N-Fmoc-(3R,4R)-4-(hydroxymethyl)pyrrolidin-3-ol | 362600-15-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: N-Fmoc-(3R,4R)-4-(hydroxymethyl)pyrrolidin-3-ol
• 英文别名: 9H-fluoren-9-ylmethyl (3R,4R)-3-hydroxy-4-(hydroxymethyl)pyrrolidine-1-carboxylate
• CAS: 362600-15-5
• 化学式: C₂₀H₂₁NO₄
• 分子量: 339.391
• InChiKey: YUVRKZQWMQJWDF-YJYMSZOUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  70
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-Fmoc-(3R,4R)-4-(hydroxymethyl)pyrrolidin-3-ol 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 15.0h， 以95%的产率得到(3R,4R)-3-hydroxy-4-(hydroxymethyl)pyrrolidine
  参考文献：
  名称：

  2-脱氧-D-呋喃核糖的氮杂类似物的合成及其同系物。

  摘要：

  一锅反应中的氮杂糖是通过醛糖中氨基前体的催化还原反应，然后进行分子内还原性氨基烷基化反应而获得的。（3R，4S）-4-[（1S）-1,2-二羟乙基]吡咯烷-3-醇是通过两种不同的策略通过3-C-氰基-3-脱氧-D-核糖-戊呋喃糖从D-木糖获得的或3-C-叠氮基甲基3-脱氧-D-核糖-戊呋喃糖，总收率分别为6％和16％。在相应的Fmoc-氮杂糖中二醇基团的氧化裂解，然后脱保护，得到（3R，4R）-4-（羟甲基）吡咯烷丁-3-醇。（3R，4S）-4-[（1S，2R）-1,2,3-三羟丙基]吡咯烷-3-醇是由双丙酮-D-葡萄糖通过3-脱氧-3-C-硝基甲基-D-阿洛糖合成的总产率为7％。

  DOI：

  10.1016/s0008-6215(01)00132-x
• 作为产物：
  描述：

  (+/-)-trans-ethyl 1-benzyl-4-hydroxy-5-oxopyrrolidine-3-carboxylate 在 dimethyl sulfide borane 、 碳酸氢钠 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 丙酮 为溶剂， 反应 27.0h， 生成 N-Fmoc-(3R,4R)-4-(hydroxymethyl)pyrrolidin-3-ol
  参考文献：
  名称：

  Profiling base excision repair glycosylases with synthesized transition state analogs

  摘要：

  Two base excision repair glycosylase (BER) transition state (TS) mimics, (3R,4R)-1-benzyl (hydroxymethyl) pyrrolidin-3-ol (1NBn) and (3R,4R)-(hydroxymethyl) pyrrolidin-3-ol (1N), were synthesized using an improved method. Several BER glycosylases that repair oxidized DNA bases, bacterial formamidopyrimdine glycosylase (Fpg), human OG glycosylase (hOGG1) and human Nei-like glycosylase 1 (hNEIL1) exhibit exceptionally high affinity (K-d similar to pM) with DNA duplexes containing the 1NBn and 1N nucleotide. Notably, comparison of the K-d values of both TS mimics relative to an abasic analog (THF) in duplex contexts paired opposite C or A suggest that these DNA repair enzymes use distinctly different mechanisms for damaged base recognition and catalysis despite having overlapping substrate specificities. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.085

文献信息

• OLIGONUCLEOTIDES COMPRISING A NON-PHOSPHATE BACKBONE LINKAGE
  申请人：MANOHARAN MUTHIAH

  公开号：US20090281299A1

  公开（公告）日：2009-11-12

  One aspect of the present invention relates to a ribonucleoside substituted with a phosphonamidite group at the 3′-position. In certain embodiments, the phosphonamidite is an alkyl phosphonamidite. Another aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one non-phosphate linkage. Representative non-phosphate linkages include phosphonate, hydroxylamine, hydroxylhydrazinyl, amide, and carbamate linkages. In certain embodiments, the non-phosphate linkage is a phosphonate linkage. In certain embodiments, a non-phosphate linkage occurs in only one strand. In certain embodiments, a non-phosphate linkage occurs in both strands. In certain embodiments, a ligand is bound to one of the oligonucleotide strands comprising the double-stranded oligonucleotide. In certain embodiments, a ligand is bound to both of the oligonucleotide strands comprising the double-stranded oligonucleotide. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one non-phosphate linkage. Representative non-phosphate linkages include phosphonate, hydroxylamine, hydroxylhydrazinyl, amide, and carbamate linkages. In certain embodiments, the non-phosphate linkage is a phosphonate linkage. In certain embodiments, a ligand is bound to the oligonucleotide strand. In certain embodiments, the oligonucleotide comprises at least one modified sugar moiety.

  本发明的一个方面涉及到一种在3'-位点上用磷酰胺基取代的核糖核苷。在某些实施例中，磷酰胺基是一种烷基磷酰胺基。本发明的另一个方面涉及到至少含有一种非磷酸酯连接的双链寡核苷酸。代表性的非磷酸酯连接包括磷酸酯、羟胺、羟基肼、酰胺和氨基甲酸酯连接。在某些实施例中，非磷酸酯连接是磷酸酯连接。在某些实施例中，非磷酸酯连接仅出现在一个链上。在某些实施例中，非磷酸酯连接出现在两个链上。在某些实施例中，配体与包含双链寡核苷酸的寡核苷酸链的其中一个链结合。在某些实施例中，配体与包含双链寡核苷酸的寡核苷酸链的两个链都结合。在某些实施例中，寡核苷酸链包括至少一个修饰的糖基团。本发明的另一个方面涉及到至少含有一种非磷酸酯连接的单链寡核苷酸。代表性的非磷酸酯连接包括磷酸酯、羟胺、羟基肼、酰胺和氨基甲酸酯连接。在某些实施例中，非磷酸酯连接是磷酸酯连接。在某些实施例中，配体与寡核苷酸链结合。在某些实施例中，寡核苷酸包括至少一个修饰的糖基团。
• SINGLE-STRANDED AND DOUBLE-STRANDED OLIGONUCLEOTIDES COMPRISING A 2-ARYLPROPYL MOIETY
  申请人：MANOHARAN Muthiah

  公开号：US20100197899A1

  公开（公告）日：2010-08-05

  The present invention provides single-stranded and double-stranded oligonucleotides comprising at least one aralkyl ligand that improvise the pharmacokinetic properties of the oligonucleotide. The aralkyl ligands of the present invention include naproxen, ibuprofen, and derivatives thereof. The present invention also provides method for modulating gene expression using the modified oligonucleotide compounds and compositions comprising those modified oligonucleotides.

  本发明提供了含有至少一个芳基烷基配体的单链和双链寡核苷酸，该配体可改善寡核苷酸的药代动力学特性。本发明的芳基烷基配体包括萘普生、布洛芬及其衍生物。本发明还提供了使用修饰的寡核苷酸化合物调节基因表达的方法和包含这些修饰的寡核苷酸的组合物。
• Synthesis of 1′-aza-C-nucleosides from (3R,4R)-4-(hydroxymethyl)pyrrolidin-3-ol
  作者：Vyacheslav V Filichev、Erik B Pedersen

  DOI：10.1016/s0040-4020(01)00920-6

  日期：2001.10

  Pyrimidine 1'-aza-C-nucleosides are synthesised by the fusion of 5-bromouracil, 5-bromocytosine and 5-bromoisocytosine with (3R,4R)-4-(hydroxymethyl)pyrrolidin-3-ol in 40-41% yield. A homologue of 1'-aza-Psi -uridine is obtained in a Mannich reaction in 65% yield by treatment of the azasugar, paraformaldehyde and uracil. N-Alkylation of (3R,4R)-4-(hydroxymethyl)pyrrolidin-3-ol with 6-chloromethyluracil gives the 6-regioisomeric homologue. (3R,4R)-4-(Hydroxymethyl)pyrrolidin-3-ol is synthesised in 25% overall yield from diacetone-D-glucose via 3-C-(azidomethyl)-3-deoxy-D-allose which is subjected to an intramolecular reductive amino alkylation reaction to give (3R,4S)-4-[(1S,2R)-1,2,3-trihydroxypropyl]pyrrolidin-3-ol followed by Fmoc protection, oxidative cleavage of the triol group with further reduction of the obtained aldehyde and subsequent deprotection of the nitrogen atom. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Protected monomers
  申请人：Manoharan Muthiah

  公开号：US20070179100A1

  公开（公告）日：2007-08-02

  This invention relates to protected monomers for the synthesis of iRNA agents.
• US7615618B2
  申请人：——

  公开号：US7615618B2

  公开（公告）日：2009-11-10