3'-O-lauroyl-β-thymidine | 146961-93-5

• 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: 3'-O-lauroyl-β-thymidine
• 英文别名: 3'-O-dodecanoylthymidine；[(2R,3S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl] dodecanoate
• CAS: 146961-93-5
• 化学式: C₂₂H₃₆N₂O₆
• 分子量: 424.538
• InChiKey: NPXFFHDAWNZXOK-IPMKNSEASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  30
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3'-O-lauroyl-β-thymidine 在 盐酸 、 sodium methylate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 52.17h， 生成 1-[(2R,4S,5R)-5-[[(2R,3S,5R)-2-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]sulfanylmethoxymethyl]-4-hydroxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione
  参考文献：
  名称：

  Synthesis and binding properties of pyrimidine oligodeoxynucleoside analogs containing neutral phosphodiester replacements: the formacetal and 3'-thioformacetal internucleoside linkages

  摘要：

  The replacement of the phosphodiester linkage with neutral, achiral, nuclease resistant entities is desirable for the development of oligodeoxynucleotide (ODN) analogs as therapeutic agents in either the antisense or antigene modes. Described herein is the use of the formacetal and 3'-thioformacetal connections as phosphodiester backbone analogs. Pyrimidine dimer blocks containing these moieties were synthesized and incorporated into ODNs in an alternating array with phosphodiester bonds, such that the ODNs had seven acetal and seven phosphodiester linkages. The binding properties of the resulting chimeric ODNs to single-stranded (ss) RNA and double-stranded (ds) DNA were then determined. ssRNA binding properties were determined by thermal denaturation (Tm) analysis, and the 3'-thioformacetal ODN/ssRNA duplex showed a 5.5-degrees-C enhancement in Tm relative to the control phosphodiester ODN. The triple helix formation properties of the 3'-thioformacetal and formacetal ODNs were determined by footprint and restriction enzyme inhibition assays. The 3'-thioformacetal ODN binds to dsDNA with an affinity slightly less than the control ODN. The high affinity and specificity of an ODN containing the 3'-thioformacetal for the ssRNA target and dsDNA target suggest that this linkage is a promising analog for both antisense and triple helix therapeutic applications.

  DOI：

  10.1021/jo00063a014
• 作为产物：
  描述：

  保护胸苷 在 吡啶 、 对甲苯磺酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 18.5h， 生成 3'-O-lauroyl-β-thymidine
  参考文献：
  名称：

  Synthesis and binding properties of pyrimidine oligodeoxynucleoside analogs containing neutral phosphodiester replacements: the formacetal and 3'-thioformacetal internucleoside linkages

  摘要：

  The replacement of the phosphodiester linkage with neutral, achiral, nuclease resistant entities is desirable for the development of oligodeoxynucleotide (ODN) analogs as therapeutic agents in either the antisense or antigene modes. Described herein is the use of the formacetal and 3'-thioformacetal connections as phosphodiester backbone analogs. Pyrimidine dimer blocks containing these moieties were synthesized and incorporated into ODNs in an alternating array with phosphodiester bonds, such that the ODNs had seven acetal and seven phosphodiester linkages. The binding properties of the resulting chimeric ODNs to single-stranded (ss) RNA and double-stranded (ds) DNA were then determined. ssRNA binding properties were determined by thermal denaturation (Tm) analysis, and the 3'-thioformacetal ODN/ssRNA duplex showed a 5.5-degrees-C enhancement in Tm relative to the control phosphodiester ODN. The triple helix formation properties of the 3'-thioformacetal and formacetal ODNs were determined by footprint and restriction enzyme inhibition assays. The 3'-thioformacetal ODN binds to dsDNA with an affinity slightly less than the control ODN. The high affinity and specificity of an ODN containing the 3'-thioformacetal for the ssRNA target and dsDNA target suggest that this linkage is a promising analog for both antisense and triple helix therapeutic applications.

  DOI：

  10.1021/jo00063a014

文献信息

• Regioselective Acylation of Nucleosides Catalyzed by<i>Candida Antarctica</i>Lipase B: Enzyme Substrate Recognition
  作者：Ning Li、Min-Hua Zong、Ding Ma

  DOI：10.1002/ejoc.200800780

  日期：2008.11

  The substrate recognition of Candida antarctica lipase B (CAL-B) in the acylation of nucleosides was revealed through rational substrate engineering for the first time. CAL-B displayed lower activities and excellent 5-regioselectivities (94 to 99 %) in the acylation of ribonucleosides 1f–1j as compared to those in the acylation of 2-deoxynucleosides 1a– 1e. The excellent regioselectivities might be

  首次通过合理的底物工程揭示了南极念珠菌脂肪酶B（CAL-B）在核苷酰化中的底物识别。与 2-脱氧核苷 1a-1e 的酰化相比，CAL-B 在核糖核苷 1f-1j 的酰化中表现出较低的活性和优异的 5-区域选择性（94% 至 99%）。优异的区域选择性可能归因于存在于 2-羟基中的有利的空间位阻
• Regioselective acylation of nucleosides and their analogs catalyzed by Pseudomonas cepacia lipase: enzyme substrate recognition
  作者：Ning Li、Min-Hua Zong、Ding Ma

  DOI：10.1016/j.tet.2008.11.045

  日期：2009.1

  The substrate recognition of Pseudomonas cepacia lipase in the acylation of nucleosides was investigated by means of rational substrate engineering for the first time. P. cepacia lipase displayed excellent 3′-regioselectivities (96 to >99%) in the lauroylation of 2′-deoxynucleosides 1a–1e, while low to good 3′-regioselectivities (59–89%) in the lauroylation of ribonucleosides 1f–1j. It might be due

  首次通过合理的底物工程研究了假单胞菌脂肪酶在核苷酰化中的底物识别。P. cepacia脂肪酶在2'-脱氧核苷1a - 1e的月桂酰化中显示出极好的3'-区域选择性（96至> 99％），而在核糖核苷1f -12的月桂酰化中显示低至良好的3'-区域选择性（59-89％）。1J。这可能是由于1f – 1j的2'-羟基之间不利的氢键相互作用酪氨酸残基中的酪氨酸残基和酚羟基存在于酶的另一个疏水口袋中，可稳定5'-酰化过渡态的构象，从而增加次要区域异构体的数量。此外，脂肪酶成功地合成了氟尿苷的各种酯衍生物，其转化率高（99％），并且在温和条件下具有良好至优异的3'-区域选择性。检查了酶对各种酰基供体的识别。根据脂肪酶活性位点的结构，尤其是大小，形状和理化性质，对酰基的酶促识别是合理的。