fluoro-[[(2S,5R)-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)tetrahydrofuran-2-yl]methoxy]phosphinic acid

• 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: fluoro-[[(2S,5R)-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)tetrahydrofuran-2-yl]methoxy]phosphinic acid
• 英文别名: fluoro-[[(2S,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy]phosphinic acid
• 化学式: C₁₀H₁₄FN₂O₆P
• 分子量: 308.203
• InChiKey: ULUSLSKVTWZHHY-JGVFFNPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2',3'-二脱氧胸苷 在 fluorophosphoric acid tri-n-butylammonium salt 、 mesitylene2-sufonyl-3-nitro-1,2,4-triazole 作用下， 以 吡啶 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.83h， 以64%的产率得到fluoro-[[(2S,5R)-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)tetrahydrofuran-2-yl]methoxy]phosphinic acid
  参考文献：
  名称：

  Synthesis and Antiviral Activity of Some Fluorinated Nucleotide Derivatives

  摘要：

  A number of 3'-fluoro-3'-deoxythymidine 5'-phosphonates and nucleoside 5'-phosphorofluoridates were prepared to study their ability to inhibit replication of HIV-1. Compounds, the 5'-phosphorofluoridates of 3'-azido-3'-deoxythymidine (VIIIc), 3'-fluoro-3'-deoxythymidine (VIIId) and 3'-deoxy-2',3'-didehydrothymidine (VIIIe), exhibit potent anti-HTV-1 activities.

  DOI：

  10.1080/15257779408013244

文献信息

• End selection in directed evolution
  申请人：——

  公开号：US20020146762A1

  公开（公告）日：2002-10-10

  This invention provides methods of obtaining novel polynucleotides and encoded polypeptides by the use of non-stochastic methods of directed evolution (DirectEvolution™). A particular advantage of end-selection-based methods is the ability to recover full-length polynucleotides from a library of progeny molecules generated by mutagenesis methods. These methods include non-stochastic polynucleotide site-saturation mutagenesis (Gene Site Saturation Mutagenesis™) and non-stochastic polynucleotide reassembly (GeneReassembly™). This invention provides methods of obtaining novel enzymes that have optimized physical &/or biological properties. Through use of the claimed methods, genetic vaccines, enzymes, small molecules, and other desirable molecules can be evolved towards desirable properties. For example, vaccine vectors, can be obtained that exhibit increased efficacy for use as genetic vaccines. Vectors obtained by using the methods can have, for example, enhanced antigen expression, increased uptake into a cell, increased stability in a cell, ability to tailor an immune response, and the like. Furthermore, this invention provides methods of obtaining a variety of novel biologically active molecules, in the fields of antibiotics, pharmacotherapeutics, and transgenic traits.

  本发明提供了通过使用非随机定向进化方法（DirectEvolution™）获得新型多核苷酸和编码多肽的方法。基于末端选择的方法的一个特别优势是从诱变方法产生的后代分子库中恢复全长多核苷酸的能力。这些方法包括非随机多核苷酸位点饱和诱变（Gene Site Saturation Mutagenesis™）和非随机多核苷酸重组（GeneReassembly™）。本发明提供了获得具有优化物理和/或生物特性的新型酶的方法。通过使用所要求的方法，基因疫苗、酶、小分子和其他理想分子可以向理想特性进化。例如，获得的疫苗载体可以提高作为基因疫苗使用的效力。例如，使用本发明方法获得的载体可具有增强的抗原表达能力、增强的细胞吸收能力、增强的细胞稳定性、定制免疫反应的能力等。此外，本发明还提供了在抗生素、药物治疗和转基因性状领域获得各种新型生物活性分子的方法。
• Exonuclease-mediated nucleic acid reassembly in directed evolution
  申请人：Diversa Corporation

  公开号：US20030036116A1

  公开（公告）日：2003-02-20

  This invention provides methods of obtaining novel polynucleotides and encoded polypeptides by the use of non-stochastic methods of directed evolution (DirectEvolution™). A particular advantage of exonuclease-mediated reassembly methods is the ability to reassemble nucleic acid strands that would otherwise be problematic to chimerize. Exonuclease-mediated reassembly methods can be used in combination with other mutagenesis methods provided herein. These methods include non-stochastic polynucleotide site-saturation mutagenesis (Gene Site Saturation Mutagenesis™) and non-stochastic polynucleotide reassembly (GeneReassembly™). This invention provides methods of obtaining novel enzymes that have optimized physical &/or biological properties. Through use of the claimed methods, genetic vaccines, enzymes, small molecules, and other desirable molecules can be evolved towards desirable properties. For example, vaccine vectors can be obtained that exhibit increased efficacy for use as genetic vaccines. Vectors obtained by using the methods can have, for example, enhanced antigen expression, increased uptake into a cell, increased stability in a cell, ability to tailor an immune response, and the like. Furthermore, this invention provides methods of obtaining a variety of novel biologically active molecules, in the fields of antibiotics, pharmacotherapeutics, and transgenic traits.

  本发明提供了通过使用非随机定向进化方法（DirectEvolution™）获得新型多核苷酸和编码多肽的方法。外切核酸酶介导的重组方法的一个特别优势是能够重组那些难以嵌合的核酸链。外切核酸酶介导的重组方法可与本文提供的其他诱变方法结合使用。这些方法包括非随机多核苷酸位点饱和诱变（Gene Site Saturation Mutagenesis™）和非随机多核苷酸重组（GeneReassembly™）。本发明提供了获得具有优化物理和/或生物特性的新型酶的方法。通过使用所要求的方法，基因疫苗、酶、小分子和其他理想的分子可以向理想的特性进化。例如，获得的疫苗载体可以提高用作基因疫苗的效力。例如，使用本发明方法获得的载体可具有增强的抗原表达能力、增强的细胞吸收能力、增强的细胞稳定性、定制免疫反应的能力等。此外，本发明还提供了在抗生素、药物治疗和转基因性状领域获得各种新型生物活性分子的方法。
• EXONUCLEASE-MEDIATED NUCLEIC ACID REASSEMBLY IN DIRECTED EVOLUTION
  申请人：——

  公开号：US20040152077A1

  公开（公告）日：2004-08-05

  This invention provides methods of obtaining novel polynucleotides and encoded polypeptides by the use of non-stochastic methods of directed evolution (DirectEvolution™). A particular advantage of exonuclease-mediated reassembly methods is the ability to reassemble nucleic acid strands that would otherwise be problematic to chimerize. Exonuclease-mediated reassembly methods can be used in combination with other mutagenesis methods provided herein. These methods include non-stochastic polynucleotide site-saturation mutagenesis (Gene Site Saturation Mutagenesis™) and non-stochastic polynucleotide reassembly (GeneReassembly™). This invention provides methods of obtaining novel enzymes that have optimized physical &/or biological properties. Through use of the claimed methods, genetic vaccines, enzymes, small molecules, and other desirable molecules can be evolved towards desirable properties. For example, vaccine vectors can be obtained that exhibit increased efficacy for use as genetic vaccines. Vectors obtained by using the methods can have, for example, enhanced antigen expression, increased uptake into a cell, increased stability in a cell, ability to tailor an immune response, and the like. Furthermore, this invention provides methods of obtaining a variety of novel biologically active molecules, in the fields of antibiotics, pharmacotherapeutics, and transgenic traits.

  本发明提供了通过使用非随机定向进化方法（DirectEvolution™）获得新型多核苷酸和编码多肽的方法。外切核酸酶介导的重组方法的一个特别优势是能够重组那些难以嵌合的核酸链。外切核酸酶介导的重组方法可与本文提供的其他诱变方法结合使用。这些方法包括非随机多核苷酸位点饱和诱变（Gene Site Saturation Mutagenesis™）和非随机多核苷酸重组（GeneReassembly™）。本发明提供了获得具有优化物理和/或生物特性的新型酶的方法。通过使用所要求的方法，基因疫苗、酶、小分子和其他理想的分子可以向理想的特性进化。例如，获得的疫苗载体可以提高用作基因疫苗的效力。例如，使用本发明方法获得的载体可具有增强的抗原表达能力、增强的细胞吸收能力、增强的细胞稳定性、定制免疫反应的能力等。此外，本发明还提供了在抗生素、药物治疗和转基因性状领域获得各种新型生物活性分子的方法。
• US6635449B2
  申请人：——

  公开号：US6635449B2

  公开（公告）日：2003-10-21
• US6740506B2
  申请人：——

  公开号：US6740506B2

  公开（公告）日：2004-05-25