O^2'_,O3'-cyclohexane-1,1-diyl-4'-hydroxymethyl-uridine | 63592-89-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: O^2'_,O3'-cyclohexane-1,1-diyl-4'-hydroxymethyl-uridine
• 英文别名: 2',3'-O-cyclohexylidene-4'-(hydroxymethyl)uridine；1-[(3aS,6R,6aR)-4,4-bis(hydroxymethyl)spiro[6,6a-dihydro-3aH-furo[3,4-d][1,3]dioxole-2,1'-cyclohexane]-6-yl]pyrimidine-2,4-dione
• CAS: 63592-89-2
• 化学式: C₁₆H₂₂N₂O₇
• 分子量: 354.36
• InChiKey: GCZTWPLJJVENJL-FRRDWIJNSA-N

物化性质

• 密度：
  1.51±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  118
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  O^2'_,O3'-cyclohexane-1,1-diyl-4'-hydroxymethyl-uridine 在 palladium on activated charcoal 吡啶 、 4-二甲氨基吡啶 、 硫酸氢铵 、 N-溴代丁二酰亚胺(NBS) 、 sodium azide 、 氢气 、 sodium hexamethyldisilazane 、 四氯化钛 、 sodium cyanoborohydride 、 三氟乙酸 、 zinc(II) chloride 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 水 、 乙腈 为溶剂， 反应 168.17h， 生成 1-[(1R,4R,6R,7S)-4-[[bis(4-methoxyphenyl)phenylmethoxy]methyl]-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptan-6-yl]-5-methylpyrimidine-2,4-dione
  参考文献：
  名称：

  2′-O,4′-C-methylene bridged nucleic acid (2′,4′-BNA)

  摘要：

  For development of ideal antisense and antigene molecules, various chemical modifications of oligonucleotides have been studied. However, despite their importance. there is only limited information available on the tripler-forming ability of the conformationally restricted or locked oligonucleotides. We report herein that 2'-O,4'-C-methylene bridged nucleic acid (2',4'-BNA) modification of tripler-forming oligonucleotide: (TFO) significantly enhances the binding affinity towards target dsDNA. On T, measurements. the triplex with the 2',4'-BNA oligonucleotides were found to be stabilized with DeltaT(m)/modification of +4.3 to + 5 degreesC at pH 6.6 compared to the triplexes with the unmodified oligonucleotide. By means of gel-retardation assay, the binding constant of the 2'.4'-BNA oligonucleotide at pH 7.0 was at least 300-fold higher than that of the natural oligonucleotide. In addition, the 2',4'-BNA oligonucleotide clearly showed the inhibition of the NF-K-B transcription factor (p50)-target dsDNA binding by forming a stable tripler at pH 7.0. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00325-4

文献信息

• LOCKED AND UNLOCKED 2'-O PHOSPHORAMIDITE NUCLEOSIDES, PROCESS OF PREPARATION THEREOF AND OLIGOMERS COMPRISING THE NUCLEOSIDES
  申请人：VAIJAYANTI Anil Kumar

  公开号：US20110196141A1

  公开（公告）日：2011-08-11

  The present invention relates to 2′-O-phosphoramidite of locked nucleoside and unlocked nucleoside, their synthesis and 2′-5′-linked oligomers oligomers comprising the nucleosides to delineate the structural requirements of 2′-5′ RNA/DNA: 3′-5′ RNA duplexes and also for use in antisense applications.

  本发明涉及锁定核苷酸和非锁定核苷酸的2'-O-磷酰胺酰胺，它们的合成以及包含这些核苷酸的2'-5'-连接寡聚物，以确定2'-5' RNA/DNA: 3'-5' RNA双链的结构要求，并且用于反义应用。
• 1-(3,5-O-Alkylidene-2-deoxy-4-C-hydroxymethyl-α-L-threo-pentofuranosyl)uracils
  作者：Hubert Hřebabecký、Miloš Buděšínský、Milena Masojídková、Zdeněk Havlas、Antonín Holý

  DOI：10.1135/cccc19970957

  日期：——

  1-(2,3-O-Cyclohexylidene-4-C-hydroxymethyl-α-L-lyxofuranosyl)uracil (1) was converted in seven steps into 1-(2-deoxy-4-C-hydroxymethyl-α-L-threo-pentofuranosyl)uracil (8) and further into 1-(2-deoxy-4-C-hydroxymethyl-3,5-O-isopropylidene-α-L-threo-pentofuranosyl)uracil (9). Successive benzoylation, removal of the isopropylidene group, reaction with acetaldehyde diethyl acetal, and debenzoylation afforded (R)- and (S)-1-(2-deoxy-3,5-O-ethylidene-4-C-hydroxymethyl-α-L-threo-pentofuranosyl)uracil (10a and 10b, respectively). Reaction of 1-(2-deoxy-4-C-triphenylmethyloxymethyl-α-L-threo-pentofuranosyl)uracil (14) with dichloromethane under conditions of phase transfer, followed by detritylation, afforded 1-(2-deoxy-4-C-hydroxymethyl-3,5-O-methylidene-α-L-threo- pentofuranosyl)uracil (15). Compound 14 was obtained from the derivative 8 by partial silylation, tritylation and desilylation. The absolute configuration of the isomeric ethylidene derivatives 10a and 10b was determined by NMR spectroscopy and the population of the deoxypentofuranose ring conformers was derived from the vicinal coupling constants J(H,H). The obtained results were compared with energy calculations. Neither of the prepared nucleoside analogues was active in vitro against HIV-1 and HIV-2.

  1-(2,3-环己基甲酰基-4-C-羟甲基-α-L-吕克索呋喃核苷)（1）被转化为1-(2-脱氧-4-C-羟甲基-α-L-反式-戊糖呋喃核苷)（8），并进一步转化为1-(2-脱氧-4-C-羟甲基-3,5-O-异丙基-α-L-反式-戊糖呋喃核苷)（9），共经过七步。连续苯甲酰化，去除异丙基基团，与乙醛二乙醇缩醛反应，去苯甲酰基，得到（R）和（S）-1-(2-脱氧-3,5-O-乙基烯基-4-C-羟甲基-α-L-反式-戊糖呋喃核苷)（10a和10b）。1-(2-脱氧-4-C-三苯甲氧基甲基-α-L-反式-戊糖呋喃核苷)（14）与二氯甲烷在相转移条件下反应，随后去三苯甲基基团，得到1-(2-脱氧-4-C-羟甲基-3,5-O-甲基亚甲基-α-L-反式-戊糖呋喃核苷)（15）。化合物14由衍生物8部分硅化，三苯甲基化和去硅化得到。异构乙烯基衍生物10a和10b的绝对构型由NMR光谱确定，去氧核糖环构象的种群从邻近偶合常数J（H，H）中得出。所得结果与能量计算进行比较。制备的两种核苷类似物在体外对HIV-1和HIV-2均不活性。
• Nucleotide analogues
  申请人：——

  公开号：US06043060A1

  公开（公告）日：2000-03-28

  An oligonucleotide analog or an antisense molecule, which is minimally hydrolyzable with an enzyme in vivo, has a high sense strand binding ability, and is easily synthesized, is provided. It is an oligo- or polynucleotide analog containing one or more monomer units being nucleotide analogs of the general formula: ##STR1## where B may be identical or different, and is a pyrimidine or purine nucleic acid base, or a derivative thereof.

  提供了一种寡核苷酸类似物或反义分子，它在体内最小限度地水解酶，具有高的正义链结合能力，并且易于合成。它是一种寡核苷酸或多核苷酸类似物，包含一个或多个单体单位，这些单体单位是通式的核苷酸类似物：##STR1## 其中B可以相同或不同，是嘧啶或嘌呤核酸碱基或其衍生物。
• Synthesis and conformation of 3′-O,4′-C-methyleneribonucleosides, novel bicyclic nucleoside analogues for 2′,5′-linked oligonucleotide modification
  作者：Satoshi Obika、Ken-ichiro Morio、Daishu Nanbu、Takeshi Imanishi

  DOI：10.1039/a704376g

  日期：——

  Novel bicyclic nucleoside analogues 3′-O,4′-C-methyleneribonucleosides 1 are conveniently prepared starting from uridine; the sugar puckering of 1 is found to be nearly in the S-conformation by means of PM3 calculations and 1 H NMR studies.

  新型双环核苷类似物 3-O,4-C-亚甲基核苷 1 可以从尿苷出发方便地制备；通过 PM3 计算和 1 H NMR 研究，发现 1 的糖褶皱几乎呈 S 构象。
• US6043060A
  申请人：——

  公开号：US6043060A

  公开（公告）日：2000-03-28