1-acetoxy-1'-(1,3-dioxan-2-yl)ferrocene | 1241848-96-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 1-acetoxy-1'-(1,3-dioxan-2-yl)ferrocene
• 英文别名: 1-(1,3-dioxan-2-yl)-1'-iodoferrocene；cyclopenta-1,3-dien-1-yl acetate;2-cyclopenta-2,4-dien-1-yl-1,3-dioxane;iron(2+)
• CAS: 1241848-96-3
• 化学式: C₁₆H₁₈FeO₄
• 分子量: 330.164
• InChiKey: YWPGJOCZQNCRLQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.17
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-bromo-6-deoxy-1,2;3,5-(diisopropylidene)-α-D-glucofuranose 、 1-acetoxy-1'-(1,3-dioxan-2-yl)ferrocene 在 sodium methylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以59%的产率得到1-[3-(7-chloroquinolin-4-ylamino)ethylamino]-1'-[6-(1,2;3,5-diisopropylidene)-α-D-glucofuranosidyl]ferrocene
  参考文献：
  名称：

  1,1′-Disubstituted Ferrocenyl Carbohydrate Chloroquine Conjugates as Potential Antimalarials

  摘要：

  This work presents a new class of organometallic antimalarials, based on a ferrocene scaffold, bearing a chloroquine derivative and a 1,2;3,5-(diisopropylidene)-alpha-D-glucofuranose moiety in a 1,1'-heteroannular substitution pattern. Synthesis proceeds via orthogonal functionalization of ferrocene, giving 1-acetoxy-1'-(1,3-dioxan-2-yl)ferrocene (15) as the precursor for modular introduction of the carbohydrate (16, 17) followed by subsequent reductive amination with chloroquine building blocks 8-10, yielding the 1-[3-(7-chloroquinolin-4-ylamino)alkylamino]-1'-[6-(1,2;3,5-diisopropylidene)-alpha-D-glucofuranosidyl]ferrocenes 18-20. After complete characterization of these new, trifunctional conjugates, they were examined for their antiplasmodial activity in a chloroquine-susceptible strain of Plasmodium falciparum (D10) and in two chloroquine-resistant strains (Dd2 and K1). Their activity was compared to that of the monosubstituted reference conjugates 1-3 and the 1,2-disubstituted regioisomers 4-6. Compounds 19 and 20 exhibited consistently high activity in in vitro antiplasmodial activity assays performed in Dd2 and K1 strains, performing better than the reference compounds chloroquine and the monosubstituted and 1,2-disubstituted compounds 1-6.

  DOI：

  10.1021/om300354x
• 作为产物：
  描述：

  1-(1,3-dioxan-2-yl)-1'-iodoferrocene 、 溶剂黄146 在 copper(I) oxide 作用下， 以 乙腈 为溶剂， 反应 0.5h， 以85%的产率得到1-acetoxy-1'-(1,3-dioxan-2-yl)ferrocene
  参考文献：
  名称：

  1,1′-Disubstituted Ferrocenyl Carbohydrate Chloroquine Conjugates as Potential Antimalarials

  摘要：

  This work presents a new class of organometallic antimalarials, based on a ferrocene scaffold, bearing a chloroquine derivative and a 1,2;3,5-(diisopropylidene)-alpha-D-glucofuranose moiety in a 1,1'-heteroannular substitution pattern. Synthesis proceeds via orthogonal functionalization of ferrocene, giving 1-acetoxy-1'-(1,3-dioxan-2-yl)ferrocene (15) as the precursor for modular introduction of the carbohydrate (16, 17) followed by subsequent reductive amination with chloroquine building blocks 8-10, yielding the 1-[3-(7-chloroquinolin-4-ylamino)alkylamino]-1'-[6-(1,2;3,5-diisopropylidene)-alpha-D-glucofuranosidyl]ferrocenes 18-20. After complete characterization of these new, trifunctional conjugates, they were examined for their antiplasmodial activity in a chloroquine-susceptible strain of Plasmodium falciparum (D10) and in two chloroquine-resistant strains (Dd2 and K1). Their activity was compared to that of the monosubstituted reference conjugates 1-3 and the 1,2-disubstituted regioisomers 4-6. Compounds 19 and 20 exhibited consistently high activity in in vitro antiplasmodial activity assays performed in Dd2 and K1 strains, performing better than the reference compounds chloroquine and the monosubstituted and 1,2-disubstituted compounds 1-6.

  DOI：

  10.1021/om300354x

文献信息

• Modular Synthesis of 1,2- and 1,1′-Disubstituted Ferrocenyl Carbohydrate Chloroquine and Mefloquine Conjugates as Potential Antimalarial Agents
  作者：Christoph Herrmann、Paloma F. Salas、Brian O. Patrick、Carmen de Kock、Peter J. Smith、Michael J. Adam、Chris Orvig

  DOI：10.1021/om300392q

  日期：2012.8.27

  The modular synthesis of novel organometallic antimalarials based on a 1,2- or 1,1′-disubstituted ferrocene scaffold (10 and 11) is presented. Ferrocenes were substituted via an ether linker with either 7-chloroquinoline or 2,8-bis(trifluoromethyl)quinoline, as a chloroquine or mefloquine derivative, respectively. Diisopropylidene-protected 6-amino-6-deoxyglucofuranose (18) or 6-amino-6-deoxygalactopyranose

  提出了基于1,2-或1,1'-二取代的二茂铁支架（10和11）的新型有机金属抗疟药的模块化合成。二茂铁经醚接头分别用7-氯喹啉或2,8-双（三氟甲基）喹啉取代，分别为氯喹或甲氟喹衍生物。二异亚丙基保护的6-氨基-6- deoxyglucofuranose（18）或6-氨基-6- deoxygalactopyranose（21）通过还原性胺化偶联，得到目标共轭物24 - 27和30。使用微波反应器代替常规加热可以显着提高产率，这也缩短了反应时间。完全表征后，检查这些新型三功能偶联物在恶性疟原虫（D10）的氯喹敏感性（CQS）菌株和耐氯喹（CQR）菌株（Dd2）中的抗疟原虫活性。所确定的IC 50值在低微摩尔范围内。碳水化合物的引入导致活性增加（> 200μM（16，D10）至1.2μM（24，D10））。在Dd2中测得的最佳活性为26（IC 50= 0.77μM）。阻力指数（RI）为所有测量