[(8R,9S)-8-amino-1,4-dioxaspiro[4.5]decan-9-yl]methanol

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [(8R,9S)-8-amino-1,4-dioxaspiro[4.5]decan-9-yl]methanol
• 化学式: C₉H₁₇NO₃
• 分子量: 187.239
• InChiKey: PUHIJRJDEOGGNZ-HTQZYQBOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.15
• 重原子数：
  13.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  64.71
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  [(8R,9S)-8-amino-1,4-dioxaspiro[4.5]decan-9-yl]methanol 在 1-氯-N,N,2-三甲基丙烯胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 N-[(4'aS,8'aR)-spiro[1,3-dioxolane-2,6'-4,4a,5,7,8,8a-hexahydro-3,1-benzothiazine]-2'-yl]benzamide
  参考文献：
  名称：

  Preparation and biological evaluation of conformationally constrained BACE1 inhibitors

  摘要：

  The BACE1 enzyme is a key target for Alzheimer's disease. During our BACE1 research efforts, fragment screening revealed that bicyclic thiazine 3 had low millimolar activity against BACE1. Analysis of the co-crystal structure of 3 suggested that potency could be increased through extension toward the S3 pocket and through conformational constraint of the thiazine core. Pursuit of S3-binding groups produced low micromolar inhibitor 6, which informed the S3-design for constrained analogs 7 and 8, themselves prepared via independent, multi-step synthetic routes. Biological characterization of BACE inhibitors 6-8 is described. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.04.062
• 作为产物：
  描述：

  ethyl 8-hydroxy-1,4-dioxaspiro[4.5]dec-7-ene-7-carboxylate 在 platinum(IV) oxide 、 lithium aluminium tetrahydride 、 ytterbium(III) triflate hydrate 、 5%-palladium/activated carbon 、 氢气 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醇 、 甲基叔丁基醚 、 甲苯 为溶剂， 20.0 ℃ 、1.83 MPa 条件下， 反应 36.0h， 生成 [(8R,9S)-8-amino-1,4-dioxaspiro[4.5]decan-9-yl]methanol
  参考文献：
  名称：

  Preparation and biological evaluation of conformationally constrained BACE1 inhibitors

  摘要：

  The BACE1 enzyme is a key target for Alzheimer's disease. During our BACE1 research efforts, fragment screening revealed that bicyclic thiazine 3 had low millimolar activity against BACE1. Analysis of the co-crystal structure of 3 suggested that potency could be increased through extension toward the S3 pocket and through conformational constraint of the thiazine core. Pursuit of S3-binding groups produced low micromolar inhibitor 6, which informed the S3-design for constrained analogs 7 and 8, themselves prepared via independent, multi-step synthetic routes. Biological characterization of BACE inhibitors 6-8 is described. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.04.062