(3R,4R)-4-(adenin-9-yl)-3-hydroxypyrrolidine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: (3R,4R)-4-(adenin-9-yl)-3-hydroxypyrrolidine
• 英文别名: (3R,4R)-4-(6-aminopurin-9-yl)pyrrolidin-3-ol
• 化学式: C₉H₁₂N₆O
• 分子量: 220.234
• InChiKey: KDRLJQRISJDRKH-PHDIDXHHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  102
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3R,4R)-4-(adenin-9-yl)-3-hydroxypyrrolidine 在 三甲基溴硅烷 作用下， 以 水 、 乙腈 为溶剂， 生成 (3R,4R)-(4-(adenin-9-yl)-3-hydroxypyrrolidin-1-yl)methylphosphonic acid
  参考文献：
  名称：

  Pyrrolidine nucleotide analogs with a tunable conformation

  摘要：

  核苷酸类似物中吡咯烷环的构象偏好通过核磁共振和分子建模进行了研究。研究了羟基和核碱基取代基的相对构型以及吡咯烷氮原子的烷基化或酰化对吡咯烷环构象的影响。构象分析结果表明，烷基化/酰化可以有效地用于调节整个伪旋转周期中吡咯烷环的构象。

  DOI：

  10.3762/bjoc.10.205
• 作为产物：
  描述：

  (3R,4R)-4-(adenin-9-yl)-1-N-tert-butyloxycarbonyl-3-(4,4'-dimethoxytrityloxy)pyrrolidine 在 三氟乙酸 作用下， 以 二氯甲烷 、 水 为溶剂， 以84%的产率得到(3R,4R)-4-(adenin-9-yl)-3-hydroxypyrrolidine
  参考文献：
  名称：

  Synthesis of diastereomeric 3-hydroxy-4-pyrrolidinyl derivatives of nucleobases

  摘要：

  The work deals with the synthesis of hydroxypyrrolidine analogs of nucleosides. Starting from the optically pure L- or D-tartaric acid, we improved the synthesis of enantiomeric trans-3,4-dihydroxypyrrolidines and elaborated a procedure for the synthesis of all possible diastereoisomers of 3-hydroxy-4-pyrrolidinyl derivatives of both purine and pyrimidine nucleobases. The prepared compounds were tested for cytostatic and antiviral properties but no significant activity was found. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2006.11.047

文献信息

• Synthesis and hybridization of oligonucleotides modified at AMP sites with adenine pyrrolidine phosphonate nucleotides
  作者：Dominik Rejman、Petr Kočalka、Radek Pohl、Zdeněk Točík、Ivan Rosenberg

  DOI：10.1135/cccc2009022

  日期：——

  Three structurally diverse types of the protected pyrrolidine nucleoside phosphonates were prepared as the monomers for the introduction of pyrrolidine nucleotide units into modified oligonucleotides on the solid phase. Two different chemistries were used for incorporation of modified and natural units: the phosphotriester method for the former, i.e., monomers containing N-phosphonoalkyl and N-phosphonoacyl moieties attached to the pyrrolidine ring nitrogen atom, and phosphoramidite chemistry for the latter. Since the synthesized pyrrolidine nucleoside phosphonic acids are close mimics of the 3′-deoxynucleoside 5′-phosphates, the incorporation of one modified unit into oligonucleotides gives rise to one 2′,5′ internucleotide linkage. A series of nonamers containing two or three modified units, as well as the fully modified adenine 15-mer, were synthesized in reverse order, i.e., from the 5′ to the 3′ end of the strand. The measurement of thermal characteristics of the complexes of modified nonamers with the complementary strand revealed a destabilizing effect of the introduced modification. The modified adenine homooligonucleotide, was found to form the most stable complex with oligothymidylate of all the tested modified oligonucleotides in terms of ΔT_m per modification.

  三种结构多样的保护吡咯烷基核苷酸膦酸酯被制备为单体，用于在固相上引入吡咯烷核苷酸单元到修饰寡核苷酸中。采用两种不同的化学方法来合成修饰和天然单元：前者采用磷酸三酯法，即含有连接到吡咯烷环氮原子的N-膦酸烷基和N-膦酸酰基的单体，后者采用磷酸酰胺化学方法。由于合成的吡咯烷基核苷酸膦酸是3'-去氧核苷酸5'-膦酸的近似物，因此将一个修饰单元引入到寡核苷酸中会产生一个2',5'间核苷酸连接。一系列包含两个或三个修饰单元的九聚体以及完全修饰的腺嘌呤15聚体是以相反的顺序合成的，即从链的5'端到3'端。测量修饰九聚体与互补链形成的复合物的热特性表明，引入修饰会导致复合物不稳定。在所有测试的修饰寡核苷酸中，修饰腺嘌呤同源寡核苷酸与寡胸苷酸形成的复合物具有最稳定的ΔTm值。
• Pyrrolidine N-alkylphosphonates and related nucleotide analogues: synthesis and stereochemistry
  作者：Dominik Rejman、Radek Pohl、Petr Kočalka、Milena Masojídková、Ivan Rosenberg

  DOI：10.1016/j.tet.2009.02.071

  日期：2009.5

  4-dihydroxypyrrolidine derivatives were synthesized and exploited as synthons for the preparation of hydroxypyrrolidine nucleoside phosphonic acids, the 3′-deoxynucleoside 5′-phosphate analogues. Simultaneously, an alternative route, the N-phosphoalkylation of the preformed pyrrolidine nucleosides employing Mannich- and Michael-type reactions, was investigated to obtain desired nucleotide analogues. In contrast to

  合成了N-膦酰基烷基-反式-3,4-二羟基吡咯烷衍生物，并将其用作合成子来制备羟基吡咯烷核苷膦酸，即3'-脱氧核苷5'-磷酸类似物。同时，研究了另一种途径，即利用曼尼希和迈克尔型反应对预先形成的吡咯烷核苷进行N-磷酸烷基化，以获得所需的核苷酸类似物。与后一种方法相反，前一种方法很可能由于亲核置换过程中存在两个可能的S N 2过渡态而形成了两个非对映异构体。通过NMR光谱研究了所制备的核苷酸类似物的立体化学。
• Synthesis of diastereomeric 3-hydroxy-4-pyrrolidinyl derivatives of nucleobases
  作者：Dominik Rejman、Petr Kočalka、Miloš Buděšínský、Radek Pohl、Ivan Rosenberg

  DOI：10.1016/j.tet.2006.11.047

  日期：2007.1

  The work deals with the synthesis of hydroxypyrrolidine analogs of nucleosides. Starting from the optically pure L- or D-tartaric acid, we improved the synthesis of enantiomeric trans-3,4-dihydroxypyrrolidines and elaborated a procedure for the synthesis of all possible diastereoisomers of 3-hydroxy-4-pyrrolidinyl derivatives of both purine and pyrimidine nucleobases. The prepared compounds were tested for cytostatic and antiviral properties but no significant activity was found. (c) 2006 Elsevier Ltd. All rights reserved.
• Pyrrolidine nucleotide analogs with a tunable conformation
  作者：Lenka Poštová Slavětínská、Dominik Rejman、Radek Pohl

  DOI：10.3762/bjoc.10.205

  日期：——

  Conformational preferences of the pyrrolidine ring in nucleotide analogs 7–14 were investigated by means of NMR and molecular modeling. The effect of the relative configuration of hydroxy and nucleobase substituents as well as the effect of the alkylation or acylation of the pyrrolidine nitrogen atom on the conformation of the pyrrolidine ring were studied. The results of a conformational analysis show that the alkylation/acylation can be effectively used for tuning the pyrrolidine conformation over the whole pseudorotation cycle.

  核苷酸类似物中吡咯烷环的构象偏好通过核磁共振和分子建模进行了研究。研究了羟基和核碱基取代基的相对构型以及吡咯烷氮原子的烷基化或酰化对吡咯烷环构象的影响。构象分析结果表明，烷基化/酰化可以有效地用于调节整个伪旋转周期中吡咯烷环的构象。