5-fluoro-1-[(3aR,4R,6R,6aR)-tetrahydro-6-(hydroxymethyl)-2,2-dipropylfuro[3,4-d][1,3]dioxol-4-yl]-3-[(E,7R,11R)-3,7,11,15-tetramethylhexadec-2-en-1-yl]pyrimidine-2,4(1H,3H)-dione | 1590381-39-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 5-fluoro-1-[(3aR,4R,6R,6aR)-tetrahydro-6-(hydroxymethyl)-2,2-dipropylfuro[3,4-d][1,3]dioxol-4-yl]-3-[(E,7R,11R)-3,7,11,15-tetramethylhexadec-2-en-1-yl]pyrimidine-2,4(1H,3H)-dione
• 英文别名: 5-fluoro-1-((3aR,4R,6R,6aR)-6-(hydroxymethyl)-2,2-dipropyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-3-((7R,11R)-3,7,11,15-tetramethylhexadec-2-en-1-yl)pyrimidin-2,4(1H,3H)dione；5-fluoro-1-{(3aR,4R,6R,6aR)-6-(hydroxymethyl)-2,2-dipropyltetrahydrofuro[3,4-d] [1,3]dioxol-4-yl}-3-((7R,11R,E)-3,7,11,15-tetramethylhexadec-2-en-1-yl)pyrimidine-2,4(1H,3H)-dione；1-[(3aR,4R,6R,6aR)-6-(hydroxymethyl)-2,2-dipropyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-5-fluoro-3-[(E,7R,11R)-3,7,11,15-tetramethylhexadec-2-enyl]pyrimidine-2,4-dione
• CAS: 1590381-39-7
• 化学式: C₃₆H₆₁FN₂O₆
• 分子量: 636.889
• InChiKey: NMHDTHXLIBIYJU-UWAPZQKXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.6
• 重原子数：
  45
• 可旋转键数：
  20
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  88.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5-fluoro-1-[ (3aR,4R,6R,6aR)-tetrahydro-6-{[(4-methoxyphenyl)(diphenyl)methoxy]methyl}-2,2-dipropylfuro[3,4-d][1,3]dioxol-4-yl]-3-[(7R,11R,)-3,7,11,15-tetramethylhexadec-2-en-1-yl]pyrimidine-2,4(1H,3H)-dione 在 二氯乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 生成 5-fluoro-1-[(3aR,4R,6R,6aR)-tetrahydro-6-(hydroxymethyl)-2,2-dipropylfuro[3,4-d][1,3]dioxol-4-yl]-3-[(E,7R,11R)-3,7,11,15-tetramethylhexadec-2-en-1-yl]pyrimidine-2,4(1H,3H)-dione 、 5-fluoro-1-[(3aR,4R,6R,6aR)-tetrahydro-6-(hydroxymethyl)-2,2-dipropylfuro[3,4-d][1,3]dioxol-4-yl]-3-[(Z,7R,11R)-3,7,11,15-tetramethylhexadec-2-en-1-yl]pyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  5-氟尿嘧啶与萜烯醇的植物醇和神经醇的Mitsunobu反应：核酸的仿生亲脂化的DNA结构单元。

  摘要：

  通过引入2'，3'-O-亚庚基缩酮基（→2），随后进行5'-O-单甲氧基三苯甲基化（→3），对具有抗癌活性的5-氟尿苷（5-FUrd; 1）进行糖保护。将该完全保护的衍生物与植醇（（Z和E）-异构体）或神经醇（（Z）-异构体）进行Mitsunobu反应，得到核萜4a和4b。两者均用在CH 2 Cl 2中的2％Cl 2 CHCOOH 5'-O-脱保护，分别得到化合物5a和5b。将它们分别转化为5'-O-氰基乙基亚磷酰胺6a和6b。此外，重新合成了5-氟尿苷的2'，3'-O-（1-壬基亚癸基）衍生物7a，并在C（5'）处用Eterneon-480fluorphor®（→7b）进行了标记。研究了所得核苷酸在人工双层中的掺入情况，以及它的聚集体形成。另外，制备了两个带有末端植醇烷基化的5-氟尿苷标签的寡核苷酸，已研究了其中之一关于其掺入人工脂质双层中的研究。

  DOI：

  10.1002/cbdv.201300107

文献信息

• 5-Fluoruoracil Derivatives
  申请人：B. Braun Melsungen AG

  公开号：EP2712868A1

  公开（公告）日：2014-04-02

  The present invention relates to a compound represented by formula (I) wherein X is selected from the group of formulae (II) to (IV) wherein R1 is H or C1-C50 chain which may be branched or linear and which may be saturated or unsaturated and which may optionally be interrupted and/or substituted by one or more hetero atom(s) (Het1) and/or functional group(s)(G1); or R1 is a C3-C28 moiety which comprises at least one cyclic structure and which may be saturated or unsaturated and which may optionally be interrupted and/or substituted by one or more hetero atom(s) (Het1) and functional group(s)(G1); R2 is H; or R2 is a Mono-phosphate, Di-phosphate, Tri-phosphate or phosphoramidite moiety; or R2 is -Y-X or -Y-L-Y1- X; Y and Y1 are independently from each other a single bond or a functional connecting moiety, X is a colloid-active compound (CA) or a fluorescence marker (FA) or a polynucleotide moiety having up to 50 nucleotide residues, preferably 10 to 25 nucleotides, especially a polynucleotide having an antisense or antigen effect; L is a linker by means of which Y and X are covalently linked together; R3 and R4 represent independently from each other a C1-C28-alkyl moiety which may optionally be substituted or interrupted by one or more heteroatom(s) and/or functional group(s);or R3 and R4 form a ring having at least 5 members, preferably a ring having 5 to 8 carbon atoms and wherein the ring may be substituted or interrupted by one or more hetero atom(s) and/or functional group(s); or R3 and R4 represent independently from each other a C1-C28-alkyl moiety substituted with one or more moieties selected from the group -Y-X or -Y-L-Y1-X; or R3 and R4 represent independently from each other -Y-X or -Y-L-Y1- X; R5 and R6 represent independently from each other a C1-C28-alkyl moiety which may optionally be substituted or interrupted by one or more heteroatom(s) and/or functional group(s); or R5 and R6 represent independently from each other a C1-C28-alkyl moiety substituted with one or more moieties selected from the group -Y-X or -Y-L-Y1-X; or R5 and R6 form a ring having at least 5 members, preferably a ring having 5 to 18 carbon atoms and wherein the ring may be substituted or interrupted by one or more hetero atom(s) and/or functional group(s); and/or one or more moieties selected from the group -Y-X or -Y-L-Y1- X; R5 and R6 represent independently from each other -Y-X or -Y-L-Y1- X; R7 is a hydrogen atom or -O-R8; R8 is H or C1-C28 chain which may be branched or linear and which may be saturated or unsaturated and which may optionally be interrupted and/or substituted by one or more hetero atom(s) (Het1) and/or functional group(s)(G1); or R8 is -Y-X or -Y-L-Y1- X, with the proviso that R1 and R2 are not both H and/or with the proviso that the compound comprises at least two chains each of which having 4 or more carbon atoms.

  本发明涉及一种由以下公式（I）表示的化合物，其中X选自以下公式（II）至（IV）中的一种：其中R1为H或C1-C50链，可以是支链或直链，可以是饱和或不饱和，并且可能被一个或多个杂原子（Het1）和/或功能基团（G1）中断和/或取代；或R1为包含至少一个环结构的C3-C28基团，可以是饱和或不饱和，并且可能被一个或多个杂原子（Het1）和功能基团（G1）中断和/或取代；R2为H；或R2为单磷酸酯、双磷酸酯、三磷酸酯或磷酰胺基团；或R2为-Y-X或-Y-L-Y1-X；Y和Y1分别独立地为单键或功能连接基团；X为胶体活性化合物（CA）或荧光标记物（FA）或具有最多50个核苷酸残基的多核苷酸基团，优选为10至25个核苷酸，特别是具有反义或抗原效应的多核苷酸；L为连接剂，用于将Y和X共价连接在一起；R3和R4分别独立地表示可以选择性地被一个或多个杂原子和/或功能基团取代或中断的C1-C28烷基基团；或R3和R4形成具有至少5个成员的环，优选为具有5至8个碳原子的环，并且该环可以被一个或多个杂原子和/或功能基团取代或中断；或R3和R4分别独立地表示用一个或多个从-Y-X或-Y-L-Y1-X中选择的基团取代的C1-C28烷基基团；或R3和R4分别独立地表示-Y-X或-Y-L-Y1-X；R5和R6分别独立地表示可以选择性地被一个或多个杂原子和/或功能基团取代或中断的C1-C28烷基基团；或R5和R6分别独立地表示用一个或多个从-Y-X或-Y-L-Y1-X中选择的基团取代的C1-C28烷基基团；或R5和R6形成具有至少5个成员的环，优选为具有5至18个碳原子的环，并且该环可以被一个或多个杂原子和/或功能基团取代或中断；和/或一个或多个从-Y-X或-Y-L-Y1-X中选择的基团；R5和R6分别独立地表示-Y-X或-Y-L-Y1-X；R7为氢原子或-O-R8；R8为H或C1-C28链，可以是支链或直链，可以是饱和或不饱和，并且可能被一个或多个杂原子（Het1）和/或功能基团（G1）中断和/或取代；或R8为-Y-X或-Y-L-Y1-X，但R1和R2不能同时为H，且化合物至少包含两条每条至少有4个或更多碳原子的链。
• 5-FLUOROURIDINE DERIVATIVES
  申请人：B. Braun Melsungen AG

  公开号：EP2900679B1

  公开（公告）日：2020-07-01