2',3'-O-isopropylidene-5-bromouridine | 54503-61-6

• 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: 2',3'-O-isopropylidene-5-bromouridine
• 英文别名: 5-bromo-1-((3aR,4R,6R,6aR)-6-(hydroxymethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl) pyrimidine-2,4(1H,3H)-dione；5-bromo-2',3'-O-isopropylidene-uridine；1-[(3aR,4R,6R,6aR)-6-(hydroxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-5-bromopyrimidine-2,4-dione
• CAS: 54503-61-6
• 化学式: C₁₂H₁₅BrN₂O₆
• 分子量: 363.165
• InChiKey: BNOWIBTXEKPNGG-FDDDBJFASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  97.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2',3'-O-isopropylidene-5-bromouridine 在 吡啶 、 咪唑 、 水 、 三氟乙酸 、 三氯氧磷 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 33.0h， 生成 6-cyanouridine 5'-monophosphate
  参考文献：
  名称：

  WO2008/83465

  摘要：

  公开号：
• 作为产物：
  描述：

  (5S,6S)-5-bromo-O⁶,5'-cyclo-5,6-dihydro-2'3'-O-isopropylidineuridine 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 0.08h， 以94%的产率得到2',3'-O-isopropylidene-5-bromouridine
  参考文献：
  名称：

  Hirota, Kosaku; Tomishi, Tetsuo; Sako, Magoichi, Journal of the Chemical Society. Perkin transactions I, 1988, p. 2227 - 2232

  摘要：

  DOI：

文献信息

• OLIGONUCLEOTIDE
  申请人：Kyowa Hakko Kirin Co., Ltd.

  公开号：US20150376611A1

  公开（公告）日：2015-12-31

  The present invention provides an oligonucleotide having improved affinity for AGO2, and the like. The oligonucleotide has a nucleotide residue or a nucleoside residue represented by formula (I) wherein X 1 is an oxygen atom or the like, R 1 is formula (IIA) (wherein R 5A is halogen or the like, and R 6A is a hydrogen atom or the like) or formula (IVA) (wherein Y 3A is a nitrogen atom or the like, and Y 4A is CH or the like), or the like, R 2 is a hydrogen atom, hydroxy, halogen, or optionally substituted lower alkoxy, and R 3 is a hydrogen atom or the like} at the 5′ end thereof, and the nucleotide residue or the nucleoside residue binds to an adjacent nucleotide residue through the oxygen atom at position 3.

  本发明提供了一种具有改善对AGO2亲和力的寡核苷酸等。该寡核苷酸在其5'端具有由式(I)表示的核苷酸残基或核苷酸残基其中X 1 是氧原子或类似物，R 1 是式(IIA)（其中R 5A 是卤素或类似物，而R 6A 是氢原子或类似物）或式(IVA)（其中Y 3A 是氮原子或类似物，而Y 4A 是CH或类似物），或类似物，R 2 是氢原子、羟基、卤素或可选择地取代的较低烷氧基，而R 3 是氢原子或类似物}，并且该核苷酸残基或核苷酸残基通过位于位置3的氧原子与相邻核苷酸残基结合。
• OLIGONUCLEOTIDE HAVING NON-NATURAL NUCLEOTIDE AT 5'-TERMINAL THEREOF
  申请人：Kyowa Hakko Kirin Co., Ltd.

  公开号：US20170354673A1

  公开（公告）日：2017-12-14

  An oligonucleotide having a nucleotide residue or a nucleoside residue represented by formula (I) wherein X 1 is an oxygen atom or the like, R 1 is formula (IIA) (wherein R 5A is halogen or the like, and R 6A is a hydrogen atom or the like), formula (IVA) (wherein Y 3A is a nitrogen atom or the like, and Y 4A is CH or the like), or the like, R 2 is a hydrogen atom, hydroxy, halogen, or optionally substituted lower alkoxy, and R 3 is a hydrogen atom or the like, or formula (VI) (wherein n2 is 1, 2 or 3)} at the 5′ end thereof, wherein the nucleotide residue or the nucleoside residue binds to an adjacent nucleotide residue through the oxygen atom at position 3, is provided.

  具有由式(I)表示的核苷酸残基或核苷酸残基的寡核苷酸其中X1是氧原子或类似物，R1是式(IIA)（其中R5A是卤素或类似物，而R6A是氢原子或类似物），式(IVA)（其中Y3A是氮原子或类似物，而Y4A是CH或类似物），或类似物，R2是氢原子，羟基，卤素，或可选择地取代的较低烷氧基，而R3是氢原子或类似物，或式(VI)（其中n2为1、2或3）}在其5'端，其中核苷酸残基或核苷酸残基通过位于位置3的氧原子与相邻核苷酸残基结合。
• An Unprecedented Twist to ODCase Catalytic Activity
  作者：Masahiro Fujihashi、Angelica M. Bello、Ewa Poduch、Lianhu Wei、Subhash C. Annedi、Emil F. Pai、Lakshmi P. Kotra

  DOI：10.1021/ja054865u

  日期：2005.11.1

  Orotidine-5'-monophosphate decarboxylase (ODCase) has evolved to catalyze a decarboxylation reaction, most probably via a carbanion species at the C6 position of orotidine-5'-monophosphate. We reveal an unusual biochemical pathway of conversion of 6-cyano-uridine-5'-monophosphate by ODCase to barbiturate-5'-monophosphate via perhaps an electrophilic center at the C6 position, leading to inhibition

  Orotidine-5'-monophosphate decarboxylase (ODCase) 已经进化为催化脱羧反应，最有可能是通过 orotidine-5'-monophosphate 的 C6 位置的碳负离子物种。我们揭示了 ODCase 将 6-cyano-uridine-5'-monophosphate 转化为 barbiturate-5'-monophosphate 的一种不寻常的生化途径，可能通过 C6 位置的亲电子中心，导致抑制。ODCase 的这种潜力在设计新型抑制剂时非常有用。
• Lys314 is a Nucleophile in Non-Classical Reactions of Orotidine-5′-Monophosphate Decarboxylase
  作者：Daniel Heinrich、Ulf Diederichsen、Markus Georg Rudolph

  DOI：10.1002/chem.200900397

  日期：2009.7.6

  Molecular versatility: Unusual reactivities such as hydrolysis, nucleophilic aromatic substitution, and addition reactions of human orotidine‐5′‐monophosphate decarboxylase are explained by crystal structures and involve a nucleophilic lysine residue that normally is expected to act solely as a general base (RP=phosphoribosyl, R=CO2H, CN, acetyl, N3, I; R′=OH, SH, acetyl, hydroxymethyl).

  分子多功能性：异常的反应性，例如水解，亲核芳香族取代以及人orotidine-5'-单磷酸脱羧酶的加成反应，都由晶体结构解释，并且涉及亲核赖氨酸残基，通常预期其仅作为一般碱基起作用（RP =磷酸核糖基，R ＝ CO 2 H，CN，乙酰基，N 3，I； R′＝ OH，SH，乙酰基，羟甲基）。
• Pyrimidine S- and N-cyclonucleosides. Synthesis of 6,2'(and 5')-S- and N-cyclouridines. Nucleosides and nucleotides. XXXII.
  作者：SUSUMU SHIBUYA、TOHRU UEDA

  DOI：10.1248/cpb.28.939

  日期：——

  The synthesis of S- and N-cyclouridines, which are "anti"-fixed cyclonucleosides, is described. Bromination of S2, 2'-cyclo-2-thiouridine afforded the 5-bromo derivative. Cleavage of the S2, 2'-cyclo linkage of the 5-bromo derivative with methoxide resulted in the formation of S6, 2'-cyclo-2-O-methyluridine by intramolecular conversion of the S2, 2'-linkage to an S6, 2'-linkage, and this was further converted to the corresponding S6, 2'-cyclo derivatives of uridine, isocytidine and 2-thouridine. Similarly, 2', 3'-O-isopropylidene-S2, 5'-cyclo-2-thiouridine was converted to the 2', 3'-O-isopropylidene-S6, 5'-cyclo derivatives of uridine, isocytidine, and 2-thiouridine. 6-Methylaminouridine was cyclized by treatment with diphenyl carbonate to N6, 2'-cyclo-6-methylaminouridine. Cyclization with triphenylphosphine and diethyl azodicarboxylate gave the N6, 5'-cyclo derivative of 6-methylaminouridine.

  描述了S-和N-环尿苷的合成，这些是“反”固定环核苷。S2，2'-环-2-硫尿苷的溴化反应产出了5-溴衍生物。通过甲氧基对5-溴衍生物的S2，2'-环连接的裂解，实现了S6，2'-环-2-O-甲基尿苷的形成，此过程通过S2，2'-连接转化为S6，2'-连接。此外，进一步转化为相应的尿苷、异尿苷和2-硫尿苷的S6，2'-环衍生物。同样，2'，3'-O-异丙基腈化的S2，5'-环-2-硫尿苷被转化为尿苷、异尿苷和2-硫尿苷的2'，3'-O-异丙基腈化的S6，5'-环衍生物。用二苯碳酸酯处理6-甲氨基尿苷使其环化为N6，2'-环-6-甲氨基尿苷。与三苯基膦和二乙基偶氮二羧酸酯的环化反应生成了6-甲氨基尿苷的N6，5'-环衍生物。