1-(3'-Iodopropyl)-4-methyl-2,6,7-trioxabicyclo<2,2,2>octane | 74900-28-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(3'-Iodopropyl)-4-methyl-2,6,7-trioxabicyclo<2,2,2>octane
• 英文别名: 1-(3-iodopropyl)-4-methyl-2,6,7-trioxa-bicyclo[2.2.2]octane；1-(3-iodopropyl)-4-methyl-2,6,7-trioxabicyclo[2.2.2]octane
• CAS: 74900-28-0
• 化学式: C₉H₁₅IO₃
• 分子量: 298.121
• InChiKey: MBNCIJURMLVSIZ-UHFFFAOYSA-N

物化性质

• 沸点：
  284.8±20.0 °C(Predicted)
• 密度：
  1.670±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  27.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(3'-Iodopropyl)-4-methyl-2,6,7-trioxabicyclo<2,2,2>octane 在 锂硼氢 、 caesium carbonate 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 32.0h， 生成
  参考文献：
  名称：

  Design, synthesis, cytocidal activity and estrogen receptor α affinity of doxorubicin conjugates at 16α-position of estrogen for site-specific treatment of estrogen receptor positive breast cancer

  摘要：

  Doxorubicin (DOX) is an important medicine for the treatment of breast cancer, which is the most frequently diagnosed and the most lethal cancer in women worldwide. However, the clinical use of DOX is impeded by serious toxic effects such as cardiomyopathy and congestive heart failure. Covalently linking DOX to estrogen to selectively deliver the drug to estrogen receptor-positive (Er) cancer tissues is one of the strategies under investigation for improving the efficacy and decreasing the cardiac toxicity of DOX. However, conjugation of drug performed until now was at 3- or 17-position of estrogen, which is not ideal since the hydroxyl groups at this position are important for receptor binding affinity. In this study, we designed, prepared and evaluated in vitro the first estrogen-doxorubicin conjugates at 16 alpha-position of estradiol termed E-DOXs (8a-d). DOX was conjugated using a 3-9 carbon atoms alkylamide linking arm. E-DOXs were prepared from estrone using a seven-step procedure to afford the desired conjugates in low to moderate yields. The antiproliferative activities of the E-DOX 8a conjugate through a 3-carbon spacer chain on ER+ MCF7 and HT-29 are in the micromolar range while inactive on M21 and the ER- MDA-MB-231 cells (>50 mu M). Compound 8a exhibits a selectivity ratio (ER+/ER- cell lines) of >3.5. Compounds 8b-8d bearing alkylamide linking arms ranging from 5 to 9 carbon atoms were inactive at the concentrations tested (>50 mu M). Interestingly, compounds 8a-8c exhibited affinity for the estrogen receptor alpha (ER alpha) in the nanomolar range (72-100 nM) whereas compound 8d exhibited no affinity at concentrations up to 215 nM. These results indicate that a short alkylamide spacer is required to maintain both antiproliferative activity toward ER+ MCF7 and affinity for the ER alpha of the E-DOX conjugates. Compound 8a is potentially a promising conjugate to target ER. breast cancer and might be useful also for the design of more potent E-DOX conjugates. (C) 2012 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2012.06.004
• 作为产物：
  描述：

  1,1,1-三(羟甲基)乙烷 在 碳酸氢钠 、 sodium iodide 作用下， 以 丙酮 、 苯 为溶剂， 生成 1-(3'-Iodopropyl)-4-methyl-2,6,7-trioxabicyclo<2,2,2>octane
  参考文献：
  名称：

  将羧基掩盖为2,6,7-三恶双环[2.2.2]辛烷：在合成含酯和羧基的烷基钴肟中的应用

  摘要：

  2,6,7-三氧杂双环-[2.2.2]辛烷对酸的水解稳定性介于1,1,1-三乙氧基乙烷和1-甲基-2,8,9-三氧杂-金刚烷之间。描述了该三氧杂双环辛烷基作为掩蔽的羧基官能团的合成应用。

  DOI：

  10.1039/c39800000207

文献信息

• Design, Synthesis, and Validation of a Branched Flexible Linker for Bioactive Peptides
  作者：Martina E. Bowen、Yasunari Monguchi、Rajesh Sankaranarayanan、Josef Vagner、Lucinda J. Begay、Liping Xu、Bhumasamudram Jagadish、Victor J. Hruby、Robert J. Gillies、Eugene A. Mash

  DOI：10.1021/jo062276g

  日期：2007.3.1

  A branched flexible linker that incorporates a fluorescent dansyl moiety was synthesized and used to connect two high affinity NDP-α-MSH ligands or two low affinity MSH(4) ligands. The linker was incorporated into the conjugate by solid-phase synthesis. In vitro biological evaluations showed that potency of binding to the human melanocortin 4 receptor was not diminished for linker−ligand combinations

  合成了一个分支的柔性接头，其中掺入了荧光丹磺酰基部分，并用于连接两个高亲和力的NDP-α-MSH配体或两个低亲和力的MSH（4）配体。通过固相合成将接头引入到缀合物中。体外生物学评估显示，相对于单独的相应配体，对于接头-配体组合，与人黑皮质素4受体结合的效力并未降低。
• A short,three-component total synthesis of 12-hydroxyeicosa-5,8,14(Z), 10(E)-tetraenoic acid (12-HETE) via the corresponding ketone
  作者：E.J. Corey、Keith Kyler、Natarajan Raju

  DOI：10.1016/s0040-4039(01)81538-0

  日期：1984.1

  A highly effective synthesis of (±)-12-HETE (1) from the components 2, 3 and 6 is described which employs a new class of cuprate reagents.

  描述了由组分2、3和6高效合成（±）-12-HETE（1）的方法，该方法使用了新型的铜酸盐试剂。
• Development of imidazole alkanoic acids as mGAT3 selective GABA uptake inhibitors
  作者：Silke Hack、Babette Wörlein、Georg Höfner、Jörg Pabel、Klaus T. Wanner

  DOI：10.1016/j.ejmech.2011.01.042

  日期：2011.5

  inhibitors starting from of 1H-imidazol-4-ylacetic acid with the carboxylic acid side chain originating from different positions and varying in length have been synthesized and tested for the inhibitory potency at the four GABA uptake transporters mGAT1–4 stably expressed in HEK cells. Further two bicyclic compounds with a rigidified carboxylic acid side chain were included in this study. The results of the

  合成了一系列新的潜在的GABA吸收抑制剂，这些抑制剂从1 H-咪唑-4-基乙酸开始，羧酸侧链来自不同的位置，且长度不同，并在四个GABA吸收转运蛋白mGAT1上测试了其抑制能力。 –4在HEK细胞中稳定表达。这项研究还包括了另外两个带有刚性羧酸侧链的双环化合物。生物学测试的结果表明，大多数ω-咪唑链烷酸和链烯酸衍生物作为mGAT3的GABA吸收抑制剂表现出最高的效力。
• Carbocyclic ring expansion reactions via radical chain processes. Part II.
  作者：Jack E. Baldwin、Robert M. Adlington、Jeremy Robertson

  DOI：10.1016/s0040-4020(01)82331-0

  日期：1991.8

  The further exploitation of the homolytic ring expansion reaction of cyclohexanone derivatives is described. The application of this methodology to the preparation of exomethylene cycloalkanones, α-alkylated cyclodecanones, indanones, and decalinols is described.

  描述了环己酮衍生物的均相扩环反应的进一步开发。描述了该方法在制备环己烯基环烷酮，α-烷基化环癸烷酮，茚满酮和十氢萘酚中的应用。
• Functionalization of C60 via organometallic reagents
  作者：Elise Champeil、Conor Crean、Carlos Larraya、Gennaro Pescitelli、Gloria Proni、Léon Ghosez

  DOI：10.1016/j.tet.2008.08.017

  日期：2008.11

  reacted with alanine ethyl ester under standard peptide coupling conditions to give 14 in 55% yield. Attempts to generate a silyl enol ether from the reaction of aldehyde 10b with TIPSOTf and triethylamine failed. Instead the reaction led to a cyclized ether 16a (or alcohol 16b in the absence of silylating agent) resulting from the addition of an initially formed fulleride anion to the aldehyde group. The

  的反应[60]富勒烯与携带原酸酯，缩醛或其他端基得到的加合物的有机锂和格氏试剂3 - 5用三氟乙酸淬火后在6-6键C60的。在叔丁醇钾的存在下，加合物可以很容易地用甲基碘或苄基溴甲基化或苄基化，从而仅生成1,4-二取代的C60 6和7a，b。原酸酯，缩醛和甲硅烷基醚基团的裂解得到相应的羧酸9，醛10a，b和11以及醇12和13a，b。在标准肽偶联条件下，羧酸9容易与丙氨酸乙酯反应，以55％的收率得到14。尝试从醛10b与TIPSOTf和三乙胺的反应生成甲硅烷基烯醇醚失败。取而代之的是，该反应产生了环化的醚16a（或在不存在甲硅烷基化剂的情况下为醇16b），这是由于向醛基中添加了最初形成的富勒阴离子而产生的。相应的乙缩醛4b反应相似。醛10b与苯胺的反应也得到环化产物19。令人惊讶的是，醛11不再带有酸性富勒烯质子与苯胺反应，生成的产物20是分子内Diels-Alder反应，然后是主要形成的