t-butyl (3R)-3-[(t-butyldiphenylsilyl)oxy]-3,6-dihydropyridine-1(2H)-carboxylate | 804500-78-5

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: t-butyl (3R)-3-[(t-butyldiphenylsilyl)oxy]-3,6-dihydropyridine-1(2H)-carboxylate
• 英文别名: (R)-N-tert-butoxycarbonyl-5-(tert-butyldiphenylsilyloxy)-3-piperidene；tert-butyl (3R)-3-[tert-butyl(diphenyl)silyl]oxy-3,6-dihydro-2H-pyridine-1-carboxylate
• CAS: 804500-78-5
• 化学式: C₂₆H₃₅NO₃Si
• 分子量: 437.654
• InChiKey: USKNCJRUGFEALB-OAQYLSRUSA-N

物化性质

• 沸点：
  483.3±45.0 °C(Predicted)
• 密度：
  1.08±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.74
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  t-butyl (3R)-3-[(t-butyldiphenylsilyl)oxy]-3,6-dihydropyridine-1(2H)-carboxylate 在 碳酸氢钠 Oxone 、 1,1,1-三氟丙酮 、 三氟化硼乙醚 、 edetate disodium 作用下， 以 乙醚 、 乙腈 为溶剂， 反应 2.0h， 生成 (3S,4S,5R)-N-tert-butoxycarbonyl-3-(tert-butyldiphenylsilyloxy)-4-hydroxy-5-methylpiperidine
  参考文献：
  名称：

  N -Boc -5-羟基-3-哌啶烯作为常见结构单元的多种1-氮杂糖的新途径

  摘要：

  描述了一种合成具有异头位置氮原子的各种1-氮杂双胍的新的通用方法。易于获得的手性N -Boc-5-羟基-3-哌啶3通过立体选择性环氧化和区域选择性环裂解，以高度立体可控的方式转化为异黄花碱（2），高异黄花碱（13）和5'-脱氧异黄花碱（14）。 。此外，3,4,5- trihydroxypiperidines（所有四种立体异构体的合成18 - 21）被划分为1-azasugar型葡糖苷酶抑制剂是立体选择性地从（手性）啶实现3。

  DOI：

  10.1021/jo050519j
• 作为产物：
  描述：

  (R)-N-tert-butoxycarbonyl-5-acetoxy-3-piperidene 在 咪唑 、 4-二甲氨基吡啶 、 phosphate buffer 、 Pseudomonas cepacia lipase 、 ceramics 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 21.0h， 生成 t-butyl (3R)-3-[(t-butyldiphenylsilyl)oxy]-3,6-dihydropyridine-1(2H)-carboxylate
  参考文献：
  名称：

  N -Boc -5-羟基-3-哌啶烯作为常见结构单元的多种1-氮杂糖的新途径

  摘要：

  描述了一种合成具有异头位置氮原子的各种1-氮杂双胍的新的通用方法。易于获得的手性N -Boc-5-羟基-3-哌啶3通过立体选择性环氧化和区域选择性环裂解，以高度立体可控的方式转化为异黄花碱（2），高异黄花碱（13）和5'-脱氧异黄花碱（14）。 。此外，3,4,5- trihydroxypiperidines（所有四种立体异构体的合成18 - 21）被划分为1-azasugar型葡糖苷酶抑制剂是立体选择性地从（手性）啶实现3。

  DOI：

  10.1021/jo050519j

文献信息

• Conversion of chiral unsaturated cyanohydrins into chiral carba- and heterocycles via ring-closing metathesis
  作者：Adrianus M.C.H. van den Nieuwendijk、Amar B.T. Ghisaidoobe、Herman S. Overkleeft、Johannes Brussee、Arne van der Gen

  DOI：10.1016/j.tet.2004.07.103

  日期：2004.11

  Aliphatic unsaturated cyanohydrins 1-3 served as starting materials in the synthesis of a set of new chiral unsaturated cyclic 1,2-ethanolamines. Combining a Grignard addition-NaBH4 reduction sequence with a ring-closing metathesis afforded unsaturated cyclic 1,2-ethanolamines 7-11 and 22-25 in good yields and high ee (96-99%). The conversion of cyanohydrins 1-3 via a DIBAL reduction-transimination-NaBH4 reduction sequence, using allylamine, followed by ring-closing metathesis yielded tetrahydropyridines 28, tetrahydroazepinols 33 and tetrahydroazocinols 34 in high yields and excellent ee (97-99%). (C) 2004 Elsevier Ltd. All rights reserved.
• A short and concise synthesis of isofagomine, homoisofagomine, and 5′-deoxyisofagomine
  作者：Hidekazu Ouchi、Yukiko Mihara、Hitomi Watanabe、Hiroki Takahata

  DOI：10.1016/j.tetlet.2004.07.127

  日期：2004.9

  A short and concise synthesis of isofagomine derivatives via the epoxidation of chiral N-Boc-5-hydroxy-3-piperidene, followed by regioselective epoxide ring opening is described. This constitutes the first reported synthesis of homoisofagomine and the 5'-deoxyisofagomine. (C) 2004 Elsevier Ltd. All rights reserved.
• A New Route to Diverse 1-Azasugars from <i>N</i>-Boc-5-hydroxy-3-piperidene as a Common Building Block
  作者：Hidekazu Ouchi、Yukiko Mihara、Hiroki Takahata

  DOI：10.1021/jo050519j

  日期：2005.6.1

  for the synthesis of a variety of 1-azasugars with a nitrogen atom at the anomeric position is described. The readily available chiral N-Boc-5-hydroxy-3-piperidene 3 is transformed to isofagomine (2), homoisofagomine (13), and 5‘-deoxyisofagomine (14) via stereoselective epoxidation and regioselective ring-cleavage in a highly stereocontrolled manner. In addition, the synthesis of all four stereoisomers

  描述了一种合成具有异头位置氮原子的各种1-氮杂双胍的新的通用方法。易于获得的手性N -Boc-5-羟基-3-哌啶3通过立体选择性环氧化和区域选择性环裂解，以高度立体可控的方式转化为异黄花碱（2），高异黄花碱（13）和5'-脱氧异黄花碱（14）。 。此外，3,4,5- trihydroxypiperidines（所有四种立体异构体的合成18 - 21）被划分为1-azasugar型葡糖苷酶抑制剂是立体选择性地从（手性）啶实现3。
• Docking and SAR studies of d- and l-isofagomine isomers as human β-glucocerebrosidase inhibitors
  作者：Atsushi Kato、Saori Miyauchi、Noriko Kato、Robert J. Nash、Yuichi Yoshimura、Izumi Nakagome、Shuichi Hirono、Hiroki Takahata、Isao Adachi

  DOI：10.1016/j.bmc.2011.04.011

  日期：2011.6

  We report the structure-activity relationship of a series of D-, and L-isofagomine and fagomine isomers as glycosidase inhibitors. Our study revealed that a positive charge at the anomeric position of D-isofagomines enhanced the potency toward beta-glycosidases, while the epimerization at the C3 OH group drastically reduced their inhibitory potency by over three orders of magnitude. Furthermore, D-3,4-di-epi-isofagomine abolished their inhibition activities against all enzymes. L-Isofagomine was also a fairly potent inhibitor of human beta-glucocerebrosidase, with an IC50 value of 8.7 mu M. A molecular docking study revealed that the positions and orientations of the piperidine ring of D-3-epi-isofagomine in the binding site was similar to that of D-isofagomine, while D-3-epi-isofagomine missed the hydrogen bond interactions between Asp127 and the 3-OH group and between Trp179 and the 3-OH group. Furthermore, the top 10 docking models ranked by IFDscore suggested that D-3,4-di-epi-isofagomine can not bind to beta-glucocerebrosidase at a stable interaction mode. These results provide an insight into the structural requirements of isofagomine isomers for developing a new type of pharmacological chaperone for Gaucher disease. (C) 2011 Elsevier Ltd. All rights reserved.