I to mediate structural transformations of DNA, acceptor oligonucleotides containing nucleophiles other than OH groups at the 5'-end were studied as substrates for the topoisomerase I-mediated ligation reaction. Toward this end, oligonucleotides containing 5'-thio, amino, and hydroxymethylene moieties were synthesized. Initial investigations utilizing a coupled cleavage-ligation assay suggested that only the modified acceptor containing an additional methylene group underwent efficient enzyme-mediated ligation. However, as linear DNA is not a preferred substrate for topoisomerase I, the enzyme-DNA intermediate was purified to homogeneity, thereby allowing investigation of the ligation reaction independent of the forward reaction that formed the covalent binary complex. The isolated complex consisted of equimolar enzyme and DNA, with topoisomerase I covalently bound to a specific site on the DNA duplex in an enzymatically competent form. Displacement of the enzyme-linked tyrosine moiety of the enzyme-DNA binary complex was effected by all the modified acceptor oligonucleotides, affording unnatural internucleosidic linkages at a specific site. Characterization of the formed linkages was effected both by enzymatic and chemical degradation studies. Comparative analysis revealed overall differences in the efficiency and rate of the topoisomerase I-mediated ligation of the modified acceptors. Moreover, the facility of ligation of the amino acceptor was significantly enhanced at increasing pH values. In addition, the method utilized to obtain the topoisomerase I-DNA intermediate is capable of affording large quantities required for further mechanistic and physicochemical characterization of the formed binary complex.

  DOI：

  10.1021/ja961788h

文献信息

• Efficient Solid Phase Synthesis of Cleavable Oligodeoxynucleotides Based on a Novel Strategy for the Synthesis of 5?-S-(4,4?-Dimethoxytrityl)-2?-deoxy-5?-thionucleoside Phosphoramidites
  作者：Kerstin Jahn-Hofmann、Joachim?W. Engels

  DOI：10.1002/hlca.200490252

  日期：2004.11

  cleavage site into an oligodeoxynucleotide can be achieved by utilizing the four 5′-S-(4,4′-dimethoxytrityl)-2′-deoxy-5′-thionucleoside 3′-(2-cyanoethyl diisopropylphosphoramidites) 5 and 15a–c (Fig. 1). Based on the silver ion assisted cleavage of PS and CS bonds, we synthesized oligodeoxynucleotides with an achiral 5′-phosphorothioate linkage 3′–O–P–S–5′ by the solid-phase phosphoramidite procedure

  通过使用四个5'- S-（4,4'-二甲氧基三苯甲基）-2'-脱氧-5'-硫代核苷3'-（2-氰基乙基二异丙基亚磷酰胺基）5可以实现将特定切割位点掺入寡脱氧核苷酸中和15a – c（图1）。基于银离子对PS和CS键的裂解，我们通过固相亚磷酰胺合成了具有非手性5'-硫代磷酸酯键3'–O–P–S–5'的寡脱氧核苷酸。这些修饰的寡脱氧核苷酸的有效裂解可通过HPLC，PAGE和表面等离振子共振（SPR）光谱进行检测。释放的5'-硫醇部分可直接用于带有适当功能化的报告基团的反应后标记。
• OLIGONUCLEOTIDE SYNTHESIS
  申请人：ROCHE INNOVATION CENTER COPENHAGEN A/S

  公开号：US20210309690A1

  公开（公告）日：2021-10-07

  The invention relates to a process for the manufacture of an oligonucleotide comprising at least one non-chiral phosphorothioate intemucleoside linkage of formula (I) wherein R 1 is as defined in the description and in the claims.