2-methoxy-1-β-D-ribofuranosyl-pyrimidine-4-one | 53337-88-5

• 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: 2-methoxy-1-β-D-ribofuranosyl-pyrimidine-4-one
• 英文别名: O²-methyluridine；2-methoxyuridine；2-methoxy-1-β-D-ribofuranosyl-1H-pyrimidin-4-one；O²-methyl-uridine；2-Methoxy-1-β-D-ribofuranosyl-1H-pyrimidin-4-on；1-((2R,3R,4S,5R)-3,4-Dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-methoxypyrimidin-4(1H)-one；1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-methoxypyrimidin-4-one
• CAS: 53337-88-5
• 化学式: C₁₀H₁₄N₂O₆
• 分子量: 258.231
• InChiKey: WBVPJIKOWUQTSD-ZOQUXTDFSA-N

物化性质

• 熔点：
  110-113 °C
• 沸点：
  485.9±55.0 °C(Predicted)
• 密度：
  1.68±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-methoxy-1-β-D-ribofuranosyl-pyrimidine-4-one 在 氨 作用下， 以 甲醇 为溶剂， 反应 8.0h， 以66%的产率得到2-氨基-1-beta-D-呋喃核糖基-4(1H)-嘧啶酮
  参考文献：
  名称：

  Structural Modifications of UMP, UDP, and UTP Leading to Subtype-Selective Agonists for P2Y₂, P2Y₄, and P2Y₆ Receptors

  摘要：

  A large series of derivatives and analogues of the uracil nucleotides UMP, UDP, and UTP with modifications in various positions of the uracil moiety and/or the phosphate groups were synthesized and evaluated at human P2Y(2), P2Y(4), and P2Y(6) receptors. 2-(Ar)alkylthio substitution of UMP and UDP was best tolerated by the P2Y(2) receptor, 2-Phenethylthio-UMP (13e) showed an EC50 value of 1.3 mu M at P2Y(2) and > 70-fold selectivity versus P2Y(4) and P2Y(6) receptors. Substitution of the 2-keto group in UMP by NH (13g, iso-CMP) resulted in the first potent and selective P2Y(4) agonist (EC50 4.98 mu M > 20-fold selective vs P2Y(2) and P2Y(6)). In contrast, :replacement of the 2-keto function in UDP by NH yielded a potent P2Y(2) agonist (12g, iso-CDP, EC50 = 0.604 mu M, > 100-fold selective). In an attempt to obtain metabolically stable UTP analogues, beta,gamma-dichloro- and beta,gamma-difluoro-methylene-UTP derivatives were synthesized. The triphosphate modifications were much better tolerated by P2Y(2), and in some cases also by P2Y(6), than by P2Y(4) receptors. 4-Thio-beta,gamma-difluoromethylene-UTP (14g) was a potent P2Y(2) agonist with an EC50 value of 0.134 mu M and > 50-fold selectivity. N3-Phenacyl-beta,gamma-dichloromethylene-UTP (14b) proved to be a potent P2Y(6) receptor agonist (EC50 0.142 mu M) with high selectivity versus P2Y(4) (50-fold) and moderate selectivity versus P2Y(2) receptors (6-fold).

  DOI：

  10.1021/jm1016297
• 作为产物：
  描述：

  2’,3’,5’-三-O-苯甲酰基-2-硫代尿苷 在 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 2-methoxy-1-β-D-ribofuranosyl-pyrimidine-4-one
  参考文献：
  名称：

  Structural Modifications of UMP, UDP, and UTP Leading to Subtype-Selective Agonists for P2Y₂, P2Y₄, and P2Y₆ Receptors

  摘要：

  A large series of derivatives and analogues of the uracil nucleotides UMP, UDP, and UTP with modifications in various positions of the uracil moiety and/or the phosphate groups were synthesized and evaluated at human P2Y(2), P2Y(4), and P2Y(6) receptors. 2-(Ar)alkylthio substitution of UMP and UDP was best tolerated by the P2Y(2) receptor, 2-Phenethylthio-UMP (13e) showed an EC50 value of 1.3 mu M at P2Y(2) and > 70-fold selectivity versus P2Y(4) and P2Y(6) receptors. Substitution of the 2-keto group in UMP by NH (13g, iso-CMP) resulted in the first potent and selective P2Y(4) agonist (EC50 4.98 mu M > 20-fold selective vs P2Y(2) and P2Y(6)). In contrast, :replacement of the 2-keto function in UDP by NH yielded a potent P2Y(2) agonist (12g, iso-CDP, EC50 = 0.604 mu M, > 100-fold selective). In an attempt to obtain metabolically stable UTP analogues, beta,gamma-dichloro- and beta,gamma-difluoro-methylene-UTP derivatives were synthesized. The triphosphate modifications were much better tolerated by P2Y(2), and in some cases also by P2Y(6), than by P2Y(4) receptors. 4-Thio-beta,gamma-difluoromethylene-UTP (14g) was a potent P2Y(2) agonist with an EC50 value of 0.134 mu M and > 50-fold selectivity. N3-Phenacyl-beta,gamma-dichloromethylene-UTP (14b) proved to be a potent P2Y(6) receptor agonist (EC50 0.142 mu M) with high selectivity versus P2Y(4) (50-fold) and moderate selectivity versus P2Y(2) receptors (6-fold).

  DOI：

  10.1021/jm1016297

文献信息

• Studies on Nucleosides and Nucleotides. VIII. Preparation and Reactions of Triphenylphosphoranediylnucleosides
  作者：Junji Kimura、Kentaro Yagi、Hideyuki Suzuki、Oyo Mitsunobu

  DOI：10.1246/bcsj.53.3670

  日期：1980.12

  The reaction of uridine, N4-benzoylcytidine, guanosine, and N6-p-toluoyladenosine with diethyl azodicarboxylate and triphenylphosphine resulted in the formation of the corresponding 2′,3′-O-(triphenylphosphoranediyl)-cyclonucleosides. On the other hand, adenosine afforded, under similar conditions, 3′,5′-O-(triphenylphosphoranediyl)adenosine (19). The difference can be explained in terms of the acidity

  尿苷、N4-苯甲酰胞苷、鸟苷和 N6-对甲苯酰腺苷与偶氮二羧酸二乙酯和三苯基膦的反应导致形成相应的 2',3'-O-（三苯基正膦二基）-环核苷。另一方面，在类似条件下，腺苷可提供 3',5'-O-（三苯基正膦二基）腺苷 (19)。这种差异可以用核苷碱基部分的酸度来解释。2',3'-O-(三苯基正膦二基)-O2,5'-环尿苷，N4-苯甲酰基-2',3'-O-(三苯基正膦二基)-O2,5'-环胞苷，2',3'的反应-O-(三苯基正膦二基)-N3,5'-环鸟苷或N6-p-toluoyl-2',3'-O-(三苯基正膦二基)-N3,5'-环腺苷与亲核试剂和亲电试剂添加相应的核苷衍生物游离的 2'-和 3'-羟基。因此 2', 3'-O-三苯基正膦二基作为保护基团，在反应产物的后处理过程中很容易去除。19与异氰酸苯酯反应制...
• Synthesis of 2′-O-[(Triisopropylsilyl)oxy]methyl (= tom)-Protected Ribonucleoside Phosphoramidites Containing Various Nucleobase Analogues
  作者：Sébastien Porcher、Stefan Pitsch

  DOI：10.1002/hlca.200590209

  日期：2005.10

  new and shorter synthetic strategies, and sometimes introduced other nucleobase-protecting groups. The 2′-O-tom, 5′-O-(dimethoxytrityl)-protected ribonucleosides N2-acetylisocytidine 5, O2-(diphenylcarbamoyl)-N6-isobutyrylisoguanosine 8, N6-isobutyryl-N2-(methoxyacetyl)purine-2,6-diamine ribonucleoside (= N8-isobutyryl-2-[(methoxyacetyl)amino]adenosine) 11, 5-methyluridine 13, and 5,6-dihydrouridine 15

  报道了旨在有效制备多种2'- O -[（三异丙基甲硅烷基）氧基]甲基（＝ tom）保护的含有修饰的核碱基的核糖核苷亚磷酰胺结构单元的研究的第一结果。所有这里提出的核苷已经掺入到RNA序列通过其他几组，采用2'- ö -tbDMS-或2'- ø -汤姆保护的亚磷酰胺结构单元（TBDMS =（叔丁基）二甲基甲硅烷）。现在，我们优化了现有反应，开发了一些新的和较短的合成策略，有时还引入了其他核碱基保护基团。2'- ø -汤姆，5'- ø - （二甲氧基三苯甲基）保护的核糖核苷Ñ2-乙酰基异胞苷5，O 2-（二苯基氨基甲酰基）-N 6-异丁酰基异鸟苷8，N 6-异丁酰基-N 2-（甲氧基乙酰基）嘌呤-2,6-二胺核糖核苷（=  N 8-异丁酰基-2-[（甲氧基乙酰基）氨基]腺苷）11，5-甲基尿苷13，和5,6-二氢尿苷15通过首先引入核碱基保护基团和二甲氧基三苯甲基，分别，接着2'-制备ø -汤姆基（方案1）。另一个呈现2'-
• Synthesis of S2-Alkyl-2-thiouridines
  作者：Adel A.-H. Abdel-Rahman、Magdy A. Zahran、Ahmed E.-S. Abdel-Megied、Erik B. Pedersen、Claus Nielsen

  DOI：10.1055/s-1996-4187

  日期：1996.2

  5-Substituted S 2-alkyl-2-thiouracils 1a-i were treated with 1,1,1,3,3,3-hexamethyldisilazane and ammonium sulfate at reflux temperature and condensed with 1,2,3,5-tetra-O-acetyl-β-D-ribufuranose in acetonitrile using trimethylsilyl trifluoromethanesulfonate as a catalyst to afford the corresponding protected nucleosides 2a-i which were deprotected with saturated ammonia in methanol. When the nucleobase was substituted with ethoxycarbonyl or cyano groups in the 5-position or was unsubstituted, the deprotection reaction of the nucleoside also resulted in replacement of the methylthio group. This was not observed with 5-alkyl and 5-methoxy substituents.

  5-取代的S 2-烷基-2-硫脲嘧啶1a-i与1,1,1,3,3,3-六甲基二硅氮烷和硫酸铵在回流温度下反应，然后在乙腈中与1,2,3,5-四-O-乙酰基-β-D-核呋喃糖缩合，使用三甲基硅基三氟甲磺酸作为催化剂，得到相应的保护核苷2a-i，这些核苷随后用甲醇中的饱和氨进行去保护。当核碱基在5位上被乙氧羰基或氰基取代或不取代时，核苷的去保护反应也会导致甲硫基团的替换。对于5-烷基和5-甲氧基取代基，则没有观察到这种现象。
• Incorporation of methylated pyrimidine analogues into RNA
  作者：Joseph S. Vyle、Karen J. Young、Jane A. Grasby

  DOI：10.1016/s0040-4039(98)00934-4

  日期：1998.7

  Routes for the preparation of 2′-silyl protected phosphoramidites of the modified nucleosides O2-methyluridine and O4-methyluridine are described. Methodology for the site-specific incorporation of these phosphoramidites into a 25 nucleotide long oligoribonucleotide sequence by solid-phase synthesis is reported.

  描述了制备经修饰的核苷O 2-甲基尿苷和O 4-甲基尿苷的2'-甲硅烷基保护的亚磷酰胺的方法。报道了通过固相合成将这些亚磷酰胺位点特异性掺入25个核苷酸长的寡核糖核苷酸序列的方法学。
• Studies on Nucleosides and Nucleotides. XII. Carbon-Chain Extension at 5′-Position of Ribonucleosides
  作者：Junji Kimura、Hideyuki Kobayashi、Osamu Miyahara、Oyo Mitsunobu

  DOI：10.1246/bcsj.59.869

  日期：1986.3

  presence of diethyl azodicarboxylate and triphenylphosphine selectively at the 5′-position to give the corresponding 4-(nucleosid-5′-yl-aci-nitro)-2,6-di-t-butylcyclohexa-2,5-dienone (aci-nitro ester of nucleoside) in 39–72% yields along with varied amounts of 5′-deoxy-5′-[N,N′-bis(ethoxycarbonyl)hydrazino]nucleosides. By comparison of the reactions of pyrimidine nucleosides having free 2′- and 3′-hydroxyl

  2,6-二叔丁基-4-硝基苯酚与 O2-甲基尿苷、N3-甲基尿苷或 4-三唑基-1-(β-D-呋喃核糖基)-2(1H)-嘧啶酮在偶氮二甲酸二乙酯和三苯基膦选择性地在 5'-位得到相应的 4-(核苷-5'-基-酰基-硝基)-2,6-二-叔丁基环六-2,5-二烯酮 (核苷的酰基-硝基酯) 39–72% 的产率以及不同数量的 5'-deoxy-5'-[N,N'-bis(ethoxycarbonyl)hydrazino] 核苷。通过比较具有游离 2'-和 3'-羟基的嘧啶核苷与其 2',3'-O-异亚丙基衍生物的反应，aci-nitxo酯与 5'-deoxy-5'-肼基核苷受保护基团以及将偶氮二羧酸二乙酯添加到其他反应物溶液所需的时间的影响。同样，N1，N6，2'3'-O-四苯甲酰腺苷以 83% 的产率提供了预期的酸硝基酯。制备的乙酰硝基酯与稳定的正膦如（乙氧基...