O,O-diethyl O-[4-(N-methyl)amino]butyl phosphotriester

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磷酸及其衍生物
• 英文名称: O,O-diethyl O-[4-(N-methyl)amino]butyl phosphotriester
• 英文别名: Diethyl 4-(methylamino)butyl phosphate；diethyl 4-(methylamino)butyl phosphate
• 化学式: C₉H₂₂NO₄P
• 分子量: 239.252
• InChiKey: SHGWNDNJHUMZOM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  15
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  56.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  O,O-diethyl O-[4-(N-methyl)amino]butyl phosphotriester 在 ammonium hydroxide 作用下， 生成 1-甲基吡咯烷 、 磷酸二乙酯铵盐
  参考文献：
  名称：

  The 4-[N-Methyl-N-(2,2,2-trifluoroacetyl)amino]butyl Group as an Alternative to the 2-Cyanoethyl Group for Phosphate Protection in the Synthesis of Oligodeoxyribonucleotides

  摘要：

  The 4-[N-methyl-N-(2,2,2-trifluoroacetyl)amino]butyl group for phosphate protection in the synthesis of oligodeoxyribonucleotides has been developed to completely prevent nucleobase alkylation by acrylonitrile that could potentially occur upon deprotection of the traditional 2-cyanoethyl phosphate protecting group. The properties of this new phosphate protecting group were evaluated using the model phosphotriester 9. The mechanism of phosphate deprotection was studied by treating 9 with concentrated NH4OH. NMR analysis,of the deprotection reaction demonstrated that cleavage of the N-trifluoroacetyl group is rate-limiting. The resulting phosphotriester intermediate 13 was also shown to undergo rapid cyclodeesterification to produce O,O-diethyl phosphate 15 and N-methylpyrrolidine -16 (Scheme 2). Given the facile removal of the 4-[N-methyl-N-(2,2,2-trifluoroacetyl)amino]butyl phosphate protecting group under mild basic conditions, its utilization in oligonucleotide synthesis began with the preparation of the deoxyribonucleoside phosphoramidites 4a-d (Scheme 3). The coupling efficiency of 4a-d and conventional a-cyanoethyl deoxyribonucleoside phosphoramidites 24a-d was then compared in the solid-phase synthesis of the 20-mer d(ATCCGTAGCTAAGGTCATGC). As previously observed in the deprotection of 9, the 4-[N-methyl,N-(2,2,2-trifluoroacetyl)amino]butyl phosphate protecting groups were easily and completely removed from the oligonucleotide by using either concentrated NH4OH or pressurized ammonia gas. Analysis of the deprotected oligomer by polyacrylamide gel electrophoresis (Figure 3) indicated that the phosphoramidites 4a-d are as efficient as the 2-cyanoethyl phosphoramidites 24a-d in the synthesis of the 20-mer. Furthermore, following digestion of the crude 20-mer by snake venom phosphodiesterase and bacterial alkaline phosphatase, HPLC analysis showed complete hydrolysis to individual nucleosides and no detectable nucleobase modification.

  DOI：

  10.1021/jo990835w
• 作为产物：
  描述：

  4-羟基-N-甲基丁烷酰胺 在 吡啶 、 ammonium hydroxide 、 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 反应 26.5h， 生成 O,O-diethyl O-[4-(N-methyl)amino]butyl phosphotriester
  参考文献：
  名称：

  The 4-[N-Methyl-N-(2,2,2-trifluoroacetyl)amino]butyl Group as an Alternative to the 2-Cyanoethyl Group for Phosphate Protection in the Synthesis of Oligodeoxyribonucleotides

  摘要：

  The 4-[N-methyl-N-(2,2,2-trifluoroacetyl)amino]butyl group for phosphate protection in the synthesis of oligodeoxyribonucleotides has been developed to completely prevent nucleobase alkylation by acrylonitrile that could potentially occur upon deprotection of the traditional 2-cyanoethyl phosphate protecting group. The properties of this new phosphate protecting group were evaluated using the model phosphotriester 9. The mechanism of phosphate deprotection was studied by treating 9 with concentrated NH4OH. NMR analysis,of the deprotection reaction demonstrated that cleavage of the N-trifluoroacetyl group is rate-limiting. The resulting phosphotriester intermediate 13 was also shown to undergo rapid cyclodeesterification to produce O,O-diethyl phosphate 15 and N-methylpyrrolidine -16 (Scheme 2). Given the facile removal of the 4-[N-methyl-N-(2,2,2-trifluoroacetyl)amino]butyl phosphate protecting group under mild basic conditions, its utilization in oligonucleotide synthesis began with the preparation of the deoxyribonucleoside phosphoramidites 4a-d (Scheme 3). The coupling efficiency of 4a-d and conventional a-cyanoethyl deoxyribonucleoside phosphoramidites 24a-d was then compared in the solid-phase synthesis of the 20-mer d(ATCCGTAGCTAAGGTCATGC). As previously observed in the deprotection of 9, the 4-[N-methyl,N-(2,2,2-trifluoroacetyl)amino]butyl phosphate protecting groups were easily and completely removed from the oligonucleotide by using either concentrated NH4OH or pressurized ammonia gas. Analysis of the deprotected oligomer by polyacrylamide gel electrophoresis (Figure 3) indicated that the phosphoramidites 4a-d are as efficient as the 2-cyanoethyl phosphoramidites 24a-d in the synthesis of the 20-mer. Furthermore, following digestion of the crude 20-mer by snake venom phosphodiesterase and bacterial alkaline phosphatase, HPLC analysis showed complete hydrolysis to individual nucleosides and no detectable nucleobase modification.

  DOI：

  10.1021/jo990835w

文献信息

• PHOSPHO-ESTER DERIVATIVES AND USES THEREOF
  申请人：RIGAS Basil

  公开号：US20130225529A1

  公开（公告）日：2013-08-29

  Phospho-ester compounds and pharmaceutical compositions thereof administered by the respiratory and other routes for the prevention and/or treatment of lung and brain cancer and precancerous conditions thereof, for the treatment of pain, for the treatment of skin disorders, for treating and/or preventing inflammation-related diseases, and for the treatment and prevention of cancer.

  磷酸酯化合物及其制剂可通过呼吸道及其他途径用于预防和/或治疗肺癌和脑癌及其癌前病变条件，用于疼痛治疗，用于皮肤疾病治疗，用于治疗和/或预防与炎症相关的疾病，以及用于癌症的治疗和预防。
• PRODUCT COMPRISING A NICOTINE-CONTAINING MATERIAL AND AN ANTI-CANCER AGENT
  申请人：Rigas Basil

  公开号：US20140088045A1

  公开（公告）日：2014-03-27

  The present invention provides a composition comprising a nicotine-containing material and an anti-cancer agent usable in the treatment and/or prevention or reduction of the risk of cancer and precancerous conditions as well as for preventing or reducing the risk of cancer recurrence. Furthermore, a composition comprising a nicotine-containing material and an anti-inflammatory agent usable in the treatment and/or prevention or reduction of the risk of inflammation, is provided. The nicotine containing composition can also include both an anti-cancer agent and an anti-inflammatory agent A device for administering the composition of the present invention to subjects can be a cigarette, smoking pipe, smokeless tobacco, electronic cigarette, transdermal patch or the like.
• COMPOUNDS AND COMPOSITIONS FOR USE IN THE PREVENTION AND TREATMENT OF INFLAMMATION-RELATED DISORDERS, PAIN AND FEVER, SKIN DISORDERS, CANCER AND PRECANCEROUS CONDITIONS THEREOF
  申请人：Medicon Pharmaceuticals, Inc.

  公开号：US20140315834A1

  公开（公告）日：2014-10-23

  The present invention provides novel compounds and pharmaceutical compositions for the prevention and/or treatment of cancer and precancerous conditions thereof, for the treatment of pain and fever, for the treatment of skin disorders, and for treating and/or preventing inflammation-related diseases and/or cardiovascular diseases. The compounds of the invention also have analgesic properties and anti-platelet properties. The compounds of the invention may be provided to animals, including mammals and humans, by administering a suitable pharmaceutical dose in a suitable pharmaceutical dosage form. The compounds of the invention have improved efficacy and safety, including higher potency and/or fewer or less severe side effects, than conventional therapies. The compounds of the invention comprise a biologically active moiety or portion (A) that has, or is modified to have at least one carboxyl group. The moiety A is preferably an aliphatic, aromatic or alkylaryl group, preferably derived from a non-steroidal anti-inflammatory drug or NSAID (A). The moiety A is bound to a linker moiety (B) via the carboxyl of group A and a linking atom that is selected from oxygen, nitrogen, and sulphur, to form a carboxylic ester, and amide, or a thioester, bond (X 1 ) between groups A and B. Moiety B is a single bond, an aliphatic group, a substituted benzene, or an alkylene substituted hydrocarbon chain, which in turn is bound to functional moiety Z, which facilitates access of the compound into cells. The moiety Z can comprise, for example, a phosphorous-containing group, a nitrogen-containing group, or a folic acid residue.
• The 4-[<i>N</i>-Methyl-<i>N</i>-(2,2,2-trifluoroacetyl)amino]butyl Group as an Alternative to the 2-Cyanoethyl Group for Phosphate Protection in the Synthesis of Oligodeoxyribonucleotides
  作者：Andrzej Wilk、Andrzej Grajkowski、Lawrence R. Phillips、Serge L. Beaucage

  DOI：10.1021/jo990835w

  日期：1999.10.1

  The 4-[N-methyl-N-(2,2,2-trifluoroacetyl)amino]butyl group for phosphate protection in the synthesis of oligodeoxyribonucleotides has been developed to completely prevent nucleobase alkylation by acrylonitrile that could potentially occur upon deprotection of the traditional 2-cyanoethyl phosphate protecting group. The properties of this new phosphate protecting group were evaluated using the model phosphotriester 9. The mechanism of phosphate deprotection was studied by treating 9 with concentrated NH4OH. NMR analysis,of the deprotection reaction demonstrated that cleavage of the N-trifluoroacetyl group is rate-limiting. The resulting phosphotriester intermediate 13 was also shown to undergo rapid cyclodeesterification to produce O,O-diethyl phosphate 15 and N-methylpyrrolidine -16 (Scheme 2). Given the facile removal of the 4-[N-methyl-N-(2,2,2-trifluoroacetyl)amino]butyl phosphate protecting group under mild basic conditions, its utilization in oligonucleotide synthesis began with the preparation of the deoxyribonucleoside phosphoramidites 4a-d (Scheme 3). The coupling efficiency of 4a-d and conventional a-cyanoethyl deoxyribonucleoside phosphoramidites 24a-d was then compared in the solid-phase synthesis of the 20-mer d(ATCCGTAGCTAAGGTCATGC). As previously observed in the deprotection of 9, the 4-[N-methyl,N-(2,2,2-trifluoroacetyl)amino]butyl phosphate protecting groups were easily and completely removed from the oligonucleotide by using either concentrated NH4OH or pressurized ammonia gas. Analysis of the deprotected oligomer by polyacrylamide gel electrophoresis (Figure 3) indicated that the phosphoramidites 4a-d are as efficient as the 2-cyanoethyl phosphoramidites 24a-d in the synthesis of the 20-mer. Furthermore, following digestion of the crude 20-mer by snake venom phosphodiesterase and bacterial alkaline phosphatase, HPLC analysis showed complete hydrolysis to individual nucleosides and no detectable nucleobase modification.