5-iodo-5'-O-(9-phenylxanthen-9-yl)-2'-deoxyuridine | 146954-83-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 5-iodo-5'-O-(9-phenylxanthen-9-yl)-2'-deoxyuridine
• 英文别名: 1-[(2R,4S,5R)-4-hydroxy-5-[(9-phenylxanthen-9-yl)oxymethyl]oxolan-2-yl]-5-iodopyrimidine-2,4-dione
• CAS: 146954-83-8
• 化学式: C₂₈H₂₃IN₂O₆
• 分子量: 610.405
• InChiKey: LLVUVNAFNRHQIS-FTBPSBKWSA-N

物化性质

• 密度：
  1.72±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  37
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  97.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Fmoc-N-propargylamine 、 5-iodo-5'-O-(9-phenylxanthen-9-yl)-2'-deoxyuridine 在 四(三苯基膦)钯 copper(l) iodide 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以30%的产率得到9H-fluoren-9-ylmethyl N-[3-[1-[(2R,4S,5R)-4-hydroxy-5-[(9-phenylxanthen-9-yl)oxymethyl]oxolan-2-yl]-2,4-dioxopyrimidin-5-yl]prop-2-ynyl]carbamate
  参考文献：
  名称：

  The synthesis of oligonucleotide-polyamide conjugate molecules suitable as PCR primers

  摘要：

  A new class of oligonucleotide-polyamide conjugates having free 3'-termini has been developed. These molecules have the potential to act as multiply-labeled nonradioactive polymerase chain reaction (PCR) primers. The linkage between the oligonucleotide and the polyamide is via a C5-modified deoxyuridine, synthesized in three steps from 5-iodo-2'-deoxyuridine (6). Subsequent palladium-catalyzed coupling of the 5'-O-protected deoxyuridine derivative 7 and the N-protected propargylamines 11 and 12 gave the alkynyl nucleosides 3 and 4, respectively. Both of these were then incorporated onto succinyl-CPG resin by diisopropylcarbodiimide/DMAP-mediated esterifications to give 18 and 19, respectively. Acidolytic removal of all protecting groups, selective acylation at the C5 pendant amine by an activated N(alpha)-(9-fluorenylmethoxycarbonyl) (Fmoc)-protected amino acid followed by reprotection of the 5'-hydroxyl by tritylation with 4,4'-dimethoxytrityl chloride gave the solid support 22. Standard Fmoc solid-phase peptide synthesis on the C5 pendant arm of 22 followed by oligonucleotide synthesis using standard phosphoramidite chemistry on the 5'-hydroxyl gave the desired oligonucleotide-polyamide conjugate 5. A single biotin label was incorporated into the polyamide using the biotinylated lysine synthon 29; this method is expected to be readily applicable for the attachment of multiple biotin residues in a facile and highly-controlled manner. The conjugate 5 was characterized by UV spectroscopy, amino acid analysis, 5'-end labeling with P-32 and reversed-phase C18 HPLC analysis of enzymatic digests. Preliminary experiments with 5 have shown that it is an efficient PCR primer.

  DOI：

  10.1021/jo00060a044
• 作为产物：
  描述：

  9-氯-9-苯基氧杂蒽 、 碘苷 在 4-二甲氨基吡啶 吡啶 作用下， 反应 1.0h， 以70%的产率得到5-iodo-5'-O-(9-phenylxanthen-9-yl)-2'-deoxyuridine
  参考文献：
  名称：

  The synthesis of oligonucleotide-polyamide conjugate molecules suitable as PCR primers

  摘要：

  A new class of oligonucleotide-polyamide conjugates having free 3'-termini has been developed. These molecules have the potential to act as multiply-labeled nonradioactive polymerase chain reaction (PCR) primers. The linkage between the oligonucleotide and the polyamide is via a C5-modified deoxyuridine, synthesized in three steps from 5-iodo-2'-deoxyuridine (6). Subsequent palladium-catalyzed coupling of the 5'-O-protected deoxyuridine derivative 7 and the N-protected propargylamines 11 and 12 gave the alkynyl nucleosides 3 and 4, respectively. Both of these were then incorporated onto succinyl-CPG resin by diisopropylcarbodiimide/DMAP-mediated esterifications to give 18 and 19, respectively. Acidolytic removal of all protecting groups, selective acylation at the C5 pendant amine by an activated N(alpha)-(9-fluorenylmethoxycarbonyl) (Fmoc)-protected amino acid followed by reprotection of the 5'-hydroxyl by tritylation with 4,4'-dimethoxytrityl chloride gave the solid support 22. Standard Fmoc solid-phase peptide synthesis on the C5 pendant arm of 22 followed by oligonucleotide synthesis using standard phosphoramidite chemistry on the 5'-hydroxyl gave the desired oligonucleotide-polyamide conjugate 5. A single biotin label was incorporated into the polyamide using the biotinylated lysine synthon 29; this method is expected to be readily applicable for the attachment of multiple biotin residues in a facile and highly-controlled manner. The conjugate 5 was characterized by UV spectroscopy, amino acid analysis, 5'-end labeling with P-32 and reversed-phase C18 HPLC analysis of enzymatic digests. Preliminary experiments with 5 have shown that it is an efficient PCR primer.

  DOI：

  10.1021/jo00060a044

文献信息

• Oligonucleotide-polyamide conjugates
  申请人：Howard Florey Institute of Experimental Physiology and Medicine

  公开号：US06013434A1

  公开（公告）日：2000-01-11

  This invention relates to novel oligonucleotide-polyamide conjugates preferably having a free 3' hydroxl moiety, and wherein the polyamide is coupled to the oglionucleotide through its carboxyl terminus. A nucleotide polymer conjugate of the formula (I): Nu--NUC--C.dbd.C--X.sup.1 --NH--X.sup.2 --X.sup.3 where X.sup.1 is an unsubstituted or substituted C.sub.1 -C.sub.10 alkylene group, in which one or more carbons may optionally be replaced by --NH--, --O-- or --S--; X.sup.2 is a bond, or an unsubstituted or substituted C.sub.1 -C.sub.20 alkylene group, in which one or more carbons may optionally be replaced by --NH--, --O-- or --S--; the optional substituents in X.sup.1 or X.sup.2 are selected from a variety of groups; X.sup.3 is an amino acid or a polyamide linked via its carboxy terminus; NUC is a nucleoside group of any one of formulas (a), (b), (c), (d) where.fwdarw.indicates the bond to the --C--C-- group in formula (I), and X.sup.4 is a sugar group of formula(e) where the 5' oxygen is linked to Nu, and X.sup.5 and X.sup.6 are each independently H or OR, where R is H, a protecting group, or a solid phase matrix, and Nu is an oligonucleotide. Methods of preparing these compounds, and various uses, for example, as PCR primers, or as a substrate for DNA or RNA polymerase, are also disclosed.

  本发明涉及新型寡核苷酸-聚酰胺共轭物，该共轭物最好具有自由的3'羟基官能团，并且聚酰胺通过其羧基末端与寡核苷酸耦合。公式（I）的核苷酸聚合物共轭物：Nu-NUC-C.dbd.C-X^1-NH-X^2-X^3，其中X^1是未取代或取代的C.sub.1-C.sub.10烷基，其中一个或多个碳原子可以选择性地被--NH--，--O--或--S--取代；X^2是键或未取代或取代的C.sub.1-C.sub.20烷基，其中一个或多个碳原子可以选择性地被--NH--，--O--或--S--取代；X^1或X^2中的可选取代基从各种基团中选择；X^3是氨基酸或通过其羧基末端连接的聚酰胺；NUC是公式（a），（b），（c），（d）中任何一个核苷基团，其中.fwdarw.表示在公式（I）中与--C--C--基团连接，X^4是公式（e）中的糖基，其中5'氧与Nu连接，X^5和X^6各自独立地为H或OR，其中R为H，保护基或固相基质，Nu为寡核苷酸。还公开了制备这些化合物的方法以及各种用途，例如作为PCR引物或作为DNA或RNA聚合酶的底物。
• OLIGONUCLEOTIDE-POLYAMIDE CONJUGATES
  申请人：HOWARD FLOREY INSTITUTE OF EXPERIMENTAL PHYSIOLOGY AND MEDICINE

  公开号：EP0644890B1

  公开（公告）日：2001-12-05
• EP0644890A4
  申请人：——

  公开号：EP0644890A4

  公开（公告）日：1996-03-27
• US6013434A
  申请人：——

  公开号：US6013434A

  公开（公告）日：2000-01-11
• [EN] OLIGONUCLEOTIDE-POLYAMIDE CONJUGATES<br/>[FR] CONJUGUES D'OLIGONUCLEOTIDE-POLYAMIDE
  申请人：HOWARD FLOREY INSTITUTE OF EXPERIMENTAL PHYSIOLOGY AND MEDICINE

  公开号：WO1993024511A1

  公开（公告）日：1993-12-09

  (EN) This invention relates to novel oligonucleotide-polyamide conjugates preferably having a free 3' hydroxyl moiety, and wherein the polyamide is coupled to the oligonucleotide through its carboxyl terminus. A nucleotide polymer conjugate of the formula (I): Nu-NUC-C=C-X1-NH-X2-X3 where X1 is an unsubstituted or substituted C1-C10 alkylene group, in which one or more carbons may optionally be replaced by -NH-, -O- or -S-; X2 is a bond, or an unsubstituted or substituted C1-C20 alkylene group, in which one or more carbons may optionally be replaced by -NH-, -O- or -S-; the optional substituents in X1 or X2 selected from a variety of groups; X3 is an amino acid, or a polyamide linked via its carboxy terminus; NUC is a nucleoside group of any one of formulas (a), (b), (c), (d) where $m(8) indicates the bond to the -C=C- group in formula (I), and X4 is a sugar group of formula (e) where the 5' oxygen is linked to Nu, and X5 and X6 are each independently H or OR, where R is H, a protecting group, or a solid phase matrix, and Nu is an oligonucleotide. Methods of preparing these compounds, and various uses, for example, as PCR primers, or as a substrate for DNA or RNA polymerase, are also disclosed.(FR) Cette invention concerne des nouveaux conjugués d'oligonucléotide-polyamide ayant de préférence une fraction hydroxyle 3' libre et dans lesquels le polyamide est lié à l'oligonucléotide par sa terminaison carboxyle. L'invention concerne également un conjugué polymère nucléotide de la formule (I) Nu-NUC-C=C-X1-NH-X2-X3 dans laquelle X1 représente un groupe alkylène C1-C10 substitué ou non substitué, dans lequel un ou plusieurs atomes de carbone peuvent être optionnellement remplacés par -NH-, -O-, ou -S-; X2 représente une liaison ou un groupe alkylène C1-C20 substitué ou non substitué, dans lequel un ou plusieurs atomes de carbone peuvent être optionnellement remplacés par -NH-, -O- ou -S-; les substituants optionnels dans X1 ou X2 sont sélectionnés parmi divers groupes; X3 représente un acide aminé, ou un polyamide lié par sa terminaison carboxyle; NUC represente un groupe nucléoside selon une des formules: (a), (b), (c), (d) dans lesquelles $m(8) indique la liaison au groupe -C=C- dans la formule (I), et X4 représente un groupe sucre de la formule (e) dans laquelle l'oxygène 5' est lié à Nu et X5 et X6 représentent chacun indépendamment H ou OR, où R représente H, un groupe protecteur ou une matrice en phase solide, et Nu représente un oligonucléotide. Des procédés de préparation de ces composés, leurs utilisations variées, par exemple comme amorces de PCR, ou comme substrat d'ADN ou ARN polymérases, sont également décrits.