β-Cyanoethyl monochloro-N-morpholinophosphoamidite | 89992-71-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: β-Cyanoethyl monochloro-N-morpholinophosphoamidite
• 英文别名: chloro(2-cyanoethoxy)morpholinophosphine；(2-cyanoethoxy)-N-morpholinochlorophosphoramidite；2-Cyanoethyl 4-morpholinylphosphonochloridite；3-[chloro(morpholin-4-yl)phosphanyl]oxypropanenitrile
• CAS: 89992-71-2
• 化学式: C₇H₁₂ClN₂O₂P
• 分子量: 222.611
• InChiKey: UJSALCRAULVQSC-UHFFFAOYSA-N

物化性质

• 沸点：
  338.3±52.0 °C(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  45.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N2-异丁酰-5'-O-(4,4'-二甲氧基三苯基)-2'-脱氧鸟苷 、 β-Cyanoethyl monochloro-N-morpholinophosphoamidite 以 四氢呋喃 为溶剂， 生成 (2R,3S,5R)-2-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-5-(2-isobutyramido-6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydrofuran-3-yl (2-cyanoethyl) morpholinophosphonite
  参考文献：
  名称：

  β-Cyanoethyl N,N-dialkylamino/N-morpholinomonochloro phosphoamidites, new phosphitylating agents facilitating ease of deprotection and work-up of synthesized oligonucleotides

  摘要：

  DOI：

  10.1016/s0040-4039(00)94216-3
• 作为产物：
  描述：

  N-(三甲基硅基)吗啉 、 2-氰乙基二氯磷酸酯 以 二氯甲烷 为溶剂， 反应 2.0h， 以to give a pale yellow oil (3.87 g, 86%) as a product的产率得到β-Cyanoethyl monochloro-N-morpholinophosphoamidite
  参考文献：
  名称：

  Preparation of nucleoside phosphoramidites and oligonucleotide synthesis

  摘要：

  本发明提供了新型的双功能磷酸化试剂及其在5'-保护核苷酸磷酰胺酯的原位制备和寡核苷酸合成中的应用。根据本发明，双功能磷酸化试剂在中性或弱碱性条件下与核苷酸迅速反应，无需额外的激活步骤。此外，本发明的双功能磷酸化试剂可以在原位选择性地生成相应的核苷酸磷酰胺酯，无需在寡核苷酸合成之前对核苷酸磷酰胺酯进行纯化。最后，本发明的双功能磷酸化试剂相对稳定且易于操作。

  公开号：

  US06340749B1

文献信息

• Synthesis and Conformational Properties of Oligonucleotides Incorporating 2‘-<i>O</i>-Phosphorylated Ribonucleotides as Structural Motifs of Pre-tRNA Splicing Intermediates
  作者：Hiroyuki Tsuruoka、Koh-ichiroh Shohda、Takeshi Wada、Mitsuo Sekine

  DOI：10.1021/jo991097e

  日期：2000.11.1

  blocks 6a-d having the bis(2-cyano-1,1-dimethylethoxy)thiophosphoryl (BCMETP) group were prepared according to our previous phosphorylation procedure. These phosphoramidite units 6a-d were not contaminated with 3'-regioisomers and were successfully applied to solid-phase synthesis to give oligodeoxyuridylates 15, 16 and oligouridylates 21, 22. Self-complementary Drew-Dickerson DNA 12mers 24-28 replaced

  为了合成包含2'-O-磷酸基团的寡核苷酸，根据我们以前的方法制备了具有双（2-氰基-1,1-二甲基乙氧基）硫代磷酰基（BCMETP）的四种核糖核苷3'-亚磷酰胺基结构单元6a-d磷酸化程序。这些亚磷酰胺单元6a-d没有被3'-区域异构体污染，并成功地应用于固相合成，得到寡脱氧尿苷酸酯15、16和寡丁二酸酯21、22。自互补的Drew-Dickerson DNA 12mers 24-28被2取代。类似地合成了在各个位置的'-O-磷酸化的核糖核苷酸。在这些合成中，事实证明，KI（3）是最有效的试剂，用于将最初生成的硫代磷酸酯基团氧化为聚合物载体上的磷酸酯基团。在不使用该转化步骤的情况下，还合成了掺入2'-O-硫代磷酸化尿苷衍生物的三癸氧基尿苷酸17。为了研究2'-磷酸基团对DNA（RNA）双链体的热稳定性和3D结构的影响，对获得的自互补寡核苷酸进行T（m）测量，并对七聚体双链体33-36进行MD模拟。
• Selective synthesis of chlorophosphoramidites using ionic liquids
  作者：Eric J. Amigues、Christopher Hardacre、Gillian Keane、Marie E. Migaud、Sarah E. Norman、William R. Pitner

  DOI：10.1039/b905000k

  日期：——

  sensitivity and impurity issues hampering existing traditional synthetic routes have been eased. Not only can stock chemicals be used without purification, but the reactions may be conducted at room temperature and at high concentrations. Furthermore, reaction times are reduced and rapid addition of reagents is possible whilst retaining tight control over product selectivity. Beyond their role as reaction

  一系列的氯代亚磷酰胺已经被制备出来。 离子液体 并与分子合成的材料进行比较 溶剂。通过使用离子液体作为反应介质，湿气敏感性和杂质问题困扰了现有的传统合成路线，现已得到缓解。不仅可以不使用库存化学品纯化，但是反应可以在室温和高浓度下进行。此外，减少了反应时间，并且可以在保持对产物选择性的严格控制的同时快速添加试剂。除了它们作为反应介质的作用之外，离子液体 还为这些对水分高度敏感的氯代亚磷酰胺提供了独特的存储介质。
• MODIFIED DOUBLE-STRANDED POLYNUCLEOTIDE
  申请人：Koizumi Makoto

  公开号：US20120220649A1

  公开（公告）日：2012-08-30

  The present invention provides a double-stranded polynucleotide having a sense strand polynucleotide consisting of a nucleotide sequence complementary to a target sequence in a target gene, and an antisense strand polynucleotide having a nucleotide sequence complementary to the sense strand polynucleotide, wherein an aryl or heteroaryl compound is bound to a phosphate group at the 5′-end of the antisense strand polynucleotide.

  本发明提供了一种双链聚核苷酸，其具有一个具有与目标基因中的目标序列互补的核苷酸序列的正链聚核苷酸，以及一个具有与正链聚核苷酸互补的核苷酸序列的反义链聚核苷酸，其中一种芳基或杂环芳基化合物结合到反义链聚核苷酸的5'-末端的磷酸基团上。
• 2' ,5' -Oligoadenylate analogs
  申请人：Koizumi Makoto

  公开号：US20050261235A1

  公开（公告）日：2005-11-24

  A 2-5A analog represented by the formula (1): wherein m is 0 or 1; n is 0 to 2; R 1 represents an alkoxy group having from 1 to 6 carbon atoms which may be substituted, an unprotected mercapto group, a mercapto group protected by a nucleic acid synthesis protecting group, or an alkylthio group having from 1 to 4 carbon atoms which may be substituted; R 2 , R 3 , R 4 , R 5 and R 6 represent an unprotected hydroxyl group, a hydroxyl group protected by a nucleic acid synthesis protecting group, an alkoxy group having from 1 to 6 carbon atoms which may be substituted, an unprotected mercapto group, a mercapto group protected by a nucleic acid synthesis protecting group, or an alkylthio group having from 1 to 4 carbon atoms which may be substituted; R 7 represents an oxygen atom, or a —O(CH 2 CH 2 O)q-group, wherein q is 2 to 6; R 8 represents a hydrogen atom, an alkyl group having from 1 to 6 carbon atoms which may be substituted, or a 5′-phosphorylated oligonucleotide analog which has one hydroxyl group removed from the 5′-phosphoric acid group; E 1 , E 2 , E 3 and E 4 represent a naturally occurring or modified nucleic acid unit, or a pharmacologically acceptable salt thereof.

  一种由公式（1）表示的2-5A模拟物，其中m为0或1；n为0至2；R1表示具有1至6个碳原子的烷氧基，可以被取代，未保护的巯基，通过核酸合成保护基保护的巯基，或者具有1至4个碳原子的烷硫基，可以被取代；R2、R3、R4、R5和R6表示未保护的羟基，通过核酸合成保护基保护的羟基，具有1至6个碳原子的烷氧基，可以被取代，未保护的巯基，通过核酸合成保护基保护的巯基，或者具有1至4个碳原子的烷硫基，可以被取代；R7表示氧原子，或者-O(CH2CH2O)q-基团，其中q为2至6；R8表示氢原子，具有1至6个碳原子的烷基，可以被取代，或者从5'-磷酸基团中去除一个羟基的5'-磷酸寡核苷酸类似物；E1、E2、E3和E4表示天然或修饰的核酸单元，或其药理学上可接受的盐。
• Method of treating a tumor or a viral disease by administering a 2' , 5' -oligoadenylate analog
  申请人：Koizumi Makoto

  公开号：US20100035976A1

  公开（公告）日：2010-02-11

  A method of treating a tumor or a viral disease by administering to a human the following 2′,5′-oligoadenylate analog: Wherein m is 0; n is 0 or 1; R 1 is alkoxy substituted by hydroxyl, mercapto, alkylthio substituted by hydroxyl or X 1 —X 2 —X 3 —S—; R 2 , R 3 , R 4 , R 5 and R 6 are hydroxyl, mercapto, alkylthio substituted by hydroxyl or X 1 —X 2 —X 3 —S—; R 7 is oxygen, sulfur, —NH—, or —O(CH 2 CH 2 O)q-, wherein q is 2 to 6, or oxyalkyleneoxy; R 8 is hydrogen or a 5′-phosphorylated oligonucleotide which has one hydroxyl removed from the 5′-phosphoric acid; E 1 is K 2 ; E 2 is K 1 ; E 3 is K 2 or K 3 and E 4 is K 1 , K 2 or K 3 ; K 1 is K 2 is K 3 is B is adeninyl; A is alkylene; D is alkyl or alkenyl; X 1 is alkyl or phenyl; X 2 is —C(═O)O—, —OC(═O)— or —C(═O)S—; and X 3 is alkylene.

  一种通过向人体内注射以下2′，5′-寡腺苷酸类似物来治疗肿瘤或病毒性疾病的方法：其中m为0；n为0或1；R1为烷氧基，被羟基，巯基，被羟基的烷基硫代基或X1—X2—X3—S—取代的烷氧基；R2，R3，R4，R5和R6为羟基，巯基，被羟基的烷基硫代基或X1—X2—X3—S—；R7为氧，硫，—NH—，或—O(CH2CH2O)q-，其中q为2至6，或氧烷氧基；R8为氢或一个5′-磷酸寡核苷酸，其5′-磷酸上有一个羟基被去除；E1为K2；E2为K1；E3为K2或K3，E4为K1，K2或K3；K1，K2和K3为B为腺苷基；A为烷基；D为烷基或烯基；X1为烷基或苯基；X2为—C(═O)O—，—OC(═O)—或—C(═O)S—；X3为烷基。