二羟丙基腺嘌呤 | 55559-72-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 中文名称: 二羟丙基腺嘌呤
• 英文名称: 9-<(2R)-2,3-dihydroxypropyl>adenine
• 英文别名: (R)-3-(6-amino-9H-purin-9-yl)propane-1,2-diol；3-(6-amino-9H-purin-9-yl)propane-1,2-diol；(R)-9-(2,3-dihydroxypropyl)adenine；(S)-9-(2,3.dihydroxypropyl)adenine；9-(R)-(2,3-dihydroxypropyl)adenine；(S)-DHPA；1,2-Propanediol, 3-(6-amino-9H-purin-9-yl)-, (R)-；(2R)-3-(6-aminopurin-9-yl)propane-1,2-diol
• CAS: 55559-72-3
• 化学式: C₈H₁₁N₅O₂
• 分子量: 209.208
• InChiKey: GSLQFBVNOFBPRJ-RXMQYKEDSA-N

物化性质

• 沸点：
  577.8±60.0 °C(Predicted)
• 密度：
  1.73±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  110
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  二羟丙基腺嘌呤 在 吡啶 、 sodium hydride 、 N,N-二甲基甲酰胺 、 N,N'-二环己基碳二亚胺 作用下， 反应 25.0h， 生成 (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine
  参考文献：
  名称：

  合成光学活性烷基化腺嘌呤衍生物的新方法。

  摘要：

  提出了一种新的手性无环核苷和核苷酸类似物的合成方法，从d（-）-或l（+）-核糖开始。评估了合成化合物对痘病毒家族的抗病毒特性。

  DOI：

  10.1016/j.bmcl.2003.12.107
• 作为产物：
  描述：

  (2R)-3-(6-aminopurin-9-yl)-2-(2-hydroxy-1-methoxyethoxy)propan-1-ol 在 甲酸 作用下， 反应 24.0h， 以95%的产率得到二羟丙基腺嘌呤
  参考文献：
  名称：

  合成光学活性烷基化腺嘌呤衍生物的新方法。

  摘要：

  提出了一种新的手性无环核苷和核苷酸类似物的合成方法，从d（-）-或l（+）-核糖开始。评估了合成化合物对痘病毒家族的抗病毒特性。

  DOI：

  10.1016/j.bmcl.2003.12.107

文献信息

• Synthesis of Chiral Acyclic Nucleosides by Sharpless Asymmetric Dihydroxylation: Access to Cidofovir and Buciclovir
  作者：Tao Qin、Jian-Ping Li、Ming-Sheng Xie、Gui-Rong Qu、Hai-Ming Guo

  DOI：10.1021/acs.joc.8b02442

  日期：2018.12.21

  nucleosides via Sharpless asymmetric dihydroxylation of N-allylpyrimidines or N-alkenylpurines is reported. A range of chiral acyclic nucleosides with two adjacent hydroxyl groups present on the side chains could be produced in good yields (up to 97% yield) and excellent enantioselectivities (90–99% ee). The synthetic utility of the reaction was demonstrated by the catalytic asymmetric synthesis of (S)-Cidofovir

  报道了一种通过N-烯丙基嘧啶或N-烯基嘌呤的Sharpless不对称二羟基化来构建手性无环核苷的有效方法。可以以高收率（最高97％的收率）和出色的对映选择性（90-99％ee）生产一系列在侧链上带有两个相邻羟基的手性无环核苷。通过（S）-西多福韦和（R）-比昔洛韦的催化不对称合成证明了该反应的合成效用。
• Syntheses of Enantiomeric N-(3-Hydroxy-2-phosphonomethoxypropyl) Derivatives of Purine and Pyrimidine Bases
  作者：Antonín Holý

  DOI：10.1135/cccc19930649

  日期：——

  Methods of preparation of N-(3-hydroxy-2-phosphonomethoxypropyl) (HPMP) derivatives of (2S)- and (2R)-configuration (compounds I and XXVII, respectively) are described. The general method starts from the corresponding N-(2,3-dihydroxypropyl) derivatives which were converted either into the (R)-enantiomers XIII by reaction of the base with (R)-glycidol butyrate (XII) in the presence of cesium carbonate and subsequent methanolysis, or into the (S)-enantiomers XI by alkylation of the base with (R)-2,2-dimethyl-4-tosyloxymethyl-1,3-dioxolane (V) in the presence of the same reagent. The amino groups on the heterocyclic base in compounds XI and XIII were benzoylated by silylation followed by reaction with benzoyl chloride and the obtained N-benzoates XV and XVII on reaction with trityl chloride afforded the corresponding 3'-O-trityl derivatives XVI and XVIII. These compounds were condensed with bis(2-propyl) p-sulfonyloxymethylphosphonate (XXIII) in dimethylformamide in the presence of sodium hydride to give the fully protected diesters XXIV and XXVIII. These compounds could be selectively acid-hydrolyzed to remove the trityl group only under formation of compounds XXXV, or methanolyzed and then acid-hydrolyzed to remove the trityl and N-benzoyl groups and lead to compounds XXVI and XXX, or treated with bromotrimethylsilane to remove the trityl and 2-propyl group to give phosphonates of the type XXXI. All the three types of compounds were then converted into free phosphonates of the (S)-series (I) and the (R)-series (XXVII). Derivatives of cytosine (Ia, XXVIIa), adenine (Ib, XXVIIb), 2,6-diaminopurine (Ic, XXVIIc) and guanine (Id, XXVIId) were prepared. Condensation of the partially blocked adenine deriavtive XXXV with the tosyl derivative XXIII and subsequent deprotection afforded 9-(S)-(2,3-diphosphonomethoxy propyl)adenine (XLIII). Reaction of the same compound XXXV or its (R)-enantiomer XXXVIII with diethyl phosphonate , followed by deblocking, afforded 3'-O-phosphoryl derivatives (S)-HPMPA (XXXVII) and (R)-HPMPA (XL).

  描述了制备N-(3-羟基-2-膦甲氧基丙基)（HPMP）衍生物的方法，其中包括（2S）-和（2R）-构型的化合物I和XXVII。一般方法始于相应的N-(2,3-二羟基丙基)衍生物，通过将其转化为（R）-对映体XIII（通过碱与（R）-环氧丙酯（XII）在碳酸铯存在下的反应和随后的甲醇解）或通过在相同试剂存在下，通过碱与（R）-2,2-二甲基-4-对甲苯磺酰氧甲基-1,3-二氧兰（V）烷基化，将其转化为（S）-对映体XI。化合物XI和XIII中的杂环碱基上的氨基被硅烷化后与苯甲酰氯反应，得到的N-苯甲酸酯XV和XVII在与三苯甲基氯反应时生成相应的3'-O-三苯甲基衍生物XVI和XVIII。这些化合物与双(2-丙基)对磺酸氧甲基膦酸酯（XXIII）在二甲基甲酰胺中与氢化钠存在下反应，得到完全保护的二酯体XXIV和XXVIII。这些化合物可以选择性地酸水解以去除三苯甲基基团，仅形成化合物XXXV，或者经甲醇解然后酸水解以去除三苯甲基和N-苯甲酰基团，并导致化合物XXVI和XXX，或者经溴三甲基硅烷处理以去除三苯甲基和2-丙基基团，形成XXXI型膦酸酯。然后将这三种类型的化合物转化为（S）-系列（I）和（R）-系列（XXVII）的自由膦酸酯。制备了胞嘧啶（Ia、XXVIIa）、腺嘌呤（Ib、XXVIIb）、2,6-二氨基嘌呤（Ic、XXVIIc）和鸟嘌呤（Id、XXVIId）的衍生物。部分阻塞的腺嘌呤衍生物XXXV与甲磺酰衍生物XXIII进行缩合反应，随后去保护作用，得到9-(S)-(2,3-二磷酸甲氧基丙基)腺嘌呤（XLIII）。将相同化合物XXXV或其（R）-对映体XXXVIII与二乙基膦酸酯反应，随后去保护，得到3'-O-磷酰化衍生物（S）-HPMPA（XXXVII）和（R）-HPMPA（XL）。
• Enantiomeric radiochemical synthesis of R and S (1-(6-amino-9H-purin-9-yl)-3-fluoropropan-2-yloxy)methylphosphonic acid (FPMPA)
  作者：Dale O. Kiesewetter、Kathleen Knudson、Matt Collins、Sharat Srinivasula、Esther Lim、Michele Di Mascio

  DOI：10.1002/jlcr.1505

  日期：2008.3.30

  Therapy for human immunodeficiency virus (HIV)-infected patients requires chronic multidrug administration. The eventual failure of therapy in some patients has brought into question the tissue concentration of the drugs. With an appropriately radiolabeled compound, we could utilize positron emission tomography to provide quantitative time–activity curves for various tissues. We have developed a fluorine-18 labeled analog of Tenofovir, the active metabolite of Tenofovir DF, a commonly prescribed component of multidrug therapy. Because (1-(6-amino-9H-purin-9-yl)-3-fluoropropan-2-yloxy)methylphosphonic acid (FPMPA) has a chiral center, we prepared both enantiomers and confirmed that the S-isomer exhibited significantly higher antiviral activity than the R-isomer. In viral replication inhibition assays in human MT4 cells infected with SHIVDH12R, S-FPMPA had an IC50 of 1.85 µM (95% CI; 0.8–5.53), while the R-isomer was inactive. An appropriate chiral precursor was prepared to allow the incorporation of fluorine-18. The [18F]FPMPA in racemic, R, or S form was prepared in a 50 min synthesis in 38±5% yield (n=23, corrected for decay). The product was of high radiochemical and enantiomeric purity. The specific activity of the final product was 4.0±1.8 Ci/µmol at EOB (end of bombardment). This product may provide information about drug tissue distribution in animal models under chronic drug treatment. Copyright © 2008 John Wiley & Sons, Ltd.

  针对感染人类免疫缺陷病毒（HIV）患者的治疗需要长期多药物联合管理。一些患者治疗最终失败的问题引发了人们对药物在组织中的浓度的质疑。通过合适的放射性标记化合物，我们可以利用正电子发射断层扫描（PET）为各种组织提供定量的时间—活动曲线。我们开发了一种氟-18标记的替诺福韦类似物，该类是替诺福韦DF的活性代谢物，替诺福韦DF是一种常用的多药物治疗成分。由于(1-(6-氨基-9H-嘌呤-9-基)-3-氟丙基-2-氧甲基)磷酸(FPMPA)具有手性中心，我们制备了两种对映异构体，并确认S-异构体的抗病毒活性显著高于R-异构体。在用SHIVDH12R感染的人MT4细胞的病毒复制抑制实验中，S-FPMPA的IC50为1.85 µM（95% CI；0.8–5.53），而R-异构体则无活性。我们制备了合适的手性前体，以便于氟-18的引入。[18F]FPMPA的外消旋体、R或S形式在38±5%的产率下进行了50分钟的合成（n=23，考虑衰变后修正）。该产品具有高放化学纯度和对映体纯度。最终产品的特定活性在轰击结束时为4.0±1.8 Ci/µmol。该产品可能为动物模型中的药物组织分布提供信息，尤其是在慢性药物治疗下。版权 © 2008 John Wiley & Sons, Ltd.
• A concise and simple synthesis of 1-hydroxy-phenethylamine derivatives: Formal synthesis of naturally occurring norephedrine, virolin and 3-hydroxy-2-phosphonylmethoxypropyl adenine
  作者：S SAHA、P CHAKRABORTY、S C ROY

  DOI：10.1007/s12039-014-0616-x

  日期：2014.5

  A concise and simple synthesis of 1-hydroxy-phenethylamine derivatives has been achieved following classical organic transformations using commercially available chiral pools. The said derivatives were explored for the synthesis of naturally occurring bio-active small molecules. Formal synthesis of norephedrine, virolin and 3-hydroxy-2-phosphonylmethoxypropyl adenine has been demonstrated.

  通过使用市售的手性池进行经典有机转化，实现了 1-羟基苯乙胺衍生物的简便合成。上述衍生物被用于合成天然生物活性小分子。已证明了去甲麻黄碱、紫罗兰素和 3-hydroxy-2-phosphonylmethoxypropyl adenine 的正式合成。
• An enzymatic glycosylation of nucleoside analogues using β-galactosidase from Escherichia coli
  作者：Jiří Blažek、Petr Jansa、Ondřej Baszczyňski、Martin Maxmilian Kaiser、Miroslav Otmar、Marcela Krečmerová、Martin Drančínský、Antonín Holý、Blanka Králová

  DOI：10.1016/j.bmc.2012.02.062

  日期：2012.5

  of β-galactosides of nucleosides and acyclic nucleoside analogues has been developed, using β-galactosidase from Escherichia coli as a catalyst and lactose as a sugar donor. The method is very rapid, feasible and last but not least inexpensive. Its applicability has been proven for a broad variety of possible substrates with respect to its scaling up for preparative use. Five new compounds from a series

  已经开发了一种新的酶法，用于合成核苷和无环核苷类似物的β-半乳糖苷，使用来自大肠杆菌的β-半乳糖苷酶作为催化剂，乳糖作为糖供体。该方法非常快速，可行并且最后但并非最不昂贵。就其用于制备用途的放大而言，其适用性已被证明可用于多种可能的基材。已经从几百毫克的规模制备了一系列核苷和无环核苷类似物的五种新化合物，在所有情况下，都显示出该方法关于反应产率的可再现性和纯化过程的简便性的非常好的结果。