3-acetylphenyl 2-cyanoethyl N,N-diisopropyl phosphoramidite | 180262-51-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-acetylphenyl 2-cyanoethyl N,N-diisopropyl phosphoramidite
• 英文别名: 3-[(3-Acetylphenoxy)-[di(propan-2-yl)amino]phosphanyl]oxypropanenitrile
• CAS: 180262-51-5
• 化学式: C₁₇H₂₅N₂O₃P
• 分子量: 336.371
• InChiKey: XVBJRNIBPHFIOI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  62.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-acetylphenyl 2-cyanoethyl N,N-diisopropyl phosphoramidite 在 ammonium hydroxide 、 sodium hydroxide 、 sodium tetrahydroborate 作用下， 反应 1.0h， 生成 Phosphoric acid 3-(1-hydroxy-ethyl)-phenyl ester (2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethyl ester
  参考文献：
  名称：

  Synthesis and Properties of Combinatorial Libraries of Phosphoramidates

  摘要：

  We have assembled a set of combinatorial libraries of phosphoramidates for pharmacological evaluation. A range of functionalized and unfunctionalized diols, representing a variety of diversity elements, were converted into their corresponding dimethoxytrityl H-phosphonate derivatives which were coupled to each other to produce H-phosphonate dimers and trimers. The H-phosphonate diesters were converted into phosphoramidates by reaction with a wide range of primary and secondary amines. Very large libraries (theoretically, in excess of one million compounds) possessing five sites of diversity were generated for use in our drug discovery program. Smaller libraries with lower molecular weights were also prepared in which only two monomeric units were coupled together and converted into their phosphoramidate derivatives. Methods for the attachment of both radioactive and nonradioactive labels, including (32)phosphorus, tritium, and fluorescein, have been developed. Representative single sequences were also prepared and their chemical properties studied.

  DOI：

  10.1021/jo960192+
• 作为产物：
  描述：

  3-羟基苯乙酮 、 2-氰乙基N,N-二异丙基氯亚磷酰胺 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以64%的产率得到3-acetylphenyl 2-cyanoethyl N,N-diisopropyl phosphoramidite
  参考文献：
  名称：

  Synthesis and Properties of Combinatorial Libraries of Phosphoramidates

  摘要：

  We have assembled a set of combinatorial libraries of phosphoramidates for pharmacological evaluation. A range of functionalized and unfunctionalized diols, representing a variety of diversity elements, were converted into their corresponding dimethoxytrityl H-phosphonate derivatives which were coupled to each other to produce H-phosphonate dimers and trimers. The H-phosphonate diesters were converted into phosphoramidates by reaction with a wide range of primary and secondary amines. Very large libraries (theoretically, in excess of one million compounds) possessing five sites of diversity were generated for use in our drug discovery program. Smaller libraries with lower molecular weights were also prepared in which only two monomeric units were coupled together and converted into their phosphoramidate derivatives. Methods for the attachment of both radioactive and nonradioactive labels, including (32)phosphorus, tritium, and fluorescein, have been developed. Representative single sequences were also prepared and their chemical properties studied.

  DOI：

  10.1021/jo960192+

文献信息

• Non-nucleotide phosphorus ester oligomers
  申请人：Genzyme Corporation

  公开号：US06008398A1

  公开（公告）日：1999-12-28

  A phosphorus ester oligomer having the structure: wherein A can be the same or different in each monomeric unit and each is independently selected from the group consisting of oxygen, sulfur, lower alkyl, substituted or unsubstituted alkylamino, substituted or unsubstituted arylamino and aminoalkyl; B.sub.1 and B.sub.2 can be the same or different and each is independently selected from hydrogen, lower alkyl, a labeling group, a protecting group, a phosphoramidate or a phosphomonoester; R.sub.1 can be the same or different in each monomeric unit, and in at least one of the non-nucleotide monomeric units, R.sub.1 is independently selected from the group consisting of (i) a non-vicinal diol attached to a hydrogen bond donor functionality; (ii) a hydrogen bond acceptor selected from an ether; (iii) a non-vicinal diol attached to a hydrophobic functionality or a vicinal diol attached to an aliphatic or alicyclic hydrophobic functionality (iv) a diol attached to a ring substituted anionic functionality and (v) a cationic moiety attached to a non-vicinal or alicyclic diol, any of which can further include a detectable label, and n is at least two. Preferred R.sub.1 moieties include condensation products of alicyclic diols and polycyclic diols; also the non-nucleotide monomers thereof, and the use of the oligomers as selective target-binding compounds.

  一种具有以下结构的磷酸酯寡聚体：其中A可以在每个单体单位中相同或不同，并且每个A都是独立地从以下组中选择的：氧，硫，较低的烷基，取代或未取代的烷基氨基，取代或未取代的芳基氨基和氨基烷基；B.sub.1和B.sub.2可以相同或不同，并且每个B.sub.1和B.sub.2都是独立地从氢，较低的烷基，标记基团，保护基团，磷酰胺酸盐或磷酸单酯中选择的；R.sub.1可以在每个单体单位中相同或不同，在至少一个非核苷单体单位中，R.sub.1独立地从以下组中选择：（i）连接到氢键供体官能团的非邻二醇；（ii）从醚中选择的氢键受体；（iii）连接到疏水官能团的非邻二醇或连接到脂肪族或脂环族疏水官能团的邻二醇；（iv）连接到环取代的负离子官能团的二醇；和（v）连接到非邻或脂环二醇的阳离子基团，其中任何一个都可以进一步包括可检测的标记，n至少为2。首选的R.sub.1基团包括脂环二醇和多环二醇的缩合产物；以及其非核苷单体，以及将寡聚体用作选择性靶向结合化合物。
• NON-NUCLEOTIDE PHOSPHOROUS ESTER OLIGOMERS
  申请人：PHARMAGENICS, INC.

  公开号：EP0880532A1

  公开（公告）日：1998-12-02
• EP0880532A4
  申请人：——

  公开号：EP0880532A4

  公开（公告）日：1999-06-09
• US6008398A
  申请人：——

  公开号：US6008398A

  公开（公告）日：1999-12-28
• [EN] NON-NUCLEOTIDE PHOSPHOROUS ESTER OLIGOMERS<br/>[FR] OLIGOMERES D'ESTER PHOSPHOREUX NON NUCLEOTIDIQUES
  申请人：PHARMAGENICS, INC.

  公开号：WO1997028168A1

  公开（公告）日：1997-08-07

  (EN) A phosphorus ester oligomer having structure (I) wherein A can be the same or different in each monomeric unit and each is independently selected from the group consisting of oxygen, sulfur, lower alkyl, substituted or unsubstituted alkylamino, substituted or unsubstituted arylamino and aminoalkyl; B1 and B2 can be the same or different and each is independently selected from hydrogen, lower alkyl, a labelling group, a protecting group, a phosphoramidate or a phosphomonoester; R1 can be the same or different in each monomeric unit, and in at least one of the non-nucleotide monomeric units, R1 is independently selected from the group consisting of a condensation product of (i) a non-vicinal diol attached to a hydrogen bond donor functionality; (ii) a hydrogen bond acceptor selected from an ether, a purine or pyrimidine substituted 1,2-diol or a disubstituted heterocycle; (iii) a non-vicinal diol attached to a hydrophobic functionality or a vicinal diol attached to an aliphatic or alicyclic hydrophobic functionality; (iv) a diol attached to a ring substituted anionic functionality and (v) a cationic moiety attached to a non-vicinal or alicyclic diol, any of which can further include a detectable label, and n is at least one. Preferred R1 moieties include condensation products of heterocyclic diols, alicyclic diols, and polycyclic diols. Also the non-nucleotide monomers thereof, combinatorial library mixtures of the oligomers and the use of the oligomers as selective target-binding compounds.(FR) L'invention porte sur un oligomère d'ester phosphoreux présentant la structure (I) dans laquelle: A peut être identique ou différent dans chaque unité monomérique, et chacun des A est choisi indépendamment parmi O, S, alkyle inférieur, alkylamino substitué ou non, arylamino et aminoalkyle substitués ou non; B1 et B2 peuvent être identiques ou différents, et chacun choisi indépendamment parmi H, alkyle inférieure, un groupe marqueur, un groupe protecteur, un phosphoramidate ou un phosphomonoester; R1 peut être identique ou différent dans chaque unité monomère, et au moins dans l'une des unités monomères non nucléotidiques, R1 est choisi indépendamment dans un groupe consistant dans les produits de condensation: (i) d'un diol non vicinal lié à une fonction de donneur de liaison hydrogène, (ii) d'un accepteur de liaison hydrogène choisi parmi un éther, un 1,2-diol à substitution purine ou pyrimidine, ou un hétérocycle disubstitué, (iii) d'un diol non vicinal lié à une fonction hydrophobe, ou d'un diol vicinal lié à une fonction hydrophobe aliphatique ou alicyclique, (iv) d'un diol lié à une fonction anionique à substitution de cycle, et (v) d'un fragment cationique lié à un diol non vicinal ou alicyclique, chacun d'eux pouvant de plus comporter un marqueur détectable; et n étant au moins 1. Les fragments R1 préférés comportent des produits de condensation de diols hétérocycliques, alicycliques ou polycycliques. L'invention porte également sur leurs monomères non nucléotidiques, sur des mélanges de bibliothèques combinatoires d'oligomères, et sur l'emploi d'oligomères comme composés se fixant sélectivement à des cibles.