1-(α-D-arabinofuranosyl)-5-methyl-2,4(1H,3H)-pyrimidinedione | 4348-74-7

• 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: 1-(α-D-arabinofuranosyl)-5-methyl-2,4(1H,3H)-pyrimidinedione
• 英文别名: 1-(α-D-Arabinofuranosyl)-5-methyluracil；1-(α-D-arabinofuranosyl)thymine；1-α-D-arabinofuranosyl-5-methyl-1H-pyrimidine-2,4-dione；1-α-D-Arabinofuranosyl-thymin；1-alpha-D-Arabinofuranosylthymine；1-[(2S,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 4348-74-7
• 化学式: C₁₀H₁₄N₂O₆
• 分子量: 258.231
• InChiKey: DWRXFEITVBNRMK-JAKMQLQISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  119
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(α-D-arabinofuranosyl)-5-methyl-2,4(1H,3H)-pyrimidinedione 在 吡啶 、 4-二甲氨基吡啶 、 四丁基氟化铵 、 溶剂黄146 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 76.0h， 生成 N4-[2-(4-nitrophenyl)ethoxycarbonyl]-1-{5-O-(4-monomethoxytrityl)-2-O-[2-(4-nitrophenyl)ethoxycarbonyl]-α-D-arabinofuranosyl}cytosine
  参考文献：
  名称：

  Nucleotides. LXXIV Synthesis of a-D-Arabino-oligonucleotides

  摘要：

  The 5 alpha-D-arabinofuranosylnucleosides alpha-araU (15), alpha-araT (18), alpha-araC (22), alpha-araA (25), and alpha-araG (28) have been synthesized by the modified silyl-method. The amino groups at the nucleobases and the 2'-hydroxy group at the sugar moiety were protected by the 2-(4-nitro-phenyl) ethoxycarbonyl (npeoc) group (37-40) and the amide function in alpha-araG was additionally blocked by the 2-(4-nitrophenyl)ethyl group (63) to improve solubility in organic solvents. Mono-and dimethoxytritylation of the 5'-OH group was performed in the usual manner to give 41-48, 64, and 65 in high yields and further substitution of the 3'-OH group led to the monomeric building blocks 66-75 as well as the 3'-O-succinoyl derivatives 76-85 functioning as starting units in solid-support oligonucleotide synthesis. A large number of oligo-alpha-arabinonucleotides have been prepared on modified CPG-material applying the npeoc/npe strategy as a very efficient synthetic tool for highly purified, homogenous oligomers. Hybridizations between alpha-arabinonucleotide strands revealed in analogy to earlier findings an antiparallel orientation whereas the combination of an oligo-alpha-D-arabinonucleotide with a complementary oligo-2'-deoxy-beta-D-ribofuranosylnucleotide showed base-pairing only if a parallel polarity was present. The advantages in oligo-alpha-arabinonucleotide synthesis were furthermore demonstrated by the synthesis of the t alpha-ANA(his) a structural analog of the natural tRNA(his) of the phage T5.

  DOI：

  10.1080/15257770500267113
• 作为产物：
  描述：

  O,O-二(三甲基甲硅烷基)胸苷 在 trimethylsilyl trifluorosulfonate 、 sodium methylate 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 0.75h， 生成 1-(α-D-arabinofuranosyl)-5-methyl-2,4(1H,3H)-pyrimidinedione
  参考文献：
  名称：

  Nucleotides. LXXIV Synthesis of a-D-Arabino-oligonucleotides

  摘要：

  The 5 alpha-D-arabinofuranosylnucleosides alpha-araU (15), alpha-araT (18), alpha-araC (22), alpha-araA (25), and alpha-araG (28) have been synthesized by the modified silyl-method. The amino groups at the nucleobases and the 2'-hydroxy group at the sugar moiety were protected by the 2-(4-nitro-phenyl) ethoxycarbonyl (npeoc) group (37-40) and the amide function in alpha-araG was additionally blocked by the 2-(4-nitrophenyl)ethyl group (63) to improve solubility in organic solvents. Mono-and dimethoxytritylation of the 5'-OH group was performed in the usual manner to give 41-48, 64, and 65 in high yields and further substitution of the 3'-OH group led to the monomeric building blocks 66-75 as well as the 3'-O-succinoyl derivatives 76-85 functioning as starting units in solid-support oligonucleotide synthesis. A large number of oligo-alpha-arabinonucleotides have been prepared on modified CPG-material applying the npeoc/npe strategy as a very efficient synthetic tool for highly purified, homogenous oligomers. Hybridizations between alpha-arabinonucleotide strands revealed in analogy to earlier findings an antiparallel orientation whereas the combination of an oligo-alpha-D-arabinonucleotide with a complementary oligo-2'-deoxy-beta-D-ribofuranosylnucleotide showed base-pairing only if a parallel polarity was present. The advantages in oligo-alpha-arabinonucleotide synthesis were furthermore demonstrated by the synthesis of the t alpha-ANA(his) a structural analog of the natural tRNA(his) of the phage T5.

  DOI：

  10.1080/15257770500267113

文献信息

• A Surprising Ring Opening Mechanism in the Formation of α-D-Arabinofuranosyl Nucleosides from 5-Substituted Uracils
  作者：Per Trolle Jørgensen、Erik B. Pedersen、Claus Nielsen

  DOI：10.1055/s-1992-26363

  日期：——

  Reaction of silylated 5-substituted uracil derivatives 6 with methyl 2,3,5-tri-O-benzoyl-α-D-arabinofuranoside (3) in the presence of trimethylsilyl trifluoromethanesulfonate afforded a mixture of the corresponding 5-substituted 1-(2,3,5-tri-O-benzoyl-α-D-arabinofuranosyl)uracils 7 and the acyclo 2,3,5-tri-O-benzoyl-1-O-methyl-1-(uracil-1-yl)-D-arabinitols 9 with the methoxy group intact at C-1. Compound 7 was deprotected with methanolic ammonia to give 8. Compound 7 was also reacted with Lawesson's Reagent to generate the corresponding 4-thio-α-D-arabinofuranoside nucleoside 14 which was deprotected by treatment with methanolic ammonia to give the nucleosides 15. Deprotected acyclo nucleosides 10 were likewise obtained from compounds 9. The mechanism for formation of the nucleosides 7 is discussed and the acyclo nucleosides 9 are believed to be intermediates.

  在三甲基硅基三氟甲磺酸酯的存在下，硅烷化的5-取代尿嘧啶衍生物6与甲基2,3,5-三-O-苯甲酰基-α-D-阿拉伯呋喃糖苷（3）反应，生成相应的5-取代1-(2,3,5-三-O-苯甲酰基-α-D-阿拉伯呋喃糖基)尿嘧啶7和非环状的2,3,5-三-O-苯甲酰基-1-O-甲基-1-(尿嘧啶-1-基)-D-阿拉伯醇9的混合物，其中C-1位的甲氧基保持完整。化合物7通过与甲醇氨反应去保护，得到8。化合物7还与Lawesson试剂反应，生成相应的4-硫-α-D-阿拉伯呋喃糖核苷14，后者通过甲醇氨处理去保护，得到核苷15。从化合物9也得到了去保护的非环状核苷10。讨论了核苷7的形成机理，并且认为非环状核苷9是中间体。
• Oligo (.alpha.-arabinofuranosyl nucleotides) and
  申请人：Microprobe Corporation

  公开号：US05177196A1

  公开（公告）日：1993-01-05

  Novel oligonucleotides formed from .alpha.-D-arabinofuranosyl nucleoside monomers, including oligonucleotides in which one or more of the monomer units is functionalized, are disclosed herein, as well as functionalized monomeric .alpha.-D-arabinofuranosyl nucleosides and nucleotides. A generic formula for the oligomers is: ##STR1## in which B is a nucleotide base which will vary from one monomeric unit to the next in a preselected oligonucleotide sequence; R is phosphate, phsophorothioate, phosphoramidate, or alkanephosphonate; t is 1 for functionalized monomeric units and zero for the others; W is a chemical linker arm; A is a functional group; and n is the number of monomeric units in the oligomer. The oligomers are useful for diagnostic and chemotherapeutic uses. A novel reaction is also disclosed, in which an .alpha.-D-arabinofuranosyl nucleoside with exposed hydroxyls at the 2'- and 3'-positions is selectively protected at the 2'-position in a single reaction.

  本文披露了由α-D-阿拉伯糖核苷单体形成的新型寡核苷酸，包括其中一个或多个单体单元被功能化的寡核苷酸，以及功能化单体α-D-阿拉伯糖核苷和核苷酸。 寡聚物的通用公式为：##STR1## 其中B是核苷酸碱基，将在预选的寡核苷酸序列中从一个单体单元到下一个单体单元变化; R是磷酸盐，磷硫酸盐，磷酰胺酯或脂肪族磷酸酯; t为1用于功能化单体单元，其他单体单元为零; W是化学连接臂; A是功能基团; n是寡聚物中单体单元的数量。 这些寡聚体可用于诊断和化疗用途。 还披露了一种新的反应，在该反应中，具有2'-和3'-位暴露羟基的α-D-阿拉伯糖核苷在单个反应中在2'-位置被选择性地保护。
• Mutagenic nucleoside analogs for the treatment of viral disease
  申请人：Koronis Pharmaceuticals, Inc.

  公开号：US20030170872A1

  公开（公告）日：2003-09-11

  The present invention relates to methods of treating viral disease using mutagenic nucleoside analogs.

  本发明涉及使用诱变核苷类似物治疗病毒性疾病的方法。
• [EN] METHODS AND COMPOSITIONS FOR SEQUENCE-SPECIFIC HYBRIDIZATION OF RNA BY 2'-5' OLIGONUCLEOTIDES<br/>[FR] PROCEDES ET COMPOSITIONS POUR L'HYBRIDATION SPECIFIQUE DE SEQUENCE D'ARN PAR DES 2'-5' OLIGONUCLEOTIDES
  申请人：DYAD PHARMACEUTICAL CORPORATION

  公开号：WO1998000564A1

  公开（公告）日：1998-01-08

  (EN) A 2'-5' oligonucleotide is hybridized to complementary nucleic acid which may be RNA or duplex DNA. The 2'-5' oligonucleotide is a methylphosphonate, a phosphorothioate or, especially preferred, a phosphodiester.(FR) Un 2'-5' oligonucléotide est hybridé avec un acide nucléique complémentaire pouvant être un ARN ou un ADN duplex. Ce 2'-5' oligonucléotide est un méthylphosphonate, un phosphorothioate ou bien, idéalement, un phosphodiester.

  一个2'-5' 聚二脱氧核苷酸与互补核酸（可能是RNA或双链DNA）杂交。2'-5' 聚二脱氧核苷酸是一种甲基磷酸二酯、磷酸硫醚或，最好，是磷酸二酯。
• Efficient and Selective Enzymatic Acylation Reaction: Separation of Furanosyl and Pyranosyl Nucleosides
  作者：Jyotirmoy Maity、Gaurav Shakya、Sunil K. Singh、Vasulinga T. Ravikumar、Virinder S. Parmar、Ashok K. Prasad

  DOI：10.1021/jo800731u

  日期：2008.7.1

  Candida antarctica lipase-B (CAL-B) immobilized on lewatite selectively acylated the primary hydroxyl group of the furanosyl nucleoside in a mixture of 1-(alpha-D-arabinofuranosyl)thymine and 1-(alpha-D-arabinopyranosyl)thymine. This selective biocatalytic acylation of furanosyl nucleoside has enabled us an easy separation of arabinofuranosyl thymine from an inseparable mixture with arabinopyranosyl thymine. The primary hydroxyl selective acylation methodology of arabinonucleoside has also been successfully used for the separation of 1-(beta-D-xylofuranosyl)thymine and 1-(beta-D-xylopyranosyl)thymine from a mixture of the two, which demonstrate the generality of the enzymatic methodology for separation of furanosyl and pyranosyl nucleosides.