(6S,7R,8R,8aS)-8a-(hydroxymethyl)-octahydroindolizine-6,7,8-triol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚里西啶
• 英文名称: (6S,7R,8R,8aS)-8a-(hydroxymethyl)-octahydroindolizine-6,7,8-triol
• 英文别名: 8a(S)-hydroxymethyl-1-deoxycastanospermine-3-one；(6S,7R,8R,8aS)-8a-(hydroxymethyl)-2,3,5,6,7,8-hexahydro-1H-indolizine-6,7,8-triol
• 化学式: C₉H₁₇NO₄
• 分子量: 203.238
• InChiKey: VAJIQEORJZUVIB-KZVJFYERSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  84.2
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  L-山梨糖 在 吡啶 、 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 盐酸 、 20% palladium hydroxide-activated charcoal 、 盐酸羟胺 、 水 、 氢气 、 zinc trifluoromethanesulfonate 、 sodium hydride 、 potassium carbonate 、 溶剂黄146 、 triphenylphosphine dibromide 1:1 addition complex 、 三乙胺 、 乙酰氯 、 potassium iodide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， -78.0~110.0 ℃ 、500.01 kPa 条件下， 反应 224.5h， 生成 (6S,7R,8R,8aS)-8a-(hydroxymethyl)-octahydroindolizine-6,7,8-triol
  参考文献：
  名称：

  Hydroxymethyl-Branched Polyhydroxylated Indolizidines: Novel Selective α-Glucosidase Inhibitors

  摘要：

  alpha alpha-Disubstituted piperidines and conformationally constrained polyhydroxylated indolizidines bearing a hydroxymethyl substituent in position 8a were synthesized from a readily available L-sorbose-derived ketonitrone. Diastereoselective vinylation under two sets of complementary conditions allowed access to both configurations of the newly formed quaternary stereocenter. Subsequent N-allylation and ring-closing metathesis afforded 8a-branched indolizidines in high yield. The newly prepared iminosugars demonstrated highly potent inhibition of alpha-glucosidases. Most interestingly, compound 9b exhibits very high selectivity toward this class of enzymes, with an unusual mode of binding.

  DOI：

  10.1021/acs.orglett.5b01505

文献信息

• Quaternary Indolizidine and Indolizidone Iminosugars as Potential Immunostimulating and Glycosidase Inhibitory Agents: Synthesis, Conformational Analysis, Biological Activity, and Molecular Docking Study
  作者：Nitin J. Pawar、Vijay Singh Parihar、Ayesha Khan、Rakesh Joshi、Dilip D. Dhavale

  DOI：10.1021/acs.jmedchem.5b00951

  日期：2015.10.8

  reaction pathway. The conformations (5C8 or 8C5) of 1–3 were assigned on the basis of the 1H NMR studies. All compounds were found to be potent inhibitors of various glycosidase enzymes with Ki and IC50 values in the micromolar/nanomolar concentration range and further substantiated by molecular docking studies. The effect of synthesized iminosugars 1–3 on the cytokine secretion of IL-4, IL-6, and IFN-γ

  新季吲哚里的亚氨基糖，具有羟甲基在环交界处，即，C-8A-羟甲基-1- deoxycastanospermine同源1A，2A，3A和它们的3-氧代类似物1B，2B，和图3b通过使用分子内还原aminocyclization合成/的内酰胺d甘露糖/ d -葡萄糖衍生的C5-γ叠氮基酯作为关键步骤，其中所述吲哚里骨架的两个环都以一个锅煮以下级联反应路径建立。构象（5 ç 8或8 Ç 5）的1 -在1 H NMR研究的基础上分配了3个。发现所有化合物都是各种糖苷酶的有效抑制剂，其K i和IC 50值在微摩尔/纳摩尔浓度范围内，并通过分子对接研究进一步证实。合成的亚氨基糖的影响1 - 3对IL-4，IL-6和IFN-γ的细胞因子的分泌进行评价。发现所有化合物的T H1偏倚均会增加T H1 / T H2细胞因子比率（IL-6和IL-4）表明它们作为免疫刺激剂的功效。我们的研究表明，吲哚izidin
• Hydroxymethyl-Branched Polyhydroxylated Indolizidines: Novel Selective α-Glucosidase Inhibitors
  作者：Julien Boisson、Amélia Thomasset、Emilie Racine、Pascale Cividino、Thomas Banchelin Sainte-Luce、Jean-François Poisson、Jean-Bernard Behr、Sandrine Py

  DOI：10.1021/acs.orglett.5b01505

  日期：2015.8.7

  alpha alpha-Disubstituted piperidines and conformationally constrained polyhydroxylated indolizidines bearing a hydroxymethyl substituent in position 8a were synthesized from a readily available L-sorbose-derived ketonitrone. Diastereoselective vinylation under two sets of complementary conditions allowed access to both configurations of the newly formed quaternary stereocenter. Subsequent N-allylation and ring-closing metathesis afforded 8a-branched indolizidines in high yield. The newly prepared iminosugars demonstrated highly potent inhibition of alpha-glucosidases. Most interestingly, compound 9b exhibits very high selectivity toward this class of enzymes, with an unusual mode of binding.

表征谱图