5'-O-Fluorenylmethoxycarbonyl-thymidine | 83565-25-7

• 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'-O-Fluorenylmethoxycarbonyl-thymidine
• 英文别名: 5'-O-<(9H-fluoren-9-yl)methoxycarbonyl> thymidine；5'-O-[(9H-fluoren-9-yl)-methoxycarbonyl]thymidine；5′-O-Fmoc-thymidine；5'-O-(9-fluorenylmethoxycarbonyl)thymidine；5'-o-Fmoc-thymidine；9H-fluoren-9-ylmethyl [(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl carbonate
• CAS: 83565-25-7
• 化学式: C₂₅H₂₄N₂O₇
• 分子量: 464.475
• InChiKey: HXGJCVZCDDZJJZ-BHDDXSALSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5'-O-Fluorenylmethoxycarbonyl-thymidine 在 四氮唑 、 4-二甲氨基吡啶 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 [(2R,3S,5R)-2-[[[di(propan-2-yl)amino]-[(2R,3S,5R)-2-(9H-fluoren-9-ylmethoxycarbonyloxymethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxyphosphanyl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl] acetate
  参考文献：
  名称：

  Synthesis and properties of a novel phosphodiester analogue, nucleoside boranophosphorothioate

  摘要：

  我们合成了第一种硫代磷酸硼烷酯[(RO)2P(S)(BH3)-]磷酸二酯化合物的模拟物--二硫脒硫代磷酸硼烷酯；与天然核苷磷酸二酯[(RO)2P(O)(O)-]和硫代磷酸酯[(RO)2P(S)(O)-]相比，这种新的类似物更亲脂、更耐核酸酶。

  DOI：

  10.1039/a901157i
• 作为产物：
  描述：

  氯甲酸-9-芴基甲酯 、 beta-胸苷 在 吡啶 作用下， 反应 18.0h， 生成 5'-O-Fluorenylmethoxycarbonyl-thymidine
  参考文献：
  名称：

  寻找黄病毒抑制剂的第2部分：三甲基化，二苯基甲基化和其他烷基化的核苷类似物

  摘要：

  几种黄病毒，例如黄热病病毒和登革热病毒，会在人体内引起严重的致命感染。继我们最初的命中3'，5'-双歧化尿苷1之后，合成了一系列烷基化核苷类似物，并评估了它们对登革热病毒和黄热病病毒的体外抗病毒活性。迄今为止，烷基和芳基连接在糖环的各个位置，并带有杂环碱基的细微变化。在新的衍生物系列中，3'，5'- di- O-三苯甲基-5-氟-2'-脱氧尿苷（39）是该系列中最有效的衍生物，可抑制黄热病病毒和登革热病毒的复制，其50有效浓度百分比（EC 50）〜1μg/ mL，无明显细胞毒性。其他氟化衍生物被证明更具毒性。几乎所有具有3'，5'-二-O-苯甲酰基-2'-脱氧尿苷（50）的二苯基甲基化嘧啶核苷都具有很强的低至1μg/ mL的细胞毒性作用。

  DOI：

  10.1016/j.ejmech.2014.02.011

文献信息

• Allyl as internucleotide protecting group in DNA synthesis to be cleaved off by ammonia
  作者：Frank Bergmann、Erich Kueng、Patrick laiza、Willi Bannwarth

  DOI：10.1016/0040-4020(95)00344-8

  日期：1995.6

  Deprotection of allyl groups from internucleotide phosphotriester functions can be achieved not only with Pdo-mediated cleavage in the presence of an appropriate nucleophile but also under standard conditions for DNA fragments using conc. ammonia at elevated temperature. This observation widens the scope for chemical phosphorylation procedures based on phosphoramidite chemistry and creates possibilities

  烯丙基从核苷酸间磷酸三酯功能上的脱保护作用不仅可以在适当亲核试剂存在下用Pd o介导的裂解来实现，而且可以在标准条件下使用conc对DNA片段进行保护。氨在高温下。该发现扩大了基于亚磷酰胺化学的化学磷酸化程序的范围，并为无需修饰固相合成方法即可制备由DNA和肽组成的杂化分子提供了可能性。
• Solid-Phase Oligodeoxynucleotide Synthesis:  A Two-Step Cycle Using Peroxy Anion Deprotection
  作者：Agnieszka B. Sierzchala、Douglas J. Dellinger、Jason R. Betley、Tadeusz K. Wyrzykiewicz、Christina M. Yamada、Marvin H. Caruthers

  DOI：10.1021/ja030376n

  日期：2003.11.1

  phosphoramidite based oligodeoxynucleotide two-step synthesis method has been developed. Keys to this method are replacement of the 5'-dimethoxytrityl blocking group with an aryloxycarbonyl and the use of N-dimethoxytrityl protection for the exocyclic amines of adenine and cytosine. With these modifications, coupling of each 2'-deoxynucleoside 3'-phosphoramidite to the growing oligodeoxynucleotide

  开发了一种新型固相亚磷酰胺基寡脱氧核苷酸两步合成方法。该方法的关键是用芳氧基羰基替换 5'-二甲氧基三苯甲基封闭基团，并使用 N-二甲氧基三苯甲基保护腺嘌呤和胞嘧啶的环外胺。通过这些修饰，每个 2'-脱氧核苷 3'-亚磷酰胺与固体支持物上生长的寡脱氧核苷酸偶联后，可以用缓冲在 pH 9.6 的过氧阴离子的水性混合物处理。该试剂有效去除碳酸酯保护基团，同时氧化亚磷酸酯核苷酸间键。因此，新的两步合成循环是可能的。
• Compounds for protecting hydroxyls and methods for their use
  申请人：——

  公开号：US20020015961A1

  公开（公告）日：2002-02-07

  A hydrocarbyldithiomethyl-modified compound of the Formula: R 1 —O—CH 2 —S—S—R 2 or a salt thereof wherein R 1 is an organic molecule and R 2 is a hydrocarbyl is useful for protecting and/or blocking hydroxyl groups in organic molecules such as nucleotides. The hydrocarbyldithiomethyl-modified compounds can also be used for chemically synthesizing oligonucleotides and for sequencing nucleic acid compounds.

  一种Formula: R1-O-CH2-S-S-R2或其盐的羟烷基硫代甲基修饰化合物，其中R1是有机分子，R2是烃基，可用于保护和/或阻断核苷酸等有机分子中的羟基。这些羟烷基硫代甲基修饰化合物还可用于化学合成寡核苷酸和测序核酸化合物。
• Synthetic Approach to Stop-Codon Scanning Mutagenesis
  作者：Lihua Nie、Jason J. Lavinder、Mohosin Sarkar、Kimberly Stephany、Thomas J. Magliery

  DOI：10.1021/ja106894g

  日期：2011.4.27

  A general combinatorial mutagenesis strategy using common dimethoxytrityl-protected mononucleotide phosphoramidites and a single orthogonally protected trinucleotide phosphoramidite (Fmoc-TAG; Fmoc = 9-fluorenylmethoxycarbonyl) was developed to scan a gene with the TAG amber stop codon with complete synthetic control. In combination with stop-codon suppressors that insert natural (e.g., alanine) or unnatural (e.g., p-benzoylphenylalanine, Bpa) amino acids, a single DNA library can be used to incorporate different amino acids for diverse purposes. Here, we scanned TAG codons through part of the gene for a model four-helix bundle protein, Rop, which regulates the copy number of ColE1 plasmids. Alanine was incorporated into Rop for mapping its binding site using an in vivo activity screen, and subtle but important differences from in vitro gel-shift studies of Rop function are evident. As a test, Bpa was incorporated using a Phe14 amber mutant isolated from the scanning library. Surprisingly, Phel4Bpa-Rop is weakly active, despite the critical role of Phe14 in Rop activity. Bpa is a photoaffinity label unnatural amino acid that can form covalent bonds with adjacent molecules upon UV irradiation. Irradiation of Phe14Bpa-Rop, which is a dimer in solution like wildtype Rop, results in covalent dimers, trimers, and tetramers. This suggests that Phel4Bpa-Rop weakly associates as a tetramer in solution and highlights the use of Bpa cross-linking as a means of trapping weak and transient interactions.
• ——
  作者：Masatoshi Ushioda、Michinori Kadokura、Tomohisa Moriguchi、Akio Kobori、Morihiro Aoyagi、Kohji Seio、Mitsuo Sekine

  DOI：10.1002/1522-2675(200209)85:9<2930::aid-hlca2930>3.0.co;2-2

  日期：2002.9

  In connection with the synthesis of guanosine-capped of oligodeoxynucleotides on polymer supports, we found an unprecedented Si-O bond cleavage reaction, which occurred when polymer-linked oligodeoxynucleoticles having unprotected internucleotidic phosphate groups were allowed to react with the guanosine 5'-phosphorimidazolide derivative 18 in the presence of 4-nitro-6-(trifluoromethyl)-1H-benzotriazol-1-ol (Ntbt-OH) as an effective activator in pyridine. This side reaction was confirmed by the fact that the liquid-phase reaction of DMTrTpT-O-Si(iPr(2))OEt 42 with a simpler model compound. methyl phosphorimidazolide 34. in the presence of Ntbt-OH gave DMTrTpT 43. It turned out that the side reaction hardly occurs without unprotected internucleotidic phosphate groups on oligodeoxyriucleotides. The detailed study of this side reaction disclosed that Ntbt-OH directly attacks the Si-atom to release oligonucleotides from the resin. It is likely that Ntbt-OH serves as a very strong nucleophile in pyridine, especially to the Si-atom of the linker.