6-fluoro-9-(2-deoxy-β-D-erythro-pentofuranosyl)purine | 51385-48-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 6-fluoro-9-(2-deoxy-β-D-erythro-pentofuranosyl)purine
• 英文别名: (2R,3S,5R)-5-(6-fluoropurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol
• CAS: 51385-48-9
• 化学式: C₁₀H₁₁FN₄O₃
• 分子量: 254.221
• InChiKey: PBMSPCWTXGWZJH-RRKCRQDMSA-N

物化性质

• 沸点：
  544.8±60.0 °C(Predicted)
• 密度：
  1.85±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  93.3
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-fluoro-9-(2-deoxy-β-D-erythro-pentofuranosyl)purine 在 吡啶 、 六甲基二硅氮烷 作用下， 以 乙二醇二甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.75h， 生成 (3R,4R)-N6-(4-(3-hydroxy-1,2,3,4-tetrahydrophenanthrenyl))-3',5'-bis(tert-butyldimethylsilyl)-2'-deoxyadenosine
  参考文献：
  名称：

  Laksman, Mahesh K.; Sayer, Jane M.; Jerina, Donald M., Journal of the American Chemical Society, 1991, vol. 113, # 17, p. 6589 - 6594

  摘要：

  DOI：
• 作为产物：
  描述：

  6-chloropurine-2'-deoxyriboside 在 四丁基二氟三苯硅酸铵 作用下， 以 乙二醇二甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 6-fluoro-9-(2-deoxy-β-D-erythro-pentofuranosyl)purine
  参考文献：
  名称：

  Utilization Of Tetrabutylammonium Triphenyldifluorosilicate (TBAT) In The Synthesis of 6-Fluoropurine Nucleosides

  摘要：

  Tetrabutylammonium triphenydifluorosilicate (TBAT) has been found to be a useful reagent for the conversion of 6-chloropurine nucleosides to 6-fluoropurine derivatives. The 6-chloropurine nucleosides were reacted with trimethylamine to form quaternary trimethylammonium salts which were treated in situ with TBAT in DMF to effect conversion to the 6-fluoro derivatives in yields of 59-72%.

  DOI：

  10.1080/07328319908044885

文献信息

• Synthesis of Mitomycin C and decarbamoylmitomycin C N6 deoxyadenosine-adducts
  作者：Maggie Zheng、Seokjin Hwang、Timothy Snyder、Jake Aquilina、Gloria Proni、Manuel M. Paz、Padmanava Pradhan、Shu-Yuan Cheng、Elise Champeil

  DOI：10.1016/j.bioorg.2019.103280

  日期：2019.11

  biomimetic methods used to generate MC and DMC mononucleoside adducts are cumbersome and very low yielding. Here, we describe the diastereospecific chemical synthesis of both C-1 epimers of MC and DMC deoxyadenosine adducts. The key step of the synthesis involves an aromatic substitution reaction between a 6-fluoropurine 2'-deoxyribonucleoside and appropriately protected stereoisomeric triaminomitosenes

  抗癌药丝裂霉素C（MC）及其类似物脱氨甲酰丝裂霉素C（DMC）是DNA烷基化剂。MC目前在临床中使用，其细胞毒性主要是由于其形成阻碍DNA复制从而阻止癌细胞增殖的链间交联（ICL）的能力。然而，MC和DMC也都能够与DNA产生单加合物。特别是，我们最近发现DMC与MC一样可以与DNA形成脱氧腺苷（dA）单加合物。这些单加合物发挥的生物学作用值得研究。为了探测这些加合物的作用并在从两种药物处理过的培养细胞中提取的DNA的酶消化物中检测到它们，我们需要使用参考化合物，即MC和DMC dA单核苷加合物。先前用于产生MC和DMC单核苷加合物的仿生方法麻烦且产率很低。在这里，我们描述了MC和DMC脱氧腺苷加合物的C-1差向异构体的非对映特异性化学合成。合成的关键步骤涉及6-氟嘌呤2'-脱氧核糖核苷与适当保护的立体异构体三氨基丝氨酸之间的芳族取代反应，以形成在腺嘌呤-米托烯键上具有S或R立体化学构型的
• Synthesis of polycyclic aromatic hydrocarbon 2′-deoxyadenosine analogs
  作者：Maheshkumar Lakshman、Roland E. Lehr

  DOI：10.1016/0040-4039(90)80012-b

  日期：1990.1

  The chemical synthesis of polycyclic aromatic hydrocarbon (PAH) modified 2′-deoxyadenosine analogs has been achieved. Two model adducts, incorporating a naphthalene (Np) and a benzo[a]pyrene (BaP) unit have been prepared.

  已经实现了多环芳烃（PAH）修饰的2'-脱氧腺苷类似物的化学合成。制备了两个模型加合物，其中包含萘（Np）和苯并[a] py（BaP）单元。
• Non-biomimetic route to deoxyadenosine adducts of carcinogenic polycyclic aromatic hydrocarbons
  作者：Seong Jin Kim、Constance M. Harris、Kee-Yong Jung、Masato Koreeda、Thomas M. Harris

  DOI：10.1016/0040-4039(91)80756-v

  日期：1991.10

  Aminotriols are prepared by direct aminolysis of the diol epoxides of polycyclic aromatic hydrocarbons, providing a substantial improvement over literature methods. The condensation of aminotriols with 6-halopurine deoxyribonucleosides provides a regio- and stereospecific synthesis of deoxyadenosine N6 adducts.

  氨基三醇是通过多环芳族烃的二醇环氧化物的直接氨解制备的，与文献方法相比有实质性的改进。氨基三醇与6-卤代嘌呤脱氧核糖核苷的缩合提供了脱氧腺苷N 6加合物的区域和立体特异性合成。
• Synthesis and Assignment of Absolute Configuration to the N6-Deoxyadenosine Adducts Resulting from Cis and Trans Ring-Opening of Phenanthrene 9,10-Oxide
  作者：Mahesh K. Lakshman、Wei Xiao、Jane M. Sayer、Albert M. Cheh、Donald M. Jerina

  DOI：10.1021/jo00086a027

  日期：1994.4

  Reaction of calf thymus DNA with phenanthrene 9,10-oxide in vitro results in alkylation of the exocyclic amino groups of the purine bases. Adducts result from both cis and trans opening of the epoxide. In the present study, structures of the N-6-deoxyadenosine adducts have been unequivocally assigned by synthesis from optically pure cis- and trans-9-amino-10-hydroxy-9,10-dihydrophethrene. Resolution of trans-9-azido-10-hydroxy-9,10-dihydrophenanthrene as its acetate was achieved on a chiral. HPLC column. The early-eluting (-)-enantiomer was assigned (9R,10R)-absolute configuration based on a characteristic negative CD band at 232 nm due to the helicity of its biphenyl chromophore, in combination with a H-1 NMR coupling constant that indicated pseudodiaxial orientation of the substituents at C-9 and C-10. Aminolysis of the ester followed by reduction of the azido group provided the desired, optically active trans (9R,10R) amino alcohol. As a starting material for synthesis of the cis amino alcohol, trans-9-bromo-10-acetoxy-9,10-dihydrophe was resolved by chiral HPLC. As above, the early-eluting (-)-enantiomer was assigned (9R,10R)absolute configuration based on a characteristic negative CD band at 234 nm. Displacement of bromine with inversion of configuration by azide, aminolysis of the ester, and reduction provided optically pure cis-(9S,10R)-9-amino-10-hydroxy-9,10-dihydrophenanthrene. Coupling of the optically active amino alcohols with 6-fluoro-9-(2-deoxy-beta-D-erythro-pentofuranosyl) purine (the 6-fluoro analog of dA) yielded the corresponding N-6-deoxyadenosine adducts. Comparison of CD spectra and HPLC retention times of the synthetic adducts with those of the adducts obtained from calf thymus DNA make it possible to assign unambiguously the structures of the DNA adducts.
• A Rapid, High-Yield Method for 5′-Hydroxyl Protection in Very Reactive and Amino Group Modified Nucleosides Using Dimethoxytrityl Tetrafluoroborate
  作者：Mahesh K. Lakshman、Barbara Zajc

  DOI：10.1080/07328319608002032

  日期：1996.5

  The conventional method for 4,4'-dimethoxytrityl (DMT) etherification of the 5'-hydroxyl termini in deoxynucleosides that are either highly reactive or those bearing modifications at the exocyclic amino group can be quite problematic, and in several cases the yields are at best mediocre. Herein, we report a rapid, convenient and general procedure for the facile 5'-hydroxyl protection of these nucleosides in exceptionally high yields using DM(+)BF(4)(.). This reagent is particularly useful for the preparation of 5'-O-DMT ethers of nucleosides that are either synthetically valuable or for those that undergo degradation under standard conditions.