Dioxolane thymine nucleoside

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: Dioxolane thymine nucleoside
• 英文别名: 1-[2-(hydroxymethyl)-1,3-dioxolan-4-yl]-5-methylpyrimidine-2,4-dione
• 化学式: C₉H₁₂N₂O₅
• 分子量: 228.2
• InChiKey: BCAWWPAPHSAUQZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.4
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  88.1
• 氢给体数：
  2
• 氢受体数：
  5

文献信息

• Method for the synthesis of 2',3'-dideoxy-2',3'-didehydronucleosides
  申请人：——

  公开号：US20020198224A1

  公开（公告）日：2002-12-26

  The present invention is an efficient synthetic route to 2′,3′-dideoxy-2′,3 ′-didehydro-nucleosides from available precursors with the option of introducing functionality as needed, such as, the 2′,3′-dideoxy and 2′- or 3′-deoxyribo-nucleoside analogs as well as additional derivatives obtained by subsequent functional group manipulations. Briefly, the present invention discloses a method for the preparation of &bgr;-D and &bgr;-L-2′,3′-dideoxy-2′,3′-didehydro-nucleosides starting from appropriately substituted ribonucleosides in two, optionally three steps: Step (1) a haloacylation, such as haloacetylation, and in particular, bromoacetylation; Step (2) a reductive elimination; and optionally, Step (3) a deprotection. The haloacylation of step (1) can form the 2′-acyl-3′-halonucleoside, the 3′-acyl-2′-halonucleoside, or a mixture thereof.

  本发明提供了一种高效的合成路线，可以从可用的前体物开始合成2'，3'-二脱氧-2'，3'-二脱氢核苷，同时可以根据需要引入功能，例如2'，3'-二脱氧和2'-或3'-脱氧核糖核苷类似物以及通过后续的官能团操作获得的额外衍生物。简而言之，本发明揭示了一种制备β-D和β-L-2'，3'-二脱氧-2'，3'-二脱氢核苷的方法，从适当取代的核糖核苷开始，在两个可选的步骤中进行：步骤（1）卤代酰化，例如卤代乙酰化，特别是溴代乙酰化；步骤（2）还原消除；可选地，步骤（3）去保护基。步骤（1）的卤代酰化可以形成2'-酰基-3'-卤代核苷，3'-酰基-2'-卤代核苷或它们的混合物。
• [EN] ENANTIOMERICALLY PURE beta -L-(-)-1,3-OXATHIOLANE NUCLEOSIDES
  申请人：UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.

  公开号：WO1992010496A1

  公开（公告）日：1992-06-25

  (EN) An asymmetric process for the preparation of enantiomerically pure $g(b)-L-(-)-1,3-oxathiolane-nucleosides that includes the initial preparation of the key chiral intermediates (2R,5R) and (2R,5S)-5-(O-protected)-2-(protected-oxymethyl)-1,3-oxathiolane from 1,6-thioanhydro-L-gulose. The 2R,5(R,S)-5-(O-protected)-2-(protected-oxymethyl)-1,3-oxathiolane is condensed with a desired heterocyclic base, typically a purine or pyrimidine base, to provide the product nucleoside. The synthesis can be used to prepare the pharmaceutically important compound, $g(b)-L-(-)-1-[(2$g(b),4$g(b))-2-(hydroxymethyl)-4-(1,3-thioxolane)]cytosine ($g(b)-L-(-)BCH-189).(FR) Procédé asymétrique pour la préparation de nucléosides de $g(b)-L-(-)-1,3-oxathiolane énantiomériquement purs, consistant à préparer initialement les intermédiaires chiraux-clés (2R,5R) et (2R,5S)-5-(à protection O)-2-oxyméthyle protégé)-1,3-oxathiolane à partir de 1,6-thioanhydro-L-gulose. Le 2R,5(R,S)-5-(à protection O)-2-(oxyméthyle protégé)-1,3-oxathiolane est condensé avec une base hétérocyclique désirée, en général une base purine ou pyrimidine, pour donner le produit nucléoside. La synthèse peut être utilisée pour préparer le composé pharmaceutiquement important $g(b)-L-(-)-1-[(2$g(b),4$g(b))-2-(hydroxyméthyle)-4-(1,3-thioxolane)]cytosine ($g(b)-L-(-)BCH-189).

  这是一种不对称的过程，用于制备对映纯的 $g(b)-L-(-)-1,3-oxathiolane-核苷，包括从1,6-硫代葡萄糖开始制备关键手性中间体（2R,5R）和（2R,5S）-5-（O-保护）-2-（保护氧甲基）-1,3-oxathiolane。2R,5(R,S)-5-（O-保护）-2-（保护氧甲基）-1,3-oxathiolane与所需的杂环碱基（通常是嘌呤或嘧啶碱基）缩合，以提供产物核苷。该合成方法可用于制备重要的药物化合物 $g(b)-L-(-)-1-[(2$g(b),4$g(b))-2-(羟甲基)-4-(1,3-thioxolane)]胞嘧啶（$g(b)-L-(-)BCH-189）。
• Stereoselective synthesis of nucleoside analogues
  申请人：BioChem Pharma Inc.

  公开号：US20030187262A1

  公开（公告）日：2003-10-02

  The invention is a process for stereoselectively producing a dioxolane nucleoside analogue from an anomeric mixture of &bgr; and &agr; anomers represented by the following formula A or formula B: 1 wherein R is selected from the group consisting of C 1-6 alkyl and C 6 - 15 aryl and Bz is benzoyl. The process comprises hydrolyzing said mixture with an enzyme selected from the group consisting of Protease N, Alcalase, Savinase, ChiroCLEC-BL, PS-30, and ChiroCLEC-PC to stereoselectively hydrolyze predominantly one anomer to form a product wherein R 1 is replaced with H. The process also includes the step of separating the product from unhydrolyzed starting material. Additionally, the functional group at the C4 position is stereoselectively replaced with a purinyl or pyrimidinyl or derivative thereof.

  该发明是一种从由以下A或B式表示的β和α异构体的异构体混合物中立体选择性地生产二氧六环核苷类似物的过程：其中R选自由C1-6烷基和C6-15芳基组成的群，Bz为苯甲酰基。该过程包括使用从Protease N、Alcalase、Savinase、ChiroCLEC-BL、PS-30和ChiroCLEC-PC组成的酶中选择的酶水解该混合物，以立体选择性地水解优选的一个异构体，形成其中R1被H取代的产物。该过程还包括将产物与未水解的起始材料分离的步骤。此外，C4位置的官能团体立体选择性地被嘌呤基或嘧啶基或其衍生物取代。
• Synthesis of substituted 1,3-dioxolanes and substituted 1,3-oxathiolanes with antiviral properties
  申请人：BioChem Pharma Inc.

  公开号：US20030087918A1

  公开（公告）日：2003-05-08

  Disclosed are compounds of the formula wherein R 1 is hydrogen or an acyl group having 1 to 16 carbon atoms; R 2 is a purine or pyrimidine base or an analogue or derivative thereof; Z is O, S, S═O or SO 2 ; and pharmaceutically acceptable derivatives thereof. Also described are processes for and intermediates of use in their preparation, pharmaceutical compositions containing these compounds, and the use of these compounds in the antiviral treatment of mammals.

  本发明涉及的化合物的通式为其中R1为氢或具有1至16个碳原子的酰基；R2为嘌呤或嘧啶碱基或其类似物或衍生物；Z为O、S、S═O或SO2；以及其药学上可接受的衍生物。本发明还描述了用于制备这些化合物的过程和中间体、含有这些化合物的制药组合物以及这些化合物在哺乳动物的抗病毒治疗中的使用。
• Method of resolution and antiviral activity of 1,3-oxathiolane nucleoside enantiomers
  申请人：Emory University

  公开号：US20020143194A1

  公开（公告）日：2002-10-03

  A process for the resolution of a racemic mixture of nucleoside enantiomers that includes the step of exposing the racemic mixture to an enzyme that preferentially catalyzes a reaction in one of the enantiomers. The nucleoside enantiomer (−)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane is an effective antiviral agent against HIV, HBV, and other viruses replicating in a similar manner.

  一种用于分离核苷酸对映体混合物的过程，其中包括将混合物暴露于一种偏好催化其中一种对映体反应的酶的步骤。核苷酸对映体（-）-2-羟甲基-5-（5-氟胞嘧啶-1-基）-1,3-噁二唑硫醚是一种有效的抗HIV、HBV和其他以类似方式复制的病毒的药物。