[(2R,3S,5R)-3-hydroxy-5-[2-(2-methylpropanoylamino)-6-oxo-1H-purin-9-yl]tetrahydrofuran-2-yl]methyl benzoate | 104769-15-5

• 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: [(2R,3S,5R)-3-hydroxy-5-[2-(2-methylpropanoylamino)-6-oxo-1H-purin-9-yl]tetrahydrofuran-2-yl]methyl benzoate
• 英文别名: 5'-O-Benzoyl-2'-deoxy-N2-isobutyrylguanosine；[(2R,3S,5R)-3-hydroxy-5-[2-(2-methylpropanoylamino)-6-oxo-1H-purin-9-yl]oxolan-2-yl]methyl benzoate
• CAS: 104769-15-5
• 化学式: C₂₁H₂₃N₅O₆
• 分子量: 441.444
• InChiKey: ZDOJLIJUPSQFOK-RRFJBIMHSA-N

物化性质

• 熔点：
  117-119 °C
• 密度：
  1.54±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  144
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  [(2R,3S,5R)-3-hydroxy-5-[2-(2-methylpropanoylamino)-6-oxo-1H-purin-9-yl]tetrahydrofuran-2-yl]methyl benzoate 在 吡啶 、 三氟甲磺酸酐 、 碳酸氢钠 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.5h， 生成 N2-isobutyryl-9-(5-O-benzoyl-2-deoxy-β-D-threo-pentofuranosyl)-guanine
  参考文献：
  名称：

  WO2008/143846

  摘要：

  公开号：
• 作为产物：
  描述：

  N2-异丁酰-5'-O-(4,4'-二甲氧基三苯基)-2'-脱氧鸟苷 在 吡啶 、 sodium carbonate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 [(2R,3S,5R)-3-hydroxy-5-[2-(2-methylpropanoylamino)-6-oxo-1H-purin-9-yl]tetrahydrofuran-2-yl]methyl benzoate
  参考文献：
  名称：

  [EN] MODIFIED OLIGOMERIC COMPOUNDS AND USES THEREOF
  [FR] COMPOSÉS OLIGOMÈRES MODIFIÉS ET LEURS UTILISATIONS

  摘要：

  本公开提供了包含至少一个立体非标准核苷酸的修饰寡核苷酸的寡聚化合物。

  公开号：

  WO2020072991A1

文献信息

• Synthesis and evaluation of 3′-azido-2′,3′-dideoxypurine nucleosides as inhibitors of human immunodeficiency virus
  作者：Hong-wang Zhang、Steven J. Coats、Lavanya Bondada、Franck Amblard、Mervi Detorio、Ghazia Asif、Emilie Fromentin、Sarah Solomon、Aleksandr Obikhod、Tony Whitaker、Nicolas Sluis-Cremer、John W. Mellors、Raymond F. Schinazi

  DOI：10.1016/j.bmcl.2009.11.031

  日期：2010.1

  Based on the promising drug resistance profile and potent anti-HIV activity of β-d-3′-azido-2′,3′-dideoxyguanosine, a series of purine modified nucleosides were synthesized by a chemical transglycosylation reaction and evaluated for their antiviral activity, cytotoxicity, and intracellular metabolism. Among the synthesized compounds, several show potent and selective anti-HIV activity in primary lymphocytes

  基于 β- d -3'-azido-2',3'-dideoxyguanosine具有良好的耐药性和强大的抗 HIV 活性，通过化学转糖基化反应合成了一系列嘌呤修饰的核苷，并评估了它们的抗病毒活性、细胞毒性和细胞内代谢。在合成的化合物中，有几种在原代淋巴细胞中显示出有效和选择性的抗 HIV 活性。
• An Alternative Route to the Preparation of (3′ → 5′) Methylene Acetal Linked Di- and Trinucleosides
  作者：Peter J. L. M. Quaedflieg、Cornelis M. Timmers、Gijs A. van der Marel、Esther Kuyl-Yeheskiely、Jacques H. van Boom

  DOI：10.1055/s-1993-25915

  日期：——

  Reaction of deoxynucleoside 3′-O-(methylthiomethyl) acetals 1 with N-iodosuccinimide (NIS) and dibutyl phosphate furnished the corresponding 3′-O-(dibutoxyphosphoryloxy)methyl acetals 6. Condensation of the latter with appropriately protected deoxynucleoside acceptors 3, in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf), afforded in most cases the (3′ → 5′) methylene acetal linked d(B1 Î¥ B2) dimers 4. In addition, TMSOTf-promoted coupling of donor 6 (B1 = CBz) with 3′-O-(methylthiomethyl)thymidine (8) yielded dimer 9. Reaction of 9 with NIS and dibutyl phosphate gave dimer 10, which was applied successfully in the TMSOTf-assisted fusion with acceptors 3(B2 = CBz and ABz), to afford the corresponding trimers d(CÎ¥TÎ¥C) 11 and d(CÎ¥TÎ¥A) 12.

  脱氧核苷3′-O-(甲硫基甲基)乙缩醛1与碘代琥珀酰亚胺(NIS)和二丁基磷酸酯反应，生成相应的3′-O-(二丁氧基磷酰氧)甲基乙缩醛6。后者与适当保护的脱氧核苷受体3在三甲基硅基三氟甲磺酸盐(TMSOTf)的存在下缩合，通常得到(3′ → 5′)亚甲基乙缩醛连接的二聚体d(B1 ∧ B2) 4。此外，TMSOTf促进的供体6 (B1 = CBz)与3′-O-(甲硫基甲基)胸苷(8)的偶联反应生成二聚体9。9与NIS和二丁基磷酸酯反应生成二聚体10，成功用于与受体3(B2 = CBz和ABz)的TMSOTf辅助融合，得到相应的三聚体d(C∧T∧C) 11和d(C∧T∧A) 12。
• Chemoenzymatic Synthesis of 3′-<i>O</i>-Acetal-Protected 2′-Deoxynucleosides as Building Blocks for Nucleic Acid Chemistry
  作者：Tatiana Rodríguez-Pérez、Susana Fernández、Saúl Martínez-Montero、Tania González-García、Yogesh S. Sanghvi、Vicente Gotor、Miguel Ferrero

  DOI：10.1002/ejoc.200901428

  日期：2010.3

  , and tetrahydrofuranyl ethers of 2'-deoxynucleosides, which are useful building blocks for nucleic acid chemistry. Enzymatic benzoylation provides an efficient alternative for protecting the 5'-hydroxy group of the parent nucleosides in a regioselective manner. Subsequently, tetra-hydropyranylation and tetrahydrofuranylation of the 2'-deoxynucleosides at the 3'-hydroxy group were accomplished with

  我们开发了一种简单方便的合成策略，用于制备 2'-脱氧核苷的四氢吡喃基、4-甲氧基-四氢吡喃基和四氢呋喃基醚，它们是核酸化学的有用组成部分。酶促苯甲酰化为以区域选择性方式保护母体核苷的 5'-羟基提供了一种有效的替代方法。随后，以对甲苯磺酸、MgBr 2 或樟脑磺酸为催化剂，对3'-羟基上的2'-脱氧核苷进行四氢吡喃化和四氢呋喃化反应。5'-O-苯甲酰基的脱保护提供了 3'-O-缩醛保护的 2'-脱氧核苷。三步法有望实现受保护核苷的大规模合成。
• Chemo and regioselective acylation of deoxyribonucleosides by means op n,n-bis-(2-oxo-oxazolidin-3-yl) phosphorodiammidic chloride (bopdc)
  作者：Angelo Liguori、Enzo Perri、Giovanni Sindona、Nicola Uccela

  DOI：10.1016/s0040-4020(01)85111-5

  日期：1988.1

  can be obtained by direct acylation of the substrates with carboxylic acid after activation with N,N-bis-(2-oxo-oxazolidin-3-yl) phosphorodiammidic chloride (BOPDC). In the same experimental conditions a chemoselective benzoylation of unprotected deoxyadenosine can be carried out. Nucleotide building blocks have been prepared from the base labile 5 '-protected nucleosides thus obtained.

  在N，N-双-（2-氧代-恶唑烷-3-基）磷二酰胺基氯化物（BOPDC）活化后，通过用羧酸直接将底物酰化，可获得高产率的5'-酰基-脱氧核糖核苷。在相同的实验条件下，可以进行未保护的脱氧腺苷的化学选择性苯甲酰化。已经从由此获得的碱基不稳定的5'-保护的核苷制备了核苷酸构件。
• Oligonucleotide N3.fwdarw.P5' phosphoramidates: triplex DNA formation
  申请人：Lynx Therapeutics, Inc.

  公开号：US05591607A1

  公开（公告）日：1997-01-07

  Modified oligonucleotides 3'-NHP(O)(O.sup.-)O-5' phosphoramidates were synthesized on a solid phase support. The phosphoramidate analogs were found to have significantly increased resistance toward phosphodiesterase digestion. Thermal dissociation experiments demonstrated that these compounds form more stable duplexes than phosphodiesters with complementary DNA and particularly RNA strands. Further, the phosphoramidate analogs can also form stable triplexes with double-stranded DNA target, where under similar conditions parent phosphodiester compounds failed to do so.

  在固相支持上合成了改性寡核苷酸3'-NHP(O)(O.sup.-)O-5'磷酰胺。发现这些磷酰胺类似物对磷酸二酯酶的消化有显着增强的抵抗力。热解离实验表明，这些化合物形成的双链比具有互补DNA和尤其是RNA链的磷酸二酯更稳定。此外，这些磷酰胺类似物还可以在双链DNA靶标上形成稳定的三链结构，在类似条件下，原始的磷酸二酯化合物未能做到。