(2R,3R,4R,5R)-5-(6-(tritylamino)-9H-purin-9-yl)-4-(trityloxy)-2-((trityloxy)methyl)tetrahydrofuran-3-ol | 31085-56-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (2R,3R,4R,5R)-5-(6-(tritylamino)-9H-purin-9-yl)-4-(trityloxy)-2-((trityloxy)methyl)tetrahydrofuran-3-ol
• 英文别名: (2R,3R,4R,5R)-5-[6-(tritylamino)purin-9-yl]-4-trityloxy-2-(trityloxymethyl)oxolan-3-ol
• CAS: 31085-56-0
• 化学式: C₆₇H₅₅N₅O₄
• 分子量: 994.205
• InChiKey: KZIFMRSPCAITKT-SZLADBSWSA-N

物化性质

• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  13.3
• 重原子数：
  76
• 可旋转键数：
  17
• 环数：
  12.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2R,3R,4R,5R)-5-(6-(tritylamino)-9H-purin-9-yl)-4-(trityloxy)-2-((trityloxy)methyl)tetrahydrofuran-3-ol 在 4-二甲氨基吡啶 、 氢氧化钾 、 甲酸 、 三乙胺 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 乙醚 、 二氯甲烷 、 氯仿 、 苯 为溶剂， 反应 30.25h， 生成 9-(3,5-Di-O-benzyl-2-O-triflyl-β-D-ribofuranosyl)adenine
  参考文献：
  名称：

  A synthesis of 9-(2-deoxy-2-fluoro-.beta.-D-arabinofuranosyl)adenine and -hypoxanthine. An effect of C3'-endo to C2'-endo conformational shift on the reaction course of 2'-hydroxyl group with DAST

  摘要：

  O3',O5',N6-Tritrityladenosine (6), 3',5'-di-O-trityl-N1-benzylinosine (15), and 3',5'-di-O-tritylinosine (18) were prepared and subjected to nucleophilic reaction with DAST. Thus, 6 afforded 2'-beta-fluorine-substituted nucleoside 11 along with the isomeric 2-deoxy-2-(N-trityladenin-3-yl)-3,5-di-O-trityl-alpha-D-arabinofuranosyl fluoride (12). Nucleoside 15, under the same treatment with DAST, gave the desired 2'-fluoroarabino derivative 16 exclusively in high yield. Although 18 was converted into the 2'-beta-fluoro product 19 under the similar conditions, the yield was low. A plausible mechanism of formation of 12 is discussed. Deprotection of 11 and 16 afforded the desired 9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)adenine (1) and -hypoxanthine (2), respectively, in high yield. The conformational influence of sugar protecting groups on the rate of nucleophilic substitution against elimination is discussed. Treatment of O3',O5',N1-benzylinosine (20) with DAST afforded only the elimination products 9-(3',5'-di-O-benzyl-beta-D-erythro-pent-2-enofuranosyl)-1-benzylhypoxanthine (22) and 3-(benzyloxy)-2-[(benzyloxy)methyl]furan (23). On the other hand, 9-(3,5-di-O-trityl-beta-D-arabinofuranosyl)adenine (26) (prepared from 6 by triflyation followed by NaOAc treatment and deacetylation) afforded a mixture from which 2'-deoxy-2'-fluoroadenosine (27) and 9-(2-deoxy-3,5-di-O-trityl-D-erythro-pent-1-enofuranosyl)-N6-trityladenine (28) were isolated in 60 and 30% yield, respectively. O2',O5',N6-Tritrityladenosine (7) was selectively detritylated with HCO2H/Et2O to give O2',N6-ditrityladenosine (30), which, upon treatment with benzyl chloride/KOH, afforded 3',5'-di-O-benzyl-O2',N6-ditrityladenosine (31). 9-(3,5-Di-O-benzyl-beta-D-arabinofuranosyl)adenine (35) was prepared from 31 by further detritylation with CF3CO2H/CHCl3 and triflyation followed by NaOAc treatment and deacetylation of the product. Treatment of 35 with DAST followed by hydrogenolytic debenzylation afforded 2'-deoxy-2'-fluoroadenosine (3) in high yield. The three-step synthesis described herein, albeit about 10% overall yield, is far superior to the currently available multistep procedures which give the desired 2'-fluoroarabinosylpurines in much less overall yields.

  DOI：

  10.1021/jo00028a030
• 作为产物：
  描述：

  3,5-O-(1,1,3,3-四异丙基-1,3-二硅氧烷)腺苷 在 2,6-二叔丁基吡啶 、 四丁基氟化铵 、 silver trifluoromethanesulfonate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 26.0h， 生成 (2R,3R,4R,5R)-5-(6-(tritylamino)-9H-purin-9-yl)-4-(trityloxy)-2-((trityloxy)methyl)tetrahydrofuran-3-ol
  参考文献：
  名称：

  LOCKED NUCLEIC ACID CYCLIC DINUCLEOTIDE COMPOUNDS AND USES THEREOF

  摘要：

  本发明提供了高活性的锁定核酸环二核苷酸（LNA-CDN）免疫刺激剂，通过细胞质受体STING（干扰素基因刺激剂）激活DCs。具体而言，本发明的LNA-CDNs以一种组合物的形式提供，该组合物包括一种或多种诱导人类STING依赖型I型干扰素产生的环二核苷酸，其中组合物中的环二核苷酸至少有一个2′, 4′锁定核酸。

  公开号：

  US20190185511A1

文献信息

• Synthesis of 3′-Fluoro-tRNA Analogues for Exploring Non-ribosomal Peptide Synthesis in Bacteria
  作者：Laura Iannazzo、Guillaume Laisné、Matthieu Fonvielle、Emmanuelle Braud、Jean-Philippe Herbeuval、Michel Arthur、Mélanie Etheve-Quelquejeu

  DOI：10.1002/cbic.201402523

  日期：2015.2.9

  Fluorinated aminoacyl‐tRNA analogues: Semisynthetic routes to fluoro analogues of tRNAAla and Ala‐tRNAAla have been developed. These molecules are non‐isomerisable analogues of the substrates of alanyl‐tRNA synthetases and FemX transferases and should provide new insight into substrate recognition by these enzymes.

  氟化氨-酰tRNA类似物：半合成路线的tRNA的氟类似物丙氨酸和Ala-tRNA的丙氨酸已经开发出来。这些分子是丙氨酰-tRNA合成酶和FemX转移酶底物的不可异构类似物，应该为这些酶对底物的识别提供新的见解。
• Nucleotides Part LI. Synthesis and biological activities of (2′-5′)adenylate trimer conjugates with 2′-terminal 3′-<i>O</i>(ω-hydroxyalkyl) and 3′-<i>O</i>-(ω-carboxyalkyl) spacers
  作者：Cornelia Hörndler、Wolfgang Pfleiderer、Robert J. Suhadolnik、Robert J. Suhadolnik、Nicholas F. Muto、Earl E. Henderson、Earl E. Henderson、Ming-Xu Guan

  DOI：10.1002/hlca.19970800313

  日期：1997.5.12

  An efficient strategy for the synthesis of (2′-5′)adenylate trimer conjugates with 2′-terminal 3′-O-(ω-hydroxyalkyl) and 3′-O-(ω-carboxyalkyl) spacers is reported. Npeoc-protected adenosine building blocks 37--40 for phosphoramidite chemistry carrying a 3′-O-[11-(levulinoyloxy)undecyl], 3′-O-2-[2-(levulinoyloxy)ethoxy]ethyl}, 3′-O-[5-(2-cyanoethoxycarbonyl)pentyl], and 3′-O-5-[(9H-fluoren-9-ylmeth

  报道了合成具有2'-末端3'- O-（ω-羟烷基）和3' - O-（ω-羧基烷基）间隔基的（2'-5'）腺苷酸三聚体共轭物的有效策略。Npeoc保护的腺苷结构单元37--40，用于亚磷酰胺化学，带有3'- O- [11-（乙酰氧基氧基）十一烷基]，3'- O- 2- [2-（乙酰氧基氧基）乙氧基]乙基}，3' - ö - [5-（2- cyanoethoxycarbonyl）戊基]，和3'- ö - 5 - [（9 ħ芴-9-基甲氧基）羰基]戊基}部分，分别制备（NPEOC = 2-（ 4-硝基苯基）乙氧基羰基）。虫草素（3'-脱氧腺苷）二聚体1的缩合导致相应的三聚体42、43、47和48。而乙酰丙酰基（lev）和9 H-芴-9-甲基（fm）封闭基团可以选择性地从三聚体42、43和48上裂解掉，产生中间体44、45，和49用于3'-合成ø - （ω-羟基烷基）三聚体53,54和胆固醇缀
• Nucleotides. Part XLVII. Synthesis of 3′-Deoxyadenylyl-(2′-5′)-3′-deoxyadenylyl-(2′-5′)-3′-O-(2-hydroxyethyl)adenosine and 3′-Deoxyadenylyl-(2′-5′)-3′-deoxyadenylyl-(2′-5′)-3′-O-{2-[(cholest-5-en-3β-yloxy)carbonyloxy]ethyl}adenosine: A New Type of (2′-5′)
  作者：Cornelia Hörndler、Wolfgang Pfleiderer

  DOI：10.1002/hlca.19960790314

  日期：1996.5.8

  2-hydroxyethyl moiety in 3′-O-position was attached to the 2′-terminus of a cordycepin (3′-deoxyadenosine) dimer. Coupling was performed by phosphoramidite chemistry using two alternative approaches – condensation of 5′-phosphoramidite 16 with 2′-OH cordycepin dimer 18 and condensation of dimeric cordycepin phosphoramidite 19 with 5′-OH adenosine derivative 15 – of which the latter synthesis worked best (20)

  将适当保护的在3'- O-位带有乙酰基保护的2-羟乙基部分的腺苷衍生物连接至虫草素（3'-脱氧腺苷）二聚体的2'-末端。通过亚磷酰胺化学反应使用两种替代方法进行偶联-5'-亚磷酰胺16与2'-OH虫草素二聚体18的缩合和二聚虫草素亚磷酰胺19与5'-OH腺苷衍生物15的缩合-后一种合成效果最好20）。裂解乙酰基保护基团（21）后，将碳酸胆固醇酯引入间隔基（24的OH）中）。具有或没有胆固醇部分的三聚体21的三聚体24的最终解封分别提供了改性的虫草素缀合物25和23。
• [EN] COMPOSITIONS AND METHODS FOR ACTIVATING "STIMULATOR OF INTERFERON GENE"-DEPENDENT SIGNALLING<br/>[FR] COMPOSITIONS ET PROCÉDÉS D'ACTIVATION DE LA SIGNALISATION DÉPENDANTE DE « STIMULATEUR DE GÈNES D'INTERFÉRON »
  申请人：ADURO BIOTECH INC

  公开号：WO2017075477A8

  公开（公告）日：2018-04-26
• Nucleosides. 164. Studies directed toward the synthesis of 2'-deoxy-2'-substituted arabino nucleosides. 10. Synthesis of 2'-.beta.-fluoro- and 3'-.alpha.-fluoro-substituted guanine nucleosides. Effect of sugar conformational shifts on nucleophilic displacement of the 2'-hydroxy and 3'-hydroxy group with DAST
  作者：Krzysztof W. Pankiewicz、Jacek Krzeminski、Kyoichi A. Watanabe

  DOI：10.1021/jo00052a055

  日期：1992.12

  Tritylation of 2-N-acetyl-6-O-((4-nitrophenyl)ethyl)guanosine (4) with TrCl/DMAP followed by TrCl/AgNO3 afforded a mixture of isomeric 3',5'-di-O-trityl and 2',5'-di-O-trityl derivatives 6 and 7, which were separated on a silica gel column to give 6 and 7 in 40% and 50% yield, respectively. Upon treatment with DAST, 6 was converted into the corresponding 2'-beta-fluoro nucleoside 8 in 43% yield. Deprotection of the 2-N-acetyl group occurred during the reaction. Removal of the 6-O-NPE group from 8 with DBU/pyridine, followed by detritylation with CF3COOH/CHCl3, gave F-ara-G (1b) in good yield. The same treatment of 7 with DAST did not lead to nucleophilic substitution with fluoride ion, but only decomposition took place. Treatment of the 2',5'-di-O-trityl nucleoside 7 with CF3SO2Cl/DMAP in CH2Cl2, followed by PhCO2K/HMPA, afforded the corresponding xylofuranosyl derivative 16 along with 6-O-deprotected nucleoside 19. The 6-O-NPE group was completely removed in the reaction of triflate nucleoside 15 with CH3CO2Na/HMPA. The obtained diacetyl nucleoside 20 under hydrolysis with Et3N/MeOH/H2O gave 9-(2,5-di-O-trityl-beta-D-xylofuranosyl)guanine (22). Upon reaction of derivative 22 with DAST no formation of the desired 3'-fluoro nucleoside 23 was observed, but only decomposition took place. When, however, the triflate nucleoside 15 was treated with CH3COONa in DMF instead of HMPA the corresponding diacetyl nucleoside 17 with intact 6-O-NPE group was obtained. This compound was hydrolyzed with Et3N/MeOH/H2O to give the 2-N-acetyl derivative 18, which was smoothly converted into the desired 3'-alpha-fluoro-substituted nucleoside 24 in 76% yield. Again, removal of the 2-N-acetyl group occurred during the reaction with DAST. Compound 24 was deprotected with DBU/pyridine followed by CF3COOH/CHCl3 to give 3'-fluoro-3'-deoxyguanosine in good yield (3b). In a similar manner the O2,O5,N6-tritrityladenosine (25) was converted into the corresponding 3'-deoxy-3'-fluoroadenosine (3a).