5'-O-(2-(2-fluoro-6-nitrophenyl)ethoxycarbonyl)thymidine | 179691-38-4

• 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: 5'-O-(2-(2-fluoro-6-nitrophenyl)ethoxycarbonyl)thymidine
• 英文别名: 2-(2-fluoro-6-nitrophenyl)ethyl [(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl carbonate
• CAS: 179691-38-4
• 化学式: C₁₉H₂₀FN₃O₉
• 分子量: 453.381
• InChiKey: WGVSLTSUPYYBDX-ARFHVFGLSA-N

物化性质

• 密度：
  1.484±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  160
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2-(2-fluoro-6-nitrophenyl)ethan-1-ol 在 吡啶 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 7.5h， 生成 5'-O-(2-(2-fluoro-6-nitrophenyl)ethoxycarbonyl)thymidine
  参考文献：
  名称：

  Photolabile protecting groups for nucleosides: Synthesis and photodeprotection rates

  摘要：

  o-Nitrobenzyloxycarbonyl and a number of related groups have been tested for the photolabile protection of nucleoside 5'-hydroxyls. The rates of photodeprotection were found to vary by approximately 17 fold in a series of 5'-O-protected thymidine derivatives irradiated at 365 nm under identical conditions. The homologous 2-(o-nitrophenyl)ethoxycarbonyl group and its derivatives were found to be removed approximately 2-fold faster than the corresponding o-nitrobenzyloxycarbonyl group, possibly due to an increased rare of alpha-hydrogen abstraction by the photo-excited nitro group. Photolysis rates were affected by substitutions on both the phenyl ring and alpha-carbon, with the strongest rate enhancements caused by the presence of a methyl or second o-nitrophenyl group in the alpha-position. Among the ring-substituted derivatives studied, o-nitro and o-iodo had the strongest enhancement effects on photodeprotection, while an o-fluoro group reduced the rate of photodeprotection. In general, substitutions at other positions on the phenyl ring had less effect on photolysis rates. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4020(97)00154-3

文献信息

• [DE] NUCLEOSID-DERIVATE MIT PHOTOLABILEN SCHUTZGRUPPEN<br/>[EN] NUCLEOSIDE DERIVATIVES WITH PHOTOLABILE PROTECTIVE GROUPS<br/>[FR] DERIVES DE NUCLEOSIDES COMPORTANT DES GROUPES PROTECTEURS PHOTOLABILES
  申请人：PFLEIDERER, Wolfgang

  公开号：WO1996018634A2

  公开（公告）日：1996-06-20

  (DE) Die Erfindung betrifft Nucleosid-Derivate mit photolabilen Schutzgruppen der allgemeinen Formel (I) in der R1 = H, NO2, CN, OCH3, Halogen oder Alkyl oder Alkoxyalkyl mit 1 bis 4 C-Atomen; R2 = H, OCH3; R3 = H, F, Cl, Br, NO2; R4 = H, Halogen, OCH3 oder ein Alkylrest mit 1 bis 4 C-Atomen; R5 = H oder eine übliche funktionelle Schutzgruppe für das Sauerstoffatom, die sich für die Herstellung von Oligonucleotiden eignet; R6 = H, OH, Halogen oder XR8, wobei X = O oder S und R8 eine in der Nucleotidchemie übliche Schutzgruppe darstellt; B = Adenin, Cytosin, Guanin, Thymin, Uracil, 2,6-Diaminopurin-9-yl, Hypoxanthin-9-yl, 5-Methylcytosin-1-yl, 5-Amino-4-imidazolcarbonsäureamid-1-yl oder 5-Amino-4-imidazolcarbonsäureamid-3-yl, wobei im Falle von B = Adenin, Cytosin oder Guanin die primäre Aminofunktion ggf. eine permanente Schutzgruppe aufweist. Diese Derivate können für die lichtgesteuerte Synthese von Oligonucleotiden auf einem DNA-Chip verwendet werden.(EN) The invention concerns nucleoside derivatives with photolabile protective groups of general formula (I), in which R1 is H, NO2, CN, OCH3, halogen or alkyl or alkoxyalkyl with 1 to 4 carbon atoms; R2 is H, OCH3; R3 is H, F, Cl, Br, NO2; R4 is H, halogen, OCH3 or an alkyl group with 1 to 4 carbon atoms; R5 is H or a conventional functional protective group for the oxygen atom, which group is suitable for preparing oligonucleotides; R6 is H, OH, halogen or XR8, wherein X is O or S and R8 is a protective group conventional in nucleotide chemistry; B is adenine, cytosine, guanine, thymine, uracil, 2,6-diaminopurine-9-yl, hypoxanthine-9-yl, 5-methylcytosine-1-yl, 5-amino-4-imidazole carboxylic acid amide-1-yl or 5-amino-4-imidazole carboxylic acid amide-3-yl, wherein, if B is adenine, cytosine or guanine, the primary amino function optionally comprises a permanent protective group. These derivatives can be used for the light-controlled synthesis of oligonucleotides on a DNA chip.(FR) La présente invention concerne des dérivés de nucléosides comportant des groupes protecteurs photolabiles, de formule générale (I) où R1 = H, NO2, CN, OCH3, halogène ou alcoyle ou alcoxyalcoyle ayant de 1 à 4 atomes de C; R2 = H, OCH3; R3 = H, F, Cl, Br, NO2; R4 = H, halogène, OCH3 ou un reste d'alcoyle ayant de 1 à 4 atomes de C; R5 = H ou un groupe protecteur fonctionnel usuel pour l'atome d'oxygène, convenant pour la préparation d'oligonucléotides; R6 = H, OH, halogène ou XR8, avec X = 0 ou S et R8 étant un groupe protecteur usuel en chimie des nucléotides; B = adénine, cytosine, guanine, thymine, uracile, 2, 6-diaminopurin-9-yle, hypoxanthin-9-yle, 5-méthylcytosin-1-yle, 5-amino-4-amide d'acide carboxylique imidazol-1-yle ou 5-amino-4-amide d'acide carboxylique imidazol-3-yle. Dans le cas où B = adénine, cytosine ou guanine, la fonction amino primaire comporte, le cas échéant, un groupe protecteur permanent. Ces dérivés peuvent être employés pour la synthèse, commandée par la lumière, d'oligonucléotides sur une plaquette d'ADN.

  这项发明涉及一般公式（I）的核苷酸衍生物，其中： R1 = H、NO2、CN、OCH3、卤素或直链或醚链（直链或醚链含有1至4个碳原子）的根基； R2 = H、OCH3； R3 = H、F、Cl、Br、NO2； R4 = H、卤素、OCH3或直链（含有1至4个碳原子的根基）； R5 = H或氧的常规功能守护基团（可适合制备核苷酸的生产）； R6 = H、OH、卤素或XR8，其中X = O或S，而R8是核苷酸化学中常规的保护基团； B = 精氨酸、鸟嘌呤、胞嘧啶、胸腺嘧啶、尿嘧啶、2,6-二胺嘌呤-9-yl、嘌呤呤呤-9-yl、5-甲基鸟嘌呤-1-yl、5-氨基-4-甲酰胺-1-yl或5-氨基-4-甲酰胺-3-yl；当B是精氨酸、鸟嘌呤或胞嘧啶时，主要氨基功能可选性地 consisted by a permanent protective group。这些衍生物可用于光控合成核苷酸 oligine 在 DNA 芯上的用途。
• Photolabile protecting groups for nucleosides: Synthesis and photodeprotection rates
  作者：Ahmad Hasan、Klaus-Peter Stengele、Heiner Giegrich、Paul Cornwell、Kenneth R. Isham、Richard A. Sachleben、Wolfgang Pfleiderer、Robert S. Foote

  DOI：10.1016/s0040-4020(97)00154-3

  日期：1997.3

  o-Nitrobenzyloxycarbonyl and a number of related groups have been tested for the photolabile protection of nucleoside 5'-hydroxyls. The rates of photodeprotection were found to vary by approximately 17 fold in a series of 5'-O-protected thymidine derivatives irradiated at 365 nm under identical conditions. The homologous 2-(o-nitrophenyl)ethoxycarbonyl group and its derivatives were found to be removed approximately 2-fold faster than the corresponding o-nitrobenzyloxycarbonyl group, possibly due to an increased rare of alpha-hydrogen abstraction by the photo-excited nitro group. Photolysis rates were affected by substitutions on both the phenyl ring and alpha-carbon, with the strongest rate enhancements caused by the presence of a methyl or second o-nitrophenyl group in the alpha-position. Among the ring-substituted derivatives studied, o-nitro and o-iodo had the strongest enhancement effects on photodeprotection, while an o-fluoro group reduced the rate of photodeprotection. In general, substitutions at other positions on the phenyl ring had less effect on photolysis rates. (C) 1997 Elsevier Science Ltd.
• NUCLEOSID-DERIVATE MIT PHOTOLABILEN SCHUTZGRUPPEN
  申请人：Pfleiderer, Wolfgang

  公开号：EP0797580A2

  公开（公告）日：1997-10-01
• US5763599A
  申请人：——

  公开号：US5763599A

  公开（公告）日：1998-06-09
• New Photolabile Protecting Groups in Nucleoside and Nucleotide Chemistry—Synthesis, Cleavage Mechanisms and Applications
  作者：H. Giegrich、S. Eisele-Bühler、Chr Hermann、E. Kvasyuk、R. Charubala、W. Pfleiderer

  DOI：10.1080/07328319808004738

  日期：1998.9

  New photolabile protecting groups have been found in the 2-(2-nitrophenyl)ethoxycarbonyl and the 2-(2-nitrophenyl)ethylsulfonyl group, respectively. The influence of substituents at the phenyl ring as well as the side-chain has been investigated regarding the photolysis rates on irradiation at 365 mn. beta-Branching in the side-chain leads to highly increased rates of photodeprotection. A new type of photocleavage mechanism consisting of a photoinduced beta-elimination process is proposed.