silylated thymine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: silylated thymine
• 英文别名: 5-methyl-3-trimethylsilyl-1H-pyrimidine-2,4-dione
• 化学式: C₈H₁₄N₂O₂Si
• 分子量: 198.297
• InChiKey: FDBIVKLXZNLRTG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.53
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  silylated thymine 、 benzoyloxymethyl ether 在 三氟甲磺酸三甲基硅酯 作用下， 以 二氯甲烷 为溶剂， 以14.5 g (50%)的产率得到1-<<(benzoyloxy)methyl>oxy>thymine
  参考文献：
  名称：

  Nucleoside analogs

  摘要：

  提供以下式的化合物：A磷酸甲氧甲氧甲氧基嘌呤/嘧啶衍生物，其化学式为##STR1##其中X和X'相同或不同，为氢或烷基。R和R'相同或不同，为氢、烷基、羟基烷基或烷酰基，B为嘌呤或嘧啶碱基。化学式为(VI)的化合物##STR2##其中X为卤素，Y为S-苯基、Se-苯基或卤素，B为咖啡碱、黄嘌呤、鸟嘌呤、8-溴鸟嘌呤、8-氯鸟嘌呤、8-甲基鸟嘌呤、8-硫鸟嘌呤、3-去氮鸟嘌呤、嘌呤、2-氨基嘌呤、2,6-二氨基嘌呤、腺嘌呤、3-去氮腺嘌呤、8-氨基鸟嘌呤、8-叠氮鸟嘌呤、8-羟基鸟嘌呤、胞嘧啶、5-乙基胞嘧啶、5-甲基胞嘧啶、胸腺嘧啶、尿嘧啶、5-氯尿嘧啶、5-溴尿嘧啶、5-乙基尿嘧啶、5-碘尿嘧啶、5-丙基尿嘧啶或5-乙烯基尿嘧啶、2-乙酰胺基-6-二苯基氨基嘌呤、6-N-二甲氨基甲基腺嘌呤或6-N-戊酰基腺嘌呤。化学式为(VII)的化合物##STR3##其中B为鸟嘌呤、8-鸟嘌呤、8-溴鸟嘌呤、8-氯鸟嘌呤、8-甲基鸟嘌呤、8-硫鸟嘌呤、3-去氮鸟嘌呤、8-氨基鸟嘌呤、8-叠氮鸟嘌呤、8-羟基鸟嘌呤、胞嘧啶、5-乙基胞嘧啶或5-甲基胞嘧啶。

  公开号：

  US05686611A1
• 作为产物：
  描述：

  胸腺嘧啶 在 (NH4)2 SO4 作用下， 生成 silylated thymine
  参考文献：
  名称：

  Process for the preparation of enantiomerically pure

  摘要：

  一种用于制备对映纯β-D-(-)-二氧兰核苷的不对称过程。对映纯的二氧兰核苷是活性HIV药剂，比之前制备的核苷的混合物更有效。这些化合物的抗病毒活性令人惊讶，因为通常被接受的理论认为内式构象中的基团，包括这些二氧兰，不是有效的抗病毒剂。对映纯的二氧兰核苷的毒性低于核苷混合物，因为不含非自然存在的α-异构体。该产品可用作研究工具，用于体外研究HIV的抑制，或可在制药组合物中给予，以抑制体内HIV的生长。

  公开号：

  US05179104A1
• 作为试剂：
  描述：

  Acetic acid (3aR,6R,6aS)-6-(tert-butyl-diphenyl-silanyloxymethyl)-2-methyl-hexahydro-furo[3,4-d]isoxazol-4-yl ester 在 silylated thymine 、 三氟甲磺酸三甲基硅酯 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 生成 1-[(3aR,4S,6R,6aS)-6-(tert-Butyl-diphenyl-silanyloxymethyl)-2-methyl-hexahydro-furo[3,4-d]isoxazol-4-yl]-5-methyl-1H-pyrimidine-2,4-dione 、 1-[(3aR,4R,6R,6aS)-6-(tert-Butyl-diphenyl-silanyloxymethyl)-2-methyl-hexahydro-furo[3,4-d]isoxazol-4-yl]-5-methyl-1H-pyrimidine-2,4-dione
  参考文献：
  名称：

  Synthesis of [3.3.0] bicyclic isoxazolidinyl nucleosides

  摘要：

  The isoxazolidine derivative 6, prepared from an intermolecular 1,3-dipolar cycloaddition of the (5S)-unsaturated lactone 5 and N-methylnitrone, was effectively used for the synthesis of [3.3.0] bicyclic isoxazolidinyl cytidine 4a and thymidine 4b. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/s0960-894x(96)00262-4

文献信息

• Process for the preparation of enantiomerically pure
  申请人：University of Georgia Research Foundation, Inc.

  公开号：US05179104A1

  公开（公告）日：1993-01-12

  An asymmetric process for the preparation of enantiomerically pure .beta.-D-(-)-dioxolane-nucleosides. The enantiomerically pure dioxolane nucleosides are active HIV agents, that are significantly more effective than the prior prepared racemic mixtures of the nucleosides. The anti-viral activity of the compounds is surprising in light of the generally accepted theory that moieties in the endo conformation, including these dioxolanes, are not effective antiviral agents. The toxicity of the enantiomerically pure dioxolane nucleosides is lower that that of the racemic mixture of the nucleosides, because the nonnaturally occurring .alpha.-isomer is not included. The product can be used as a research tool to study the inhibition of HIV in vitro or can be administered in a pharmaceutical composition to inhibit the growth of HIV in vivo.

  一种用于制备对映纯β-D-(-)-二氧兰核苷的不对称过程。对映纯的二氧兰核苷是活性HIV药剂，比之前制备的核苷的混合物更有效。这些化合物的抗病毒活性令人惊讶，因为通常被接受的理论认为内式构象中的基团，包括这些二氧兰，不是有效的抗病毒剂。对映纯的二氧兰核苷的毒性低于核苷混合物，因为不含非自然存在的α-异构体。该产品可用作研究工具，用于体外研究HIV的抑制，或可在制药组合物中给予，以抑制体内HIV的生长。
• Process for the preparation of 2'-halo-beta-L-arabinofuranosyl nucleosides
  申请人：——

  公开号：US20030060622A1

  公开（公告）日：2003-03-27

  The present invention is directed to the process for the preparation of 2′-deoxy-2′-halo-&bgr;-L-arabinofuranosyl nucleosides, and in particular, 2′-deoxy-2′-fluoro-&bgr;-L-arabinofuranosyl thymine (L-FMAU), from L-arabinose, which is commercially available and less expensive than L-ribose or L-xylose, in ten steps. All of the reagents and starting materials are inexpensive and no special equipment is required to carry out the reactions.

  本发明涉及制备2'-脱氧-2'-卤代-β-L-阿拉伯呋喃核苷的过程，特别是从商业可获得且价格较低的L-阿拉伯糖制备2'-脱氧-2'-氟-β-L-阿拉伯呋喃胸苷（L-FMAU），共经过十个步骤。所有试剂和起始原料都廉价，并且不需要特殊设备来进行反应。
• Methods of manufacture of 2'-deoxy-beta-L-nucleosides
  申请人：——

  公开号：US20040266996A1

  公开（公告）日：2004-12-30

  The present invention relates to the synthesis of 2′-deoxy-&bgr;-L-thymidine, 2′-deoxy-&bgr;-L-uridine and 2′-deoxy-&bgr;-L-cytidine, and their derivatives, such as the 3′-O-acyl or 3′,5′-O-diacyl prodrugs, including the 3′-O-L-aminoacyl and 3′,5′-O-L-diaminoacyl prodrugs, and particularly the 3′-O-L-valinyl and 3′,5′-O-L-divalinyl prodrugs.

  本发明涉及2'-脱氧-β-L-胸苷、2'-脱氧-β-L-尿苷和2'-脱氧-β-L-胞苷的合成，以及它们的衍生物，如3'-O-酰基或3',5'-O-二酰基前药，包括3'-O-L-氨基酰和3',5'-O-L-二氨基酰前药，特别是3'-O-L-缬氨酰和3',5'-O-L-二缬氨酰前药。
• EP1533294
  申请人：——

  公开号：——

  公开（公告）日：——
• Design, synthesis and inhibitory activity against Mycobacterium tuberculosis thymidine monophosphate kinase of acyclic nucleoside analogues with a distal imidazoquinolinone
  作者：Olga Familiar、Hélène Munier-Lehmann、José Antonio Aínsa、María-José Camarasa、María-Jesús Pérez-Pérez

  DOI：10.1016/j.ejmech.2010.09.056

  日期：2010.12

  Thymidine monophosphate kinase from Mycobacterium tuberculosis (TMPKmt) has been proposed as an attractive target in the search of new agents to fight against tuberculosis. We recently reported that thymine derivatives carrying a naphtholactam or naphthosultam moiety at position 4 of a (Z)-butenyl chain inhibit TMPKmt in the sub mu M range. Here we describe the replacement of the planar naphtholactam and naphthosultam rings in our identified hits by 5,6-dihydro-1H-imidazo[4,5,1-ij]quinolinones and a 5,6-dihydro-1H,4H-1,2,5-thiadiazolo[4,3,2-ij]quinoline-2,2-dioxide where the planarity has been broken. Interestingly, these non-planar compounds were similarly potent against the target enzyme than their aromatic analogues, suggesting a bioisosteric behavior that may also be applied to other biologically active compounds. The synthesis of the different targeted imidazoquinolinones has been successfully performed via a hypervalent iodide mediated oxidative cyclization of N-methoxyureas catalized by bis(trifluoroacetoxy)iodobenzene (PIFA) expanding the reported use of this reagent for the synthesis of differently substituted imidazoquinolinones. (C) 2010 Elsevier Masson SAS. All rights reserved.